This page is no longer updated. Please seeThe COVID-19 Vaccine Delivery Partnership.
TheThe COVID-19 Vaccine Delivery Partnershipbuilds on the substantial body of work realized by the Country Readiness and Delivery (CRD) workstream that was part of COVAX since early 2020, and which made available global guidance and coordinated technical support for the implementation of COVID-19 vaccines.
The Country Readiness and Delivery (CRD) workstream was part of COVAX, the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator. Through the CRD workstream, WHO, UNICEF, the GAVI Secretariat, and partners worked together at the global and regional levels to develop and disseminate adaptable global resources (e.g., guidance, trainings, tools, and communication materials) and coordinate and provide technical assistance to support the implementation of COVID-19 vaccines. The CRD also collaborated closely across the ACT Accelerator to promote a cohesive approach to COVID-19 vaccination.
Please access the COVID-19 vaccine introduction toolbox (linked below) for guidance. These resources can help governments, health workers, and partners to design a range of strategies to increase the uptake of COVID-19 vaccination.
COVID-19 vaccines
Last updated: 20 July 2022
Since the start of the COVID-19 outbreak, WHO has worked with countries and areas in the Western Pacific Region on public health measures to slow or stop the spread of the virus.
Safe and effective vaccines are an important tool, in combination with other measures, to protect people against COVID-19, save lives and reduce widescale social disruption.
Countries and areas in the Western Pacific Region have already completed regulatory approval and started introducing one or more COVID-19 vaccines.
Through the COVAX Global Vaccine Facility and other mechanisms, WHO and partners are working with governments to facilitate equitable access to and distribution of an initial allocation of vaccine as quickly as possible.
WHO recommends that initial vaccination should prioritize groups at highest risk of exposure to infection in each country, including health workers, older persons and those with other health issues. Once COVID-19 vaccines reach priority groups, countries should vaccinate other priority groups and the general population.
It is important to get vaccinated as soon as it’s your turn and continue practicing other protective measures.
World health organization vaccines covid
English version last updated on 13 April 2022.
Safe and effective vaccines are available that provide strong protection against serious illness, hospitalization and death from COVID-19. Billions of people have been vaccinated against COVID-19. Getting vaccinated is one of the most important things you can do to protect yourself against COVID-19, help end the pandemic and stop new variants emerging.
Take all COVID-19 vaccine doses recommended to you by your health authority as soon as it is your turn, including a booster dose if recommended.
It is still possible to get COVID-19 and spread it to others after being vaccinated, so continue to do everything you can to keep yourself and others healthy. Continue keeping a safe distance from others and avoiding crowds, wearing a well-fitting mask covering your mouth and nose, keeping indoor spaces well ventilated, cleaning hands regularly and covering coughs and sneezes. If you do get COVID-19 after vaccination, you are more likely to have mild or no symptoms than if you hadn’t been vaccinated.
As of 8 April 2022, WHO has evaluated that the following vaccines against COVID-19 have met the necessary criteria for safety and efficacy:
Read our Q&A on the Emergency Use Listing process to find out more about how WHO assesses the quality, safety and efficacy of COVID-19 vaccines.
Some national regulators have also assessed other COVID-19 vaccine products for use in their countries.
Take whatever vaccine is made available to you first, even if you have already had COVID-19. It is important to be vaccinated as soon as possible once it’s your turn and not wait. It is safe and effective to mix-and-match different COVID-19 vaccines.
The current COVID-19 vaccines provide strong protection against serious illness and death caused by the Omicron and Delta variants of the virus that causes COVID-19. Being fully vaccinated will also help reduce the likelihood of new variants emerging.
For more information on booster doses and mixing-and-matching vaccines please read our COVID-19 Vaccines Q&A and COVID-19 Vaccines Safety Q&A.
WHO SHOULD GET VACCINATED
COVID-19 vaccines with WHO EUL are safe for most people 18 years and older, including those with pre-existing conditions, including auto-immune disorders. These conditions include: hypertension, diabetes, asthma, pulmonary, liver and kidney disease, as well as chronic infections that are stable and controlled.
If you are pregnant, want to get pregnant in the future or are currently breastfeeding, getting vaccinated is important to protect you and your current or future family. Many people around the world have now been vaccinated against COVID-19 while pregnant or breastfeeding, and no safety concerns have been identified for them or their babies. In fact, getting vaccinated while pregnant helps to protect your baby; this may also be the case if you get vaccinated while breastfeeding. You should still get vaccinated if you are menstruating on the day of your appointment.
If you are immunocompromised, you should be prioritised for an additional dose of COVID-19 vaccine after 1 to 3 months. People with compromised immune systems don’t always develop sufficient immunity against COVID-19 after one or two doses, so an additional dose can help to protect them. You should also get a booster dose if recommended.
There is growing evidence that children can be safely vaccinated against COVID-19. Check the COVID-19 vaccines Q&A page or the information pages on each vaccine for advice on what age-specific guidance is in place for that vaccine.
WHO SHOULD NOT GET VACCINATED
It is safe for most people to get vaccinated against COVID-19.
However, you should not be vaccinated if:
You have a history of severe allergic reactions/anaphylaxis to any of the ingredients of the COVID-19 vaccine, in order to avoid possible adverse effects.
You have a fever over 38.5ºC on the day of your vaccine appointment. Postpone until you have recovered.
You currently have confirmed or suspected COVID-19. Wait until you have completed the mandated isolation period and your acute symptoms have passed to get vaccinated.
If you are on blood thinners, it is safe for you to get vaccinated but let the person vaccinating you know.
WHAT TO EXPECT AFTER GETTING VACCINATED
Some people will experience mild side effects after being vaccinated against COVID-19. Common side effects to COVID-19 vaccines include a fever, head or body aches and a sore arm. These symptoms usually go away within a day or two. You can manage any side effects with rest, plenty of non-alcoholic liquids and taking medication to manage pain and fever, if needed. We do not recommend taking medication for pain before being vaccinated, as we don’t know how this will affect how well the vaccine works.
Contact your health care provider if you are worried about any of the side effects that you are experiencing. More serious or long-lasting side effects to COVID-19 vaccines are extremely rare. If you experience difficulty breathing, chest pain, confusion, loss of speech or mobility after your vaccine, contact your healthcare provider immediately. Vaccines are continually monitored to detect and respond to rare adverse events.
It takes several weeks after each dose of COVID-19 vaccine for your body to develop maximum levels of immunity – you are not protected right away. We still don’t know exactly how long protection from COVID-19 vaccines lasts, but most people have strong protection against serious illness and death for at least 6 months.
As WHO understands more about COVID-19 vaccines, we will be updating our recommendations accordingly and keeping the information on this page updated.
Have more questions about getting vaccinated against COVID-19? Check out the answers to the most frequently asked questions in the Q&As below.
Coronavirus disease (COVID-19): Vaccine research and development
Reviewed and current on 10 August 2021.
WHO and its partners are committed to accelerating the development of COVID-19 vaccines while maintaining the highest standards on safety.
Vaccines go through various phases of development and testing – there are usually three phases to clinical trials, with the last one designed to assess the ability of the product to protect against disease, which is called efficacy. All phases assess safety. The last phase, phase III, are usually conducted in a large number of people, often 10’s of thousands. After that, the vaccine needs to go through a review by the national regulatory authority, who will decide if the vaccine is safe and effective enough to be put on the market, and a policy committee, who will decide how the vaccine should be used.
In the past, vaccines have been developed through a series of consecutive steps that can take many years. Now, given the urgent need for COVID-19 vaccines, unprecedented financial investments and scientific collaborations are changing how vaccines are developed. This means that some of the steps in the research and development process have been happening in parallel, while still maintaining strict clinical and safety standards. For example, some clinical trials are evaluating multiple vaccines at the same time. It is the scale of the financial and political commitments to the development of a vaccine that has allowed this accelerated development to take place. However, this does not make the studies any less rigorous.
The more vaccines in development the more opportunities there are for success.
Any longer-term safety assessment will be conducted through continued follow up of the clinical trial participants, as well as through specific studies and general pharmacovigilance of those being vaccinated in the roll out. This represents standard practise for all newly authorized vaccines.
More information about COVID-19 vaccine development is available here.
In a regular vaccine study, one group of volunteers at risk for a disease is given an experimental vaccine, and another group is not; researchers monitor both groups over time and compare outcomes to see if the vaccine is safe and effective.
In a human challenge vaccine study, healthy volunteers are given an experimental vaccine, and then deliberately exposed to the organism causing the disease to see if the vaccine works. Some scientists believe that this approach could accelerate COVID-19 vaccine development, in part because it would require far fewer volunteers than a typical study.
However, there are important ethical considerations that must be addressed – particularly for a new disease like COVID-19, which we do not yet fully understand and are still learning how to treat; it may be difficult for the medical community and potential volunteers to properly estimate the potential risks of participating in a COVID-19 human challenge study. For more information, see this WHO publication on the ethics of COVID-19 human challenge studies.
Small (phase I) safety studies of COVID-19 vaccines should enroll healthy adult volunteers. Larger (phase II and III) studies should include volunteers that reflect the populations for whom the vaccines are intended. This means enrolling people from diverse geographic areas, racial and ethnic backgrounds, genders, and ages, as well as those with underlying health conditions that put them at higher risk for COVID-19. Including these groups in clinical trials is the only way to make sure that a vaccine will be safe and effective for everyone who needs it.
Opportunities to volunteer for a COVID-19 vaccine trial vary from country to country. If you are interested in volunteering, check with local health officials or research institutions or email [email protected] for more information about vaccine trials.
Getting the COVID-19 Vaccine
This article is part of a series of explainers on vaccine development and distribution. Learn more about vaccines – from how they work and how they’re made to ensuring safety and equitable access – in WHO’s Vaccines Explained series.
Vaccines are a critical tool in the battle against COVID-19, and getting vaccinated is one of the best ways to protect yourself and others from COVID-19.
Getting vaccinated is safer than getting infected
Vaccines train our immune system to recognize the targeted virus and create antibodies to fight off the disease without getting the disease itself. After vaccination, the body is ready to fight the virus if it is later exposed to it, thereby preventing illness.
Most people who are infected with SARS-CoV-2, the virus that causes COVID-19, develop an immune response within the first few weeks, but we are still learning how strong and lasting that immune response is, and how it varies between different people.
People who have already been infected with SARS-CoV-2 should still get vaccinated unless told otherwise by their health care provider. Even if you’ve had a previous infection, the vaccine acts as a booster that strengthens the immune response. There have also been some instances of people infected with SARS-CoV-2 a second time, which makes getting vaccinated even more important.
What to expect during vaccination
Medical professionals can best advise individuals on whether or not, and when, they should receive a vaccine. A health worker will administer the vaccine, and the person receiving it will be asked to wait for 15–30 minutes before leaving the vaccination site. This is so that health workers can observe individuals for any unexpected reactions following vaccination.
Like any vaccine, COVID-19 vaccines can cause mild-to-moderate side effects, such as a low-grade fever or pain or redness at the injection site. These should go away on their own within a few days. See WHO’s Safety of COVID-19 Vaccines explainer and Vaccines Safety Q&A to learn more about common side effects and find out who should consult with a doctor before vaccination.
Vaccine doses
For some COVID-19 vaccines, two doses are required. It’s important to get the second dose if the vaccine requires two doses.
For vaccines that require two doses, the first dose presents antigens – proteins that stimulate the production of antibodies – to the immune system for the first time. Scientists call this priming the immune response. The second dose acts as a booster, ensuring the immune system develops a memory response to fight off the virus if it encounters it again.
Because of the urgent need for a COVID-19 vaccine, initial clinical trials of vaccine candidates were performed with the shortest possible duration between doses. Therefore an interval of 21–28 days (3–4 weeks) between doses is recommended by WHO. Depending on the vaccine, the interval may be extended for up to 42 days – or even up to 12 weeks for some vaccines – on the basis of current evidence.
There are many COVID-19 vaccines being developed and produced by different manufacturers around the world. WHO recommends that a vaccine from the same manufacturer be used for both doses if you require two doses. This recommendation may be updated as further information becomes available.
Safety against infection and transmission after vaccination
Available clinical trials have shown COVID-19 vaccines to be safe and highly effective at preventing severe disease. Given how new COVID-19 is, researchers are still looking into how long a vaccinated person is likely to be protected from infection, and whether vaccinated people can still transmit the virus to others. As the vaccine rollout expands, WHO will continue to monitor the data alongside regulatory authorities.
Safe and effective vaccines are making a significant contribution to preventing severe disease and death from COVID-19. As vaccines are rolling out and immunity is building, it is important to continue to follow all of the recommended measures that reduce the spread of SARS-CoV-2. This includes physically distancing yourself from others; wearing a mask, especially in crowded and poorly ventilated settings; cleaning your hands frequently; covering any cough or sneeze in your bent elbow; and opening windows when indoors.
Coronavirus disease (COVID-19): Vaccines
There are several COVID-19 vaccines validated for use by WHO (given Emergency Use Listing). The first mass vaccination programme started in early December 2020 and the number of vaccination doses administered is updated on a daily basis on the COVID-19 dashboard.
The WHO Emergency Use Listing process determines whether a product can be recommended for use based on all the available data on safety and efficacy and on its suitability in low- and middle-income countries. Vaccines are assessed to ensure they meet acceptable standards of quality, safety and efficacy using clinical trial data, manufacturing and quality control processes. The assessment weighs the threat posed by the emergency as well as the benefit that would accrue from the use of the product against any potential risks.
In line with their national regulations and legislation, countries have the autonomy to issue emergency use authorizations for any health product. Domestic emergency use authorizations are issued at the discretion of countries and not subject to WHO approval.
As of 12 January 2022, the following vaccines have obtained EUL:
Getting vaccinated could save your life. COVID-19 vaccines provide strong protection against serious illness, hospitalization and death. There is also some evidence that being vaccinated will make it less likely that you will pass the virus on to others, which means your decision to get the vaccine also protects those around you.
Even after getting vaccinated, keep taking precautions to protect yourself, family, friends and anyone else you may come into contact with. COVID-19 vaccines are highly effective, but some people will still get ill from COVID-19 after vaccination. There is also still a chance that you could also pass the virus on to others who are not vaccinated. Stay at least 1 metre away from other people, wear a properly fitted mask over your nose and mouth when you can’t keep this distance, avoid poorly ventilated places and settings, clean your hands frequently, stay home if unwell and get tested, and stay informed about how much virus is circulating in the areas where you travel, live and work.
WHO recommends that while vaccine supply is limited, the people at highest risk of COVID-19 are vaccinated first. This includes people who are more likely to get severe disease if they are infected (older persons and people with existing health conditions) and people who are more likely to be exposed to the virus (such as health workers). People who are pregnant have a higher risk of serious illness and preterm birth if they are infected with COVID-19, so WHO recommends that they are also prioritized for vaccination, once the first priority groups have been vaccinated.
If you live in a country where vaccines are available to more people beyond these priority groups, get vaccinated as soon as it is your turn.
WHO-authorized COVID-19 vaccines are safe for most people of 18 years and older, including those with pre-existing conditions of any kind such as auto-immune disorders. These conditions include hypertension, diabetes, asthma, pulmonary, liver and kidney disease, as well as chronic infections that are stable and controlled.
The Pfizer vaccine can be safely administered to children from 5 years of age. Both Moderna and Pfizer vaccines are licensed for use in children from 12 years of age.
Vaccine trials for the use of other COVID-19 vaccines in children and adolescents are ongoing and WHO will update its recommendations when the evidence or epidemiological situation justifies a change in policy.
Children and adolescents above 5 years of age with comorbidities that put them at significantly higher risk of serious COVID-19 may be offered vaccination alongside other high priority groups.
However, WHO recommends that countries should vaccinate healthy children only when high vaccine coverage with two doses has been achieved in higher priority-use groups, as identified in the WHO Prioritization Roadmap.
There are very few conditions that would exclude someone from being vaccinated, but you should NOT be vaccinated if:
COVID-19 vaccines are safe for people taking blood thinners, but you should let the person giving you the vaccine know about any medication you are taking BEFORE you are given the vaccine.
In addition to the general recommendations above, each vaccine may have specific considerations for specific populations and health conditions. Talk to your doctor for advice about your specific situation.
Yes. Even if you have already had COVID-19, you should be vaccinated. The protection that someone gains from having COVID-19 will vary greatly from person to person. The immunity people get from being vaccinated after having a natural infection is consistently very strong. Getting vaccinated even if you have had COVID-19 means you are more likely to be protected for longer.
There is currently no evidence to determine the optimal time that you should wait to be vaccinated after having COVID-19. Persons with laboratory-confirmed COVID-19 infection can consider delaying vaccination for 6 months based on the fact that natural infection leads to some protection against infection. Ask your health worker for advice.
All vaccines with WHO Emergency Use Listing are highly effective at preventing serious illness, hospitalization and death due to COVID-19. You should accept the vaccine you are offered first and get vaccinated as soon as it is your turn to reduce your risk.
Do not delay getting vaccinated, unless advised to by your health care provider, as this could put you at risk of COVID-19. Getting vaccinated could save your life.
In April 2020, WHO published the minimum criteria for how effective COVID-19 vaccines should be to make them useful for fighting COVID-19. All current vaccines authorized by WHO meet these criteria. To fully understand how effective different vaccines are, we need more real world data. This will come as more people are vaccinated.
The best COVID-19 vaccine is the one available to you soonest.
Read more on the different types of COVID-19 vaccines. You can also learn about the individual COVID-19 vaccines on our information pages for the different vaccines: AstraZeneca, Covaxin, Sinovac, Sinopharm, Johnson and Johnson (J&J) Janssen, Moderna, Pfizer.
COVID-19 vaccines are an important tool to stop the pandemic, but they will not do so on their own. Public health and social measures such as surveillance, contact tracing, isolation and individual protective behaviours such as staying at least 1 metre away from other people, wearing a properly fitted mask over your nose and mouth, avoiding poorly ventilated places and settings, staying home if unwell, covering coughs and sneezes and cleaning your hands frequently remain essential to breaking the chain of transmission.
The impact of COVID-19 vaccines on the pandemic will depend on several factors. These include the effectiveness of the vaccines; how quickly they are approved, manufactured, and delivered; the possible development of other variants, and how many people get vaccinated.
We are still learning about how long immunity to COVID-19 lasts from natural infection, and from vaccination. We are now starting to see evidence that the immunity you get after having COVID-19 can be strong. However, the type of immunity that’s developed after infection varies from person to person, making it less predictable than immunity after vaccination. Scientists are working hard to understand this better.
What we do know is that COVID-19 is a life-threatening disease that can have long-term consequences. We also know that the WHO-authorised COVID-19 vaccines have been safely given to billions of people. It is much safer to get vaccinated than it is to risk getting COVID-19. Get vaccinated as soon as it’s your turn and keep doing everything you can to protect yourself and others.
As we learn more about COVID-19 and immunity, WHO continues to update our guidance and recommendations.
The COVID-19 vaccines with WHO Emergency Use Listing (EUL) provide different levels of protection to infection, mild disease, severe disease, hospitalization and death. Research is ongoing by thousands of scientists around the world to better understand how new virus mutations and variants affect the effectiveness of the different COVID-19 vaccines.
In general, the COVID-19 vaccines are very effective at preventing serious illness, hospitalization and death from all current virus variants. They are less effective at protecting you against infection and mild disease than they were for earlier virus variants; but if you do get ill after being vaccinated, your symptoms are more likely to be mild.
Remember that while the COVID-19 vaccines authorised by WHO are incredibly effective at reducing your risk of developing serious illness and death, no vaccine is 100% effective. A small percentage of people will still get ill from COVID-19 even though they have been vaccinated. Currently there is limited information about the risk of vaccinated people passing the virus to others if they are infected. This makes it very important to continue to practice public health and social measures, even after you have been fully vaccinated.
Scientists around the world are continuing to develop many potential vaccines for COVID-19. These vaccines are all designed to teach the body’s immune system to safely recognize and block the virus that causes COVID-19.
Several different types of potential vaccines for COVID-19 have been developed, including:
It is safe and effective for you to receive a second or a third dose of a different COVID-19 vaccine. If you’re offered a different type of vaccine, you can go ahead and get vaccinated. WHO considers two doses of any WHO EUL vaccine to be a complete primary series, See the full list of COVID-19 vaccines with WHO EUL here.
By mixing and matching vaccines, countries are able to maximise vaccine impact in the event of constrained or limited supply.
People over 60 who have received two doses of Sinovac and Sinopharm should be given a third dose to restore waning immunity over time. WHO Strategic Advisory Group of Experts on Immunization (SAGE) has stated that Pfizer or AstraZeneca can also be used for the third dose, if the original vaccine is not available.
Like with any vaccine, some people will experience mild to moderate side effects after being vaccinated against COVID-19. This is a normal sign that the body is developing protection. Side effects to COVID-19 vaccines include a fever, tiredness, headache, muscle ache, chills, diarrhoea and pain or redness at the injection site. Not everyone will experience side effects. Most side effects go away within a few days on their own. You can manage any side effects with rest, plenty of non-alcoholic liquids and taking medication to manage pain and fever, if needed.
If you are worried that the side effects that you are experiencing are unusual, if the pain in the arm where you got the injection gets worse after 24 hours or your side effects don’t go away in a few days, contact your healthcare provider for advice.
More serious or long-lasting side effects to COVID-19 vaccines are possible but extremely rare. If you experience difficulty breathing, chest pain, confusion, loss of speech or mobility after your vaccine, contact your healthcare provider immediately. Vaccines are continually monitored for as long as they are in use to detect and respond to rare adverse events.
The vaccine stimulates your immune system to protect you from the virus. This process can sometimes cause side effects like fever, chills or headache, but not everyone will experiences any side effect. The presence or magnitude of the reaction you may have vaccination does not predict or reflect your immune response to the vaccine.
You do not have to have side effects in order to be protected.
If you are worried about your side effects, contact your healthcare provider and let them know about your recent vaccination.
In very rare cases, some people may experience an allergic reaction after being vaccinated against COVID-19. A severe allergic reaction – such as anaphylaxis – is a very rare side effect of any vaccine.
If you have a history of allergic reactions, talk to your healthcare provider before you get vaccinated. They will be able to give you advice. In some cases, precautions will need to be taken for people who have known allergies to previous doses of the vaccine or known components of the vaccine.
Healthcare workers administering COVID-19 vaccines should be trained to recognise and treat serious allergic reactions. This is why people being vaccinated against COVID-19 will be asked to stay at the vaccination site for a period of time following their injection, to ensure that anyone experiencing an allergic reaction can receive prompt treatment.
Reports of adverse events following COVID-19 vaccination (including allergic reactions) are closely monitored by national authorities and international bodies, including WHO for the early detection of serious side effects.
As with any vaccine, it is essential to closely monitor the safety and effectiveness of COVID-19 vaccines that are used in immunization programmes. If a serious health problem is reported following vaccination, a thorough investigation should take place by the public health programme in the country.
It is rare to find that health problems occurring following receipt of a vaccine are actually caused by the vaccine itself. Health problems following vaccination are most often found to be coincidental and entirely unrelated to vaccination. Sometimes they are related to how the vaccine has been stored, transported, or administered. Errors related to the delivery of the vaccine can be prevented by better training health workers and strengthening supply chains.
The results of the investigation will then inform next steps. The safety of COVID-19 vaccines is the top priority of the World Health Organization.
Yes. The maximum level of protection from COVID-19 vaccines is not reached until several weeks after full vaccination. If you have a two-dose vaccine, this means that you don’t get full immunity until 2 – 4 weeks after the second dose. You can still become infected and ill during this time.
While COVID-19 vaccines are highly effective against serious illness, hospitalisation and death, no vaccine is 100% effective. As a result, a number of vaccinated people will get infected and may fall ill with COVID-19 in spite of being fully vaccinated. This is known as a ‘breakthrough infection’ or ‘breakthrough case’. With more infectious virus variants such as Delta, we are seeing more breakthrough infections and cases.
Breakthrough infections can happen with every vaccine, and do not mean that the vaccine does not work. According to data from the US CDC, unvaccinated people are at 11 times the risk of death from COVID-19 than vaccinated people. People who get COVID-19 after being vaccinated are much more likely to only experience mild symptoms; efficacy against serious illness and death remains high. Get vaccinated, as soon as it’s your turn.
Even once you are fully vaccinated, continue to practice the same prevention measures to protect yourself. Stay at least 1 metre away from other people, wear a well fitted mask over your nose and mouth when you can’t keep this distance, avoid poorly ventilated places and settings, clean your hands frequently, stay home if unwell and get tested and stay informed about how much virus is circulating in the areas where you travel, live and work.
There is some evidence that being fully vaccinated can prevent infection with the COVID-19 virus. This means that being vaccinated is likely to help protect people around you by making it less likely that you will pick up the virus and pass it on.
Research is ongoing to understand the extent to which being vaccinated stops you from becoming infected and passing the virus on to others. More data is needed to know the extent of this protection. There is still a chance you could pass the virus on.
Even once you are fully vaccinated, continue to practice the same prevention measures to protect other people. Stay at least 1 metre away from other people, wear a properly fitted mask over your nose and mouth when you can’t keep this distance, avoid poorly ventilated places and settings, clean your hands frequently, stay home if unwell and get tested, and stay informed about how much virus is circulating in the areas where you travel, live and work.
No. Even after getting vaccinated, keep taking precautions to protect yourself, family and friends if there is still COVID-19 in your area.
The maximum level of protection is not reached until several weeks after full vaccination. If you have a two-dose vaccine, this means that you don’t get full immunity until 2–4 weeks after the second dose.
COVID-19 vaccines are highly effective, but a small percentage of people will still get ill from COVID-19 after vaccination (this is known as a breakthrough infection). There is also still a chance that you could pass the virus on to others who are not vaccinated. Some people have not been vaccinated against COVID-19, cannot be vaccinated, or do not develop full immunity in response to COVID-19 vaccines because of having a weakened immune system. Continue to practice all protective behaviours to protect yourself and others.
Even once you are fully vaccinated, stay at least 1 metre away from other people, wear a properly fitted mask over your nose and mouth when you can’t keep this distance, avoid poorly ventilated places and settings, clean your hands frequently, stay home if unwell and get tested, stay informed about how much virus is circulating in the areas where you travel, live and work, and get vaccinated as soon as it is your turn.
We still don’t know exactly how long protection from COVID-19 vaccines lasts, but current data indicates that most people have strong protection against serious illness and death for at least 6 months.
There is increasing evidence that the effectiveness of COVID-19 vaccine against infection and mild symptoms can wane over time. In light of this, WHO Strategic Advisory Group of Experts on Immunization (SAGE) has advised that booster doses are offered to people 4-6 months after the primary series of vaccination is completed. A booster dose should be taken when offered, to strengthen protection against serious illness and death from COVID-19.
Immunity may reduce faster in people who are older or who have underlying medical conditions, or who have a high level of exposure to the virus, so SAGE recommends that boosters are offered to higher priority-use groups before vaccines are given to those in lower-priority use groups.
People over 60 and immune-compromised who have received two doses of Sinovac and Sinopharm should also be given an additional third dose as part of the primary series to reach sufficient immunity. A booster dose is recommended for these vaccines, for more details consult the interim recommendations.
To protect yourself, get vaccinated AND continue practicing the recommended protective behaviours against COVID-19, including regular hand-washing, physical distancing, and ventilation of rooms.
People with compromised immune systems don’t always develop maximum immunity against COVID-19 after one or two doses, so may need an additional dose to protect them. WHO recommends that people who are moderately or severely immunocompromised should be offered an additional dose of COVID-19 vaccine.
For Sinovac and Sinopharm, WHO recommends that countries should consider offering a third dose of the vaccine to the vaccination schedule for those aged 60 and over as an extension of the primary series, once a high level of coverage of first and second doses has been achieved in the priority groups.
An additional dose is different from a booster dose. It is considered part of an extended primary series for people who do not develop sufficient protection after one or two doses. It is intended to help these individuals to develop better protection against COVID-19.
A booster dose is an extra dose of vaccine administered to a vaccinated person that has completed a primary vaccination series, (currently one, two or three doses of COVID-19 vaccine depending on the vaccine and the population group) when, with time, the immunity and clinical protection has fallen below a rate deemed sufficient in that population.
The protection you get from COVID-19 vaccines can wane over time, evidence shows that the effectiveness wanes around 4-6 months after the primary series of vaccination has been completed. If you are offered a booster you should take it to strengthen your protection against serious disease.
WHO currently recommends that individuals over the age of 18 have 1 booster dose 4-6 months after completing the primary series. WHO does not currently recommend that children and young adults under the age of 18 receive a booster dose.
SAGE recommends that high-priority use groups are offered boosters, prior to continuing the roll-out of primary vaccination among lower-priority use groups.
SAGE is reviewing the available data on the need for additional booster doses to maintain protection against COVID-19 and will update the recommendations accordingly.
No, the COVID-19 vaccine will not cause a positive test result for a COVID-19 PCR or antigen laboratory test. This is because the tests check for active disease and not whether an individual is immune. However, because the COVID-19 vaccine prompts an immune response, it may be possible to test positive in an antibody (serology) test that measures COVID-19 immunity in an individual.
You should follow national advice and the advice of the countries you are travelling to and from. Some countries are allowing fully vaccinated people to avoid quarantine and testing on arrival. This is because these individuals are at a lower risk of COVID-19 and are less likely to get infected and pass the virus to others. But even once you are fully vaccinated, continue to practice the same prevention measures – no vaccine is 100% effective, and doing it all helps protect yourself and others. Stay at least 1 metre away from other people, wear a properly fitted mask over your nose and mouth when you can’t keep this distance, avoid poorly ventilated places and settings, clean your hands frequently, stay home if unwell and get tested, and stay informed about how much virus is circulating in the areas where you travel, live and work.
WHO does not support using proof of vaccination as a requirement for international travel. This would not be fair, given that there are not enough vaccines for everyone, and that some countries have more access to vaccines than others.
There is no known influence or interaction between antibiotics and COVID-19 vaccines. If you are prescribed antibiotics by a health professional before or after your vaccination, you should go ahead and take the full course. However, if you have a temperature over 38.5 ºC at the time of your vaccination appointment, you should reschedule for when you feel better.
There is no evidence that the safety or effectiveness of COVID-19 vaccines is affected by anything you eat or drink before or after getting vaccinated, including alcohol. However, drinking alcohol can add to the normal mild to moderate side effects that you might experience after vaccination, such as a headache and tiredness. Because of this, it is advisable to avoid drinking until any side effects following vaccination have passed. Learn more about the side effects of COVID-19 vaccines.
While COVID-19 vaccines are highly effective at preventing serious illness and death, there is still a chance you could be infected after being vaccinated. Continue to protect yourself and others by continuing to practice physical distancing, wear a well-fitted mask over your nose and mouth, clean your hands frequently, stay home if you feel unwell, cover coughs and sneezes and keep indoor spaces well ventilated. Drinking alcohol may make you less vigilant in practicing these behaviours and so can put you and others at risk.
Please keep in mind that drinking alcohol can increase your risk of other health problems.
The Pfizer vaccine can be safely administered to children from 5 years of age. Both Moderna and Pfizer vaccines are licensed for use in children from 12 years of age.
WHO recommends that children aged 5 and above with comorbidities that put them at significant risk of severe COVID-19 should be offered vaccination, at a reduced dosage, alongside other high-risk groups.
Countries may now consider vaccinating healthy children from the age of 5 years of age and adolescents as part of their national vaccination strategies. However, WHO strongly recommends that countries should vaccinate children only when high vaccine coverage with primary vaccination series has been achieved in higher priority-use groups, as identified in the WHO Prioritization Roadmap.
Vaccine trials for children and adolescents and other COVID-19 vaccines are ongoing and WHO will update its recommendations when the evidence or epidemiological situation justifies a change in policy.
COVID-19 has also been a more serious and dangerous disease among older people. While the supply of vaccines is constrained, the ongoing priority is to vaccinate those most at risk of serious illness who still have not been vaccinated in many parts of the world: older people, those with chronic health conditions and health workers.
Most children are at low risk of serious disease and vaccinating them would be primarily about reducing transmission. There is emerging evidence that vaccines may be less effective at reducing transmission of Omicron. This means that the most impactful thing that can be done to protect children while vaccines are still being prioritised for those most at risk is to continue to practice the protective behaviours: keep a safe distance from others and avoid crowds, wear a well-fitting mask covering your mouth and nose, keep indoor spaces well ventilated, clean hands regularly and cover coughs and sneezes. Caregivers should follow national guidelines around children staying home from school if unwell, getting tested for COVID-19 when showing symptoms.
Yes, you can get vaccinated if you are pregnant. During pregnancy, you are at higher risk of serious illness caused by COVID-19. You are also at higher risk of delivering your baby prematurely if you contract COVID-19. While there is less data available on vaccination of pregnant people, evidence on the safety of COVID-19 vaccines during pregnancy has been growing, and no safety concerns have been identified. Especially in countries with high transmission, or if you have an occupation where you are at more risk of being exposed to COVID-19, the benefits of getting the vaccine outweigh potential risks. There is no risk of getting COVID-19 from the vaccine. Talk to your healthcare provider to make an informed decision about vaccination.
Yes, you should get vaccinated if you are planning to get pregnant. There is no current evidence that suggests the COVID-19 vaccines interfere with fertility. There is currently no biological evidence that antibodies from COVID-19 vaccination or vaccine ingredients could cause any problems with reproductive organs. Getting vaccinated is the best thing you can do to protect yourself and the future health of your baby.
If you are breastfeeding, you should get vaccinated against COVID-19 as soon as it is your turn. None of the current COVID-19 vaccines have live virus in them. This means there is no risk of you transmitting COVID-19 to your baby through your breastmilk from the vaccine. In fact, the antibodies you get after vaccination may go through your breast milk and help to protect your baby.
You should get vaccinated if you are menstruating. If you have your period on the day of your vaccination appointment, you can go ahead and get vaccinated. Menstruation isn’t a medical reason to not get the COVID-19 vaccine. If you have concerns or questions about your periods, do not hesitate to speak with your health care provider.
There have been some reports of people experiencing disruption to their menstrual cycle after being vaccinated against COVID-19. There is not yet enough data available to know whether there is a connection between the vaccines and this disruption. Several large studies researching the impact of vaccines on menstrual cycles are ongoing. WHO will continue to monitor any new evidence regarding menstrual cycles. Information regarding these studies can be found here and here.
If you have concerns or questions about your periods, do not hesitate to speak with a health care provider.
World health organization vaccines covid
The availability of a safe and effective vaccine for COVID-19 is well-recognized as an additional tool to contribute to the control of the pandemic. At the same time, the challenges and efforts needed to rapidly develop, evaluate and produce this at scale are enormous. It is vital that we evaluate as many vaccines as possible as we cannot predict how many will turn out to be viable.
To increase the chances of success (given the high level of attrition during vaccine development), we must test all candidate vaccines until they fail. WHO is working to ensure that all of them have the chance of being tested at the initial stage of development.
This is a major and extraordinary global research undertaking: WHO is facilitating collaboration and accelerated efforts on a scale not seen before; it is convening vital communications across the research community and beyond.
Key links
R&D Roadmap for COVID-19
Highlights of WHO actions so far
The 4 critical elements of WHO global R&D efforts in detail
1. Harnessing a broad global coalition to develop and evaluate candidate vaccines as quickly and safely as possible
WHO’s core function is to direct and coordinate international efforts through:
WHO is facilitating interactions between scientists, developers and funders to support coordination, and/or provide common platforms for working together. It is combining the relative strengths of different stakeholders. It has used its global mandate to rapidly convene 300 scientists, developers and funders to increase the likelihood that one or more safe and effective vaccines will soon be available to all. Activities are being delivered at extremely high speed with many steps executed simultaneously.
2. Mapping candidate vaccines and their progress across the world
Over 210 candidate vaccines are at some stage of development. Of these, at least 48 candidate vaccines are in human trial. About 10 are in phase III trials. There are several others currently in phase I/II, which will enter phase III in the coming months.
WHO is fostering regular open dialogue between researchers and vaccine developers to expedite the exchange of scientific results, debate concerns and propose rapid and robust methods for vaccine evaluation.
3. Defining the desired characteristics of safe and effective vaccines to combat the pandemic
To guide the efforts of vaccine developers, WHO has drawn up a Global Target Product Profile target product profiles (TPPs) for COVID-19.
This document outlines the minimum and desired attributes of safe and effective vaccines. The TPPs cover two types of vaccines: vaccines for the long-term protection of people at higher risk of COVID-19 such as healthcare workers; and vaccines for use in response to outbreaks with rapid onset of immunity.
WHO has also coordinated expert consultations to identify the potential role of different animal models and laboratory assays to evaluate and screen candidate vaccines before their evaluation in humans. We are devising an unprecedented effort for rapid assessment of many candidates simultaneously before they are tested in humans.
4. Coordinating clinical trials across the world – giving humanity the best chance of safe and effective vaccines for all
WHO is proposing to massively accelerate the evaluation of vaccines. Its expert group has designed a large international randomized controlled clinical trial to enable the simultaneous evaluation of the benefits and risks of different vaccines at sites with sufficiently high rates of the disease. This will ensure a faster turnaround of results.
The power of the vaccine Solidarity trial is its global ambition, and the potential to rapidly deploy and assess vaccines in areas with high transmission. The results for the efficacy of each vaccine are expected within three to six months and this evidence, combined with data on safety, will inform decisions about whether it can be used on a wider scale in those countries or regions where the vaccines are being tested.
WHO expert groups are also considering:
Side Effects of COVID-19 Vaccines
This article is part of a series of explainers on vaccine development and distribution. Learn more about vaccines – from how they work and how they’re made to ensuring safety and equitable access – in WHO’s Vaccines Explained series.
COVID-19 vaccines are safe, and getting vaccinated will help protect you against developing severe COVID-19 disease and dying from COVID-19. You may experience some mild side effects after getting vaccinated, which are signs that your body is building protection.
Why it’s normal to have mild side effects from vaccines
Vaccines are designed to give you immunity without the dangers of getting the disease. It’s common to experience some mild-to-moderate side effects when receiving vaccinations. This is because your immune system is instructing your body to react in certain ways: it increases blood flow so more immune cells can circulate, and it raises your body temperature in order to kill the virus.
Mild-to-moderate side effects, like a low-grade fever or muscle aches, are normal and not a cause for alarm: they are signs that the body’s immune system is responding to the vaccine, specifically the antigen (a substance that triggers an immune response), and is gearing up to fight the virus. These side effects usually go away on their own after a few days.
Common and mild or moderate side effects are a good thing: they show us that the vaccine is working. Experiencing no side effects doesn’t mean the vaccine is ineffective. It means everybody responds differently.
Common side effects of COVID-19 vaccines
Like any vaccine, COVID-19 vaccines can cause side effects, most of which are mild or moderate and go away within a few days on their own. As shown in the results of clinical trials, more serious or long-lasting side effects are possible. Vaccines are continually monitored to detect adverse events.
Reported side effects of COVID-19 vaccines have mostly been mild to moderate and have lasted no longer thana few days. Typical side effects include pain at the injection site, fever, fatigue, headache, muscle pain, chills and diarrhoea. The chances of any of these side effects occurring after vaccination differ according to the specific vaccine.
COVID-19 vaccines protect against the SARS-CoV-2 virus only, so it’s still important to keep yourself healthy and well.
Less common side effects
Upon receiving the vaccine, a person should be requested to stay for 15–30 minutes at the vaccination site so health workers are available in case of any immediate reactions. Individuals should alert their local health providers following vaccination if they experience any unexpected side effects or other health events – such as side effects lasting more than three days. Less common side effects reported for some COVID-19 vaccines have included severe allergic reactions such as anaphylaxis; however, this reaction is extremely rare.
National authorities and international bodies, including WHO, are closely monitoring for any unexpected side effects following COVID-19 vaccine use.
Long-term side effects
Side effects usually occur within the first few days of getting a vaccine. Since the first mass vaccination programme started in early December 2020, hundreds of millions of vaccine doses have been administered.
There have been concerns about COVID-19 vaccines making people sick with COVID-19. But none of the approved vaccines contain the live virus that causes COVID-19, which means that COVID-19 vaccines cannot make you sick with COVID-19.
After vaccination, it usually takes a few weeks for the body to build immunity against SARS-CoV-2, the virus that causes COVID-19. So it’s possible a person could be infected with SARS-CoV-2 just before or after vaccination and still get sick with COVID-19. This is because the vaccine has not yet had enough time to provide protection.
Experiencing side effects after getting vaccinated means the vaccine is working and your immune system is responding as it should. Vaccines are safe, and getting vaccinated will help protect you against COVID-19.
COVAX
Working for global equitable access to COVID-19 vaccines
No one is safe, until everyone is safe
COVAX is the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator. The ACT Accelerator is a ground-breaking global collaboration to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines.
COVAX is co-led by the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi and the World Health Organization (WHO), alongside key delivery partner UNICEF. In the Americas, the PAHO Revolving Fund is the recognized procurement agent for COVAX. It aims to accelerate the development and manufacture of COVID-19 vaccines and to guarantee fair and equitable access for every country in the world.
WHO has multiple roles within COVAX: It provides normative guidance on vaccine policy, regulation, safety, R&D, allocation, and country readiness and delivery.
WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization develops evidence-based immunization policy recommendations. Its Emergency Use Listing (EUL) / prequalification programmes ensure harmonized review and authorization across member states.
WHO provides global coordination and member state support on vaccine safety monitoring. It developed the target product profiles for COVID-19 vaccines and provides R&D technical coordination.
Along with COVAX partners, WHO has developed a no-fault compensation scheme as part of the time-limited indemnification and liability commitments.
WHO also led, together with UNICEF, the Country Readiness and Delivery workstream, which provided support to countries as they prepared to receive and administer vaccines.
Recognizing the urgency of turning vaccine doses into vaccinated, protected communities, WHO, UNICEF and Gavi, the Vaccine Alliance launched the COVID-19 Vaccine Delivery Partnership (CoVDP). The CoVDP builds on existing resources to support the AMC 92 and focuses foremost on the 34 countries that were at or below 10% coverage in January 2022. Working closely with countries to understand bottlenecks to vaccination, the CoVDP offers access to urgent operational funding, technical assistance and political engagement to rapidly scale up vaccination and monitor progress towards targets.
Safety of COVID-19 Vaccines
This article is part of a series of explainers on vaccine development and distribution. Learn more about vaccines – from how they work and how they’re made to ensuring safety and equitable access – in WHO’s Vaccines Explained series.
Countries around the world are rolling out COVID-19 vaccines, and a key topic of interest is their safety. Vaccine safety is one of WHO’s highest priorities, and we’re working closely with national authorities to develop and implement standards to ensure that COVID-19 vaccines are safe and effective.
Ensuring safety
Billions of people have been safely vaccinated against COVID-19. All of the approved COVID-19 vaccines have been carefully tested and continue to be monitored.
Like all vaccines, COVID-19 vaccines go through a rigorous, multi-stage testing process, including large clinical trials that involve tens of thousands of people. These trials are specifically designed to identify any safety concerns.
An external panel of experts convened by WHO analyses the results from clinical trials and recommends whether and how the vaccines should be used. Officials in individual countries decide whether to approve the vaccines for national use and develop policies for how to use the vaccines based on WHO recommendations.
After a COVID-19 vaccine is introduced, WHO supports work with vaccine manufacturers, health officials in each country and other partners to monitor for any safety concerns on an ongoing basis.
New vaccine technology
Some COVID-19 vaccines have been developed with an approach that uses messenger RNA (mRNA). The mRNA vaccine technology has been studied for over a decade, including in the development of vaccines for Zika, rabies and influenza.
These mRNA vaccines have been rigorously assessed for safety, and clinical trials have shown that they provide a long-lasting immune response. mRNA vaccines are not live virus vaccines and do not interfere with human DNA. For more information on mRNA vaccines, see WHO’s explainer on the different types of COVID-19 vaccines.
Safety of COVID-19 vaccines for different groups
COVID-19 vaccines have been tested in large, randomized controlled trials that include people of a broad age range, all sexes, different ethnicities, and those with known medical conditions. The vaccines have shown a high level of efficacy across all populations. Vaccines have been found to be safe and effective in people with various underlying medical conditions that are associated with increased risk of severe disease. These include high blood pressure; diabetes; asthma; pulmonary, liver or kidney disease; and chronic infections that are stable and controlled.
Those who should consult with a doctor before vaccination include people with a compromised immune system, older people with severe frailty, people with a history of severe allergic reaction to vaccines, people living with HIV, and those who are pregnant or breastfeeding. For more information about vaccine safety for different groups, please see our Q&A on COVID-19 vaccine safety.
Pregnancy
You can get vaccinated whilst you are pregnant. During pregnancy, you are at higher risk of serious illness caused by COVID-19. You are also at higher risk of delivering your baby prematurely if you contract COVID-19. While there is less data available on vaccination of pregnant people, evidence on the safety of COVID-19 vaccines during pregnancy has been growing, and no safety concerns have been identified. Especially in countries with high transmission, or if you have an occupation where you are at more risk of being exposed to COVID-19, the benefits of getting the vaccine outweigh potential risks. There is no risk of getting COVID-19 from the vaccine. Talk to your healthcare provider to make an informed decision about vaccination.
If you are breastfeeding, you should get vaccinated against COVID-19 as soon as it is your turn. None of the current COVID-19 vaccines have live virus in them. This means there is no risk of you transmitting COVID-19 to your baby through your breastmilk from the vaccine. In fact, the antibodies you get after vaccination may go through your breast milk and help to protect your baby.
Safety of COVID-19 vaccines for children
The Pfizer vaccine is safe for use in children aged 5 years and above. For children in this age group, WHO recommends a reduced dosage of 10 µg (0.2 ml). Both Pfizer and Moderna are safe for use in children aged 12 and above using a dose of 0.3 ml and 0.5 ml respectively. However, while the availability of COVID-19 vaccines is limited, WHO recommends that countries should vaccinate children only when high vaccine coverage with two doses has been achieved in higher priority-use groups, as identified in the WHO Prioritization Roadmap. However, children with existing health conditions should be prioritised for vaccination at the same time as other high risk groups.
Vaccine trials to determine whether other COVID-19 vaccines are safe for use in children are ongoing, and WHO recommendations will be updated when the evidence supports a change in the policy.
Practicing the protective behaviours is still the best way to keep everyone, including children, safe from COVID-19, whether or not you have been vaccinated. Keep a safe distance from others, avoid crowds, wear a well-fitting mask covering your mouth and nose, keep indoor spaces well ventilated, clean hands regularly and cover coughs and sneezes, as well as getting vaccinated as soon as it’s your turn.
This page was updated on 21 January 2022 to reflect updates in the latest guidance relating to the vaccination of children.
The different types of COVID-19 vaccines
This article is part of a series of explainers on vaccine development and distribution. Learn more about vaccines – from how they work and how they’re made to ensuring safety and equitable access – in WHO’s Vaccines Explained series.
As of December 2020, there are over 200 vaccine candidates for COVID-19 being developed. Of these, at least 52 candidate vaccines are in human trials. There are several others currently in phase I/II, which will enter phase III in the coming months (for more information on the clinical trial phases, see part three of our Vaccine Explained series).
Why are there so many vaccines in development?
Typically, many vaccine candidates will be evaluated before any are found to be both safe and effective. For example, of all the vaccines that are studied in the lab and laboratory animals, roughly 7 out of every 100 will be considered good enough to move into clinical trials in humans. Of the vaccines that do make it to clinical trials, just one in five is successful. Having lots of different vaccines in development increases the chances that there will be one or more successful vaccines that will be shown to be safe and efficacious for the intended prioritized populations.
The different types of vaccines
There are three main approaches to designing a vaccine. Their differences lie in whether they use a whole virus or bacterium; just the parts of the germ that triggers the immune system; or just the genetic material that provides the instructions for making specific proteins and not the whole virus.
The whole-microbe approach
Inactivated vaccine
The first way to make a vaccine is to take the disease-carrying virus or bacterium, or one very similar to it, and inactivate or kill it using chemicals, heat or radiation. This approach uses technology that’s been proven to work in people – this is the way the flu and polio vaccines are made – and vaccines can be manufactured on a reasonable scale.
However, it requires special laboratory facilities to grow the virus or bacterium safely, can have a relatively long production time, and will likely require two or three doses to be administered.
Live-attenuated vaccine
A live-attenuated vaccine uses a living but weakened version of the virus or one that’s very similar. The measles, mumps and rubella (MMR) vaccine and the chickenpox and shingles vaccine are examples of this type of vaccine. This approach uses similar technology to the inactivated vaccine and can be manufactured at scale. However, vaccines like this may not be suitable for people with compromised immune systems.
Viral vector vaccine
This type of vaccine uses a safe virus to deliver specific sub-parts – called proteins – of the germ of interest so that it can trigger an immune response without causing disease. To do this, the instructions for making particular parts of the pathogen of interest are inserted into a safe virus. The safe virus then serves as a platform or vector to deliver the protein into the body. The protein triggers the immune response. The Ebola vaccine is a viral vector vaccine and this type can be developed rapidly.
The subunit approach
A subunit vaccine is one that only uses the very specific parts (the subunits) of a virus or bacterium that the immune system needs to recognize. It doesn’t contain the whole microbe or use a safe virus as a vector. The subunits may be proteins or sugars. Most of the vaccines on the childhood schedule are subunit vaccines, protecting people from diseases such as whooping cough, tetanus, diphtheria and meningococcal meningitis.
The genetic approach (nucleic acid vaccine)
Unlike vaccine approaches that use either a weakened or dead whole microbe or parts of one, a nucleic acid vaccine just uses a section of genetic material that provides the instructions for specific proteins, not the whole microbe. DNA and RNA are the instructions our cells use to make proteins. In our cells, DNA is first turned into messenger RNA, which is then used as the blueprint to make specific proteins.
A nucleic acid vaccine delivers a specific set of instructions to our cells, either as DNA or mRNA, for them to make the specific protein that we want our immune system to recognize and respond to.
The nucleic acid approach is a new way of developing vaccines. Before the COVID-19 pandemic, none had yet been through the full approvals process for use in humans, though some DNA vaccines, including for particular cancers, were undergoing human trials. Because of the pandemic, research in this area has progressed very fast and some mRNA vaccines for COVID-19 are getting emergency use authorization, which means they can now be given to people beyond using them only in clinical trials.
The Janssen Ad26.COV2.S COVID-19 vaccine: What you need to know
Updated 6 June 2022, pursuant to updated interim recommendations
The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has issued interim recommendations for the use of the Janssen Ad26.COV2.S COVID-19 vaccine against COVID-19.
Here is what you need to know.
This article provides a summary of the interim recommendations; the interim recommendations and the background document are also available.
Who can take the vaccine?
The Janssen vaccine can be offered to people who have had COVID-19 in the past. But individuals may wish to choose to delay vaccination for 3 months following the infection.
Can immunocompromised persons take the vaccine?
Persons with immunocompromising conditions are at higher risk of severe COVID-19 and should be vaccinated. The WHO’s Interim recommendations for an extended primary series with an additional vaccine dose for COVID-19 vaccination in immunocompromised persons can be viewed here.
WHO recommends a second dose for all people with immunocompromising conditions aged 18 years and older. Available evidence suggests that this dose should be given 1–3 months after the first dose in order to increase protection as quickly as possible.
The most appropriate timing for a third dose may vary depending on the epidemiological setting and the extent and timing of immune suppressive therapy, and should be discussed with a Doctor. There are no data available to determine the need and timing of additional doses. As data become available, these recommendations will be updated.
Should pregnant women be vaccinated?
The Janssen vaccine is a nonreplicating vaccine. No safety issues have been identified following vaccination of more than 1,600 pregnant women using this vaccine platform for vaccines against other pathogens, such as the Ebola virus. Animal developmental and reproductive toxicity studies show no harm to the development of the foetus.
WHO has identified pregnant women as a priority-use group for COVID-19 vaccination, given their increased risk of severe outcomes. WHO recommends the use of the Janssen vaccine in pregnancy when the benefits of vaccination to the pregnant person outweigh the potential risks. This assessment should be made with the appropriate information on risks and benefits. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
Who is the vaccine not recommended for?
Individuals with a history of anaphylaxis to any component of the vaccine should not take it.
People who have had Thrombosis with thrombocytopenia (TTS) following the first dose of this vaccine should not receive a second dose of the same vaccine.
Anyone with a body temperature over 38.5ºC should postpone vaccination until they no longer have a fever.
This vaccine is not recommended for persons younger than 18 years of age pending the results of further studies in that age group.
What’s the recommended dosage?
A single dose regimen, in keeping with the EUL recommendations for this vaccine, remains an acceptable option for countries, especially when faced with supply constraints and difficulties to reach remote populations.
However, given the evidence demonstrating improved protection with a second dose, WHO recommends that all efforts should be taken to provide two doses, in particularly to the highest and high priority-use. The administration of the second dose will result in increased protection against symptomatic infection, and against severe disease.
What intervals should there be between doses?
Is it safe?
SAGE has thoroughly assessed the data on quality, safety and efficacy of the vaccine and has recommended its use for people aged 18 and above.
This vaccine has also undergone review by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) and found to be safe for use. A rare serious adverse event is the “thrombosis with thrombocytopenia syndrome” and “Guillain-Barre Syndrome”.
How efficacious is the vaccine?
Studies show that a second dose 2 months after the initial dose substantially increases efficacy, especially against symptomatic infections, including when caused by SARS-CoV-2 variants of concern. In the US, the vaccine efficacy of 2 doses, 2 months apart, was 94%. In comparison, the single dose vaccine efficacy in the USA was 72%.
Furthermore, in the single dose trial the efficacy against symptomatic disease two months after vaccination had fallen to about 50%.
Ad26.COV2.S has an acceptable reactogenicity profile after both the first dose and second dose, with the reactogenicity post-second dose being similar or milder than post-dose 1.
Does it work against new variants of SARS-CoV-2 virus?
SAGE has reviewed all available data on the performance of the vaccine in the settings of the variants of concern. In clinical trials this vaccine has been tested against a variety of SARS-CoV-2 virus variants, including B1.351 (first identified in South Africa) and P.2 (first identified in Brazil), and found to be efficacious. There are no data yet for the performance of this vaccine against the Omicron variant.
SAGE currently recommends using this vaccine, according to the WHO Prioritization Roadmap, even if variants of concern are present in a country. As new data becomes available, WHO will update recommendations accordingly.
Interchangeability between vaccine products and platforms
Evolving evidence suggests that heterologous COVID-19 vaccine schedules (using WHO EUL vaccine products from different platforms) may be more immunogenic and effective than homologous schedules, depending on the specific platforms and order of the products used.
In particular, data shows that individuals who have received one dose of the Janssen vaccine followed by a second dose of mRNA vaccine have higher neutralising antibody concentrations than individuals who received two doses of the Janssen vaccine.
Studies also show that the Janssen vaccine is as effective in boosting antibodies as a homologous third dose of mRNA vaccine when given six months after a primary two-dose series of mRNA vaccine.
Co-administration with inactivated influenza vaccines
COVID-19 vaccines may be given concomitantly, or any time before or after, other adult vaccines including inactivated influenza vaccines. Different arms for injection should be used when both vaccines are delivered during the same visit. Continued pharmacovigilance monitoring is recommended.
Does it prevent infection and transmission?
There is currently no substantive data available related to the impact of Ad26.COV2.S on transmission of virus that causes COVID-19 disease.
In the meantime, we must maintain and strengthen public health measures that work: masking, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds and ensuring good ventilation.
Adverse Events
Update: As of 27 April 2022, more than 50 million doses of Ad26.COV2.S have been administered worldwide (the majority of doses in the USA, Europe, South Africa and Brazil).
More information is available in the interim recommendations available here and includes the most recent data on any safety concerns, all of which are classified as very rare under the classification set by the Council for International Organizations of Medical Sciences.
This webpage was updated on 6 June 2022 to include the latest data and to ensure consistency of information and formatting.
The Sinovac-CoronaVac COVID-19 vaccine: What you need to know
Updated on 10 June 2022 pursuant to revised interim recommendations.
The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has issued updated interim policy recommendations for the use of the Sinovac-CoronaVac vaccine against COVID-19. This article provides a summary of those interim recommendations; you may access the full guidance document here.
Here is what you need to know.
Who can be vaccinated?
The vaccine is safe and effective for all individuals aged 18 and above. In line with the WHO Prioritization Roadmap and the WHO Values Framework, older adults, health workers and immunocompromised persons should be prioritised.
The Sinovac vaccine can be offered to people who have had COVID-19 in the past. But individuals may choose to delay vaccination for 3 months following the infection.
Should pregnant and breastfeeding women be vaccinated?
The available data on the Sinovac-CoronaVac (COVID-19) vaccine in pregnant women are insufficient to assess either vaccine efficacy or possible vaccine-associated risks in pregnancy. However, this vaccine is an inactivated vaccine with an adjuvant that is commonly used in many other vaccines with a well-documented safety profile, such as Hepatitis B and Tetanus vaccines, including in pregnant women. The effectiveness of the Sinovac-CoronaVac (COVID-19) vaccine in pregnant women is therefore expected to be comparable to that observed in non-pregnant women of similar age. Further studies are expected to evaluate safety and immunogenicity in pregnant women.
In the interim, WHO recommends the use of the Sinovac-CoronaVac (COVID-19) vaccine in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks. To help pregnant women make this assessment, they should be provided with information about the risks of COVID-19 in pregnancy; the likely benefits of vaccination in the local epidemiological context; and the current limitations of safety data in pregnant women. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or considering terminating pregnancy because of vaccination.
Vaccine effectiveness is expected to be similar in lactating women as in other adults. WHO recommends the use of the COVID-19 vaccine Sinovac-CoronaVac in lactating women as in other adults. WHO does not recommend discontinuing breastfeeding after vaccination.
Who is the vaccine not recommended for?
The vaccine is not recommended for persons younger than 18 years of age, pending the results of further studied in that age group.
Individuals with a history of anaphylaxis to any component of the vaccine should not take it.
Persons with acute PCR-confirmed COVID-19 should not be vaccinated until after they have recovered from acute illness and the criteria for ending isolation have been met.
Anyone with a body temperature over 38.5°C should postpone vaccination until they no longer have a fever.
Is it safe?
SAGE has thoroughly assessed the data on quality, safety and efficacy of the vaccine and has recommended its use for people aged 18 and above.
Safety data is currently limited for persons above 60 years of age (due to the small number of participants in clinical trials).
While no differences in safety profile of the vaccine in older adults compared to younger age groups can be anticipated, countries considering using this vaccine in persons older than 60 years should maintain active safety monitoring.
As part of the EUL process, Sinovac has committed to continuing submit data on safety, efficacy and quality in ongoing vaccine trials and rollout in populations, including in older adults.
How efficacious is the vaccine?
A large phase 3 trial in Brazil showed that two doses, administered at an interval of 14 days, had an efficacy of 51% against symptomatic SARS-CoV-2 infection, 100% against severe COVID-19, and 100% against hospitalization starting 14 days after receiving the second dose.
What is the recommended dosage?
SAGE recommends the use of Sinovac-CoronaVac vaccine as 2 doses (0.5 ml) given intramuscularly.
SAGE recommends that a third, additional dose of the Sinovac vaccine be offered to persons aged 60 and above as part of an extension of the primary series. Current data does not indicate the need for an additional dose in persons under 60 years of age.
SAGE recommends that severe and moderately immunocompromised persons should be offered an additional dose of vaccine. This is due to the fact that this group is less likely to respond adequately to vaccination following a standard primary vaccination series and are at higher risk of severe COVID-19 disease.
WHO recommends an interval of 2–4 weeks between the first and second dose of the primary series. If the second dose is administered less than 2 weeks after the first, the dose does not need to be repeated. If administration of the second dose is delayed beyond 4 weeks, it should be given at the earliest possible opportunity. When administering an additional dose to over 60s, SAGE recommends countries should initially aim at maximizing 2-dose coverage in that population, and thereafter administer the third dose, starting with the oldest age groups.
Is a booster dose recommended for this vaccine?
A booster dose may be considered 4 – 6 months after completion of the primary vaccination series, starting with the higher priority-use groups, in accordance with the WHO Prioritization Roadmap.
The benefits of booster vaccination are recognized following increasing evidence of waning vaccine effectiveness against mild and asymptomatic SARS-CoV-2 infection over time.
Either heterologous (a different vaccine product to Sinovac) or homologous (a booster dose of Sinovac) doses can be used. Studies in Chile and Brazil found that heterologous boosting resulted in superiormore robust immune responses than homologous boosting.
Can this vaccine be ‘mixed and matched’ with other vaccines?
SAGE accepts two heterologous doses of WHO EUL COVID-19 vaccines as a complete primary series.
To ensure equivalent or favourable immunogenicity or vaccine effectiveness either of the WHO EUL COVID-19 mRNA vaccines (Pfizer or Moderna) or the WHO EUL COVID-19 vectored vaccines (AstraZeneca Vaxzevria/COVISHIELD or Janssen) can be used as a second dose following a first dose with the Sinovac vaccine dependant on product availability.
Does it prevent infection and transmission?
There is currently no substantive data available related to the impact of COVID-19 vaccine Sinovac-CoronaVac on transmission of SARS-CoV-2, the virus that causes COVID-19 disease.
In the meantime, WHO reminds of the need to stay the course and continue practicing public health and social measures that should be used as a comprehensive approach to prevent infection and transmission. These measures include wearing a mask, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds and ensuring adequate ventilation according to local national advice.
Does it work against new variants of SARS-CoV-2 virus?
In an observational study, the estimated effectiveness of Sinovac-CoronaVac in health workers in Manaus, Brazil, where P.1 accounted for 75% of SARS-CoV-2 samples was 49.6% against symptomatic infection (4). Effectiveness has also been shown in an observational study in Sao Paulo in the presence of P1 circulation (83% of samples).
There are still insufficient data for Omicron.
SAGE currently recommends using this vaccine, according to the WHO Prioritization Roadmap.
How does this vaccine compare to other vaccines already in use?
We cannot compare the vaccines head-to-head due to the different approaches taken in designing the respective studies, but overall, all of the vaccines that have achieved WHO Emergency Use Listing are highly effective in preventing severe disease and hospitalization due to COVID-19.
This webpage was updated on 10 June 2022 to ensure consistency of formatting.
Coronavirus disease (COVID-19): Vaccines safety
This page answers the most frequently asked questions about COVID-19 vaccine safety. If the information you are looking for is not here, check out our related links on the right-hand side of the page.
There are strict precautions in place to help ensure the safety of all COVID-19 vaccines. Before receiving validation from WHO and national regulatory agencies for emergency use, COVID-19 vaccines must undergo rigorous testing in clinical trials to prove that they meet internationally agreed benchmarks for safety and efficacy.
Unprecedented scientific collaborations have allowed COVID-19 vaccine research, development, and authorizations to be completed in record time – to meet the urgent need for these vaccines while maintaining high safety standards. As with all vaccines, WHO and regulatory authorities will continuously monitor the use of COVID-19 vaccines to identify and respond to any safety issues that might arise. Through that process, we ascertain that they remain safe for use around the world.
The vaccines must be proven safe and effective in large Phase III clinical trials. Some COVID-19 vaccine candidates have already completed their Phase III trials and are being used globally, and many other vaccine candidates are being developed and are still in the trial phase.
Independent reviews of the efficacy and safety evidence are required by WHO for each vaccine candidate, including regulatory review and approval in the country where the vaccine is manufactured, before WHO considers it for emergency use listing.
An external panel of experts convened by WHO (the Strategic Advisory Group of Experts on Immunization (SAGE), analyses the results from clinical trials, along with evidence on the disease, age groups affected, risk factors for disease, programmatic use and other information. SAGE then recommends whether and how the vaccines should be used. In addition to reviewing data for regulatory purposes, the evidence must also be reviewed for the purpose of policy recommendations on how the vaccines should be used.
The WHO’s Global Advisory Committee on Vaccine Safety (GACVS) monitors how approved vaccines behave in the real world and to identify any signals of adverse events following immunization. GACVS is an independent group of experts providing authoritative, scientific advice to WHO on vaccine safety issues of global or regional concern.
Vaccine safety monitoring is critical at national, regional, and global levels. After any vaccine is introduced, WHO works with vaccine manufacturers, health officials, national advisory committees and other partners to monitor for any safety concerns on an ongoing basis. Specific safety concerns that arise are then evaluated by WHO and an independent group of experts (the Global Advisory Committee on Vaccine Safety, or GACVS) in conjunction with the relevant national authorities.
As is standard practice in all national immunization programmes, WHO is supporting the implementation of safety monitoring systems for COVID-19 vaccines in every country.
Suspected safety events officially reported to WHO go through a series of rapid verification steps involving the Global Advisory Committee on Vaccine Safety (GACVS). WHO then shares the results of these evaluations on its website and publishes the results of any assessments.
WHO also coordinates with local, regional, and national health officials to investigate vaccine safety concerns and advise on next steps.
Additional vaccine safety information is also made available through the Vaccine Safety Net, a global network of websites providing reliable information on vaccine safety that have been verified by WHO.
In rare situations where a serious adverse reaction is suspected to be related to the vaccine itself, the vaccine may be temporarily suspended from use while the situation is assessed. Investigations will take place to determine what exactly caused the event, and corrective measures will be put in place. WHO works closely with vaccine manufacturers, health officials, researchers, and other partners to monitor any safety concerns and potential side effects.
Vaccine recalls or withdrawals due to safety issues are rare. Recalls are generally associated with problems identified during the monitoring of batches of vaccines through quality control systems, stability studies and reports from the field, including cold chain issues where some vaccines have not been stored at the right conditions and so are no longer safe or effective. In this case, people who have received a vaccine from that batch may need to be vaccinated again to ensure they are protected. This is why vaccines are so closely monitored – to ensure that any issues with their production, storage or use can be rapidly identified and resolved.
Like with any vaccine, some people will experience mild to moderate side effects after being vaccinated against COVID-19. This is a normal sign that the body is developing protection. Side effects to COVID-19 vaccines include a fever, tiredness, headache, muscle ache, chills, diarrhoea and pain or redness at the injection site. Not everyone will experience side effects. Most side effects go away within a few days on their own. You can manage any side effects with rest, plenty of non-alcoholic liquids and taking medication to manage pain and fever, if needed.
If you are worried that the side effects that you are experiencing are unusual, if the pain in the arm where you got the injection gets worse after 24 hours or your side effects don’t go away in a few days, contact your healthcare provider for advice.
More serious or long-lasting side effects to COVID-19 vaccines are possible but extremely rare. If you experience difficulty breathing, chest pain, confusion, loss of speech or mobility after your vaccine, contact your healthcare provider immediately. Vaccines are continually monitored for as long as they are in use to detect and respond to rare adverse events.
The vaccine stimulates your immune system to protect you from the virus. This process can sometimes cause side effects like fever, chills or headache, but not everyone will experiences any side effect. The presence or magnitude of the reaction you may have vaccination does not predict or reflect your immune response to the vaccine.
You do not have to have side effects in order to be protected.
If you are worried about your side effects, contact your healthcare provider and let them know about your recent vaccination.
In very rare cases, some people may experience an allergic reaction after being vaccinated against COVID-19. A severe allergic reaction – such as anaphylaxis – is a very rare side effect of any vaccine.
If you have a history of allergic reactions, talk to your healthcare provider before you get vaccinated. They will be able to give you advice. In some cases, precautions will need to be taken for people who have known allergies to previous doses of the vaccine or known components of the vaccine.
Healthcare workers administering COVID-19 vaccines should be trained to recognise and treat serious allergic reactions. This is why people being vaccinated against COVID-19 will be asked to stay at the vaccination site for a period of time following their injection, to ensure that anyone experiencing an allergic reaction can receive prompt treatment.
Reports of adverse events following COVID-19 vaccination (including allergic reactions) are closely monitored by national authorities and international bodies, including WHO for the early detection of serious side effects.
As with any vaccine, it is essential to closely monitor the safety and effectiveness of COVID-19 vaccines that are used in immunization programmes. If a serious health problem is reported following vaccination, a thorough investigation should take place by the public health programme in the country.
It is rare to find that health problems occurring following receipt of a vaccine are actually caused by the vaccine itself. Health problems following vaccination are most often found to be coincidental and entirely unrelated to vaccination. Sometimes they are related to how the vaccine has been stored, transported, or administered. Errors related to the delivery of the vaccine can be prevented by better training health workers and strengthening supply chains.
The results of the investigation will then inform next steps. The safety of COVID-19 vaccines is the top priority of the World Health Organization.
It is safe for you to receive two different COVID-19 vaccines for your first and second dose. This is sometimes called mixing and matching vaccines, or a heterologous vaccine schedule. WHO considers two doses of any WHO EUL COVID-19 vaccines to be a complete primary series. See the full list of COVID-19 vaccines with WHO EUL here.
By mixing and matching vaccines, countries are able to maximise vaccine impact in the event of constrained or limited supply.
People over 60 who have received two doses of Sinovac and Sinopharm can also be given a third dose to help boost their immunity, once a high level of coverage of the priority groups has been achieved. SAGE has stated that Pfizer or AstraZeneca can be used for the third dose if the original vaccine is not available.
Further trials are underway to understand more about mixed doses, which will inform any future changes to WHO’s recommendations.
Women can receive a vaccine at any point in their menstrual cycle.
The COVID-19 mRNA vaccine technology has been rigorously assessed for safety, and clinical trials have shown that mRNA vaccines produce an immune response that has high efficacy against disease. mRNA vaccine technology has been studied for several decades, including in the contexts of Zika, rabies, and influenza vaccines. mRNA vaccines are not live virus vaccines and do not interfere with human DNA.
Globally, mRNA vaccines such as Pfizer and Moderna have been used to protect millions of people against COVID-19. A significant amount of data is available from both clinical trials and country surveillance programmes on their efficacy and safety. Some mild side effects are expected after vaccination; these are a normal sign that the body is developing protection.
There have been reports of very rare cases of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the membrane surrounding the heart) following the second dose of mRNA COVID-19 vaccines. Myocarditis and pericarditis can be caused by many factors, including infections, viruses, medicines and environmental factors. The currently available data suggests that there is also a potential relationship between these symptoms and mRNA vaccines. Research is underway to understand more.
Cases have been mostly reported in younger men aged 12 – 29 (40.6 cases of myocarditis per million second doses) compared to females of the same age group (4.2 cases per million second doses)[1].
The symptoms of myocarditis and pericarditis are generally mild. Fast treatment with medication and rest can help to avoid long term heart damage and death. If you experience new and persisting chest pain, shortness of breath or have a racing or pounding heartbeat within a few days of vaccination, contact your doctor immediately. The benefits of these vaccines greatly outweigh the risk of myocarditis and pericarditis by preventing deaths and hospitalisations due to COVID-19.
For more information, please read the updated guidance from the COVID-19 subcommittee of the WHO Global Advisory Committee on Vaccine Safety (GACVS).
Globally, COVID-19 vaccines such as AstraZeneca and Johnson &Johnson/Janssen have been used to protect millions of people. Data is available from both clinical trials and preliminary data from country surveillance programmes on their efficacy and safety. Some mild to moderate side effects such as fever, muscle and head aches, soreness around the injection site and tiredness are expected to affect some people after vaccination. These are a normal indications that the body is developing protection.
There have been reports of very rare but serious cases of blood clots accompanied by low platelet counts (known as thrombosis with thrombocytopenia syndrome (TTS)) occurring 3 to 30 days after vaccination with COVID-19 non-replicant adenovirus vector-based vaccines (such as the AstraZeneca and Janssen vaccines). Read more about the different types of COVID-19 vaccines.
With the Janssen vaccine, as of the 7 May 2021, the US Food and Drug Administration and the Centers for Disease Control and Prevention had reviewed 28 reports of TTS out of a total of more than eight million people vaccinated[3]. It is possible that that there a causal link between the vaccine and these symptoms, but more data is needed.
TTS is very rare; however, blood clotting is a common health problem caused by many factors. Not all clots that occur after vaccination with Astra Zeneca or the Janssen vaccine will be due to TTS. The risk of blood clots is far higher from COVID-19 itself than from either vaccine.
If you experience a new, severe, persistent headache, blurred vision, chest pain, severe abdominal pain, leg swelling or unusual skin bruising and shortness of breath between three to 30 days following vaccination, contact your doctor immediately. WHO has published interim guidance for clinical case management of TTS following vaccination.
The benefits of the COVID-19 Astra Zeneca and Janssen vaccines are far greater than the very small risk of TTS. As well as protecting you from severe disease and death due to COVID-19, being vaccinated can protect you against complications from ‘long COVID’, provide some protection for your close contacts and community by reducing transmission, and can reduce the risk of severe disease from some variant strains. WHO recommends that these vaccines continue to be used to protect priority groups.
Globally, vaccines such as AstraZeneca and Johnson &Johnson/Janssen have been used to protect millions of people against COVID-19. Data is available from both clinical trials and preliminary data from country surveillance programmes on their efficacy and safety. Some mild to moderate side effects such as fever, muscle and head aches, soreness around the injection site and tiredness are expected to affect some people after vaccination. These are a normal indications that the body is developing protection.
There have been very rare reports of cases of Guillain-Barré syndrome occurring within 42 days of vaccination with the AstraZeneca and Janssen vaccines (adenovirus vector vaccines). Guillain-Barré syndrome is a rare condition in which a person’s immune system attacks the nerves, causing muscle weakness, tingling and/or loss of sensation in the arms and/or legs. Most people affected recover fully. Although these cases happened after vaccination, it is not yet possible to tell whether they were related to or caused by the vaccines, or if they were coincidental. The benefits of vaccination against COVID-19 greatly outweigh any possible risk.
As of the 27 June, the European Medicines Agency had received reports of 227 cases of Guillain-Barré syndrome in the European Union following vaccination with AstraZeneca. Around 51.4 million doses of Vaxzevria (the brand of AstraZeneca produced in Europe) had been administered within the European Union by 20 June 2021. For the Janssen vaccine, the US Advisory Committee on Immunization Practices reported that 100 cases of Guillain-Barré syndrome had been reported through the Vaccine Adverse Events Reporting System in the United States of America (USA) as of 30 June, with approximately 12.2 million doses of the Janssen vaccine administered. Outside of the European Union and the USA, cases of Guillain-Barré syndrome have also been reported; however further investigation is needed to determine whether the rate has increased from usual levels.
Guillain-Barré syndrome has many causes, such as bacterial or viral infections, surgery or vaccine administration. It can also be caused by COVID-19. In 2011, it was estimated that the incidence of Guillain-Barré syndrome in Europe and Northern America was 0.8 to 1.9 cases out of every 100 000 people [4]. It can affect people of all ages but is more common in adults and in males. Most people recover fully even from the most severe cases of Guillain-Barré syndrome; however, it is potentially life threatening and some people affected may need intensive care.
If you experience any of the following symptoms within 42 days of vaccination, contact your healthcare provider immediately:
The benefits of the COVID-19 Janssen and AstraZeneca vaccines are far greater than the very small risk of Guillain-Barré syndrome. As well as protecting you from severe disease and death due to COVID-19, being vaccinated can protect you against complications from ‘long COVID’, provide some protection for your close contacts and community by reducing transmission, and can reduce the risk of severe disease from variant strains. COVID-19 disease can also cause Guillain-Barré syndrome. WHO recommends that these vaccines continue to be used to protect priority groups.
[1] US Vaccine Adverse Events Reporting System (VAERS) as of June 11 2021, this is in the updated guidance from GACVS
WHO releases global COVID-19 vaccination strategy update to reach unprotected
WHO published an update to the Global COVID-19 Vaccination Strategy today, in response to the spread of Omicron subvariants, advances in vaccine evidence, and lessons from the global vaccination program.
In the first year of rollouts, COVID-19 vaccines are estimated to have saved 19.8 million lives. Through unprecedently large and rapid rollouts worldwide, over 12 billion doses have been administered globally, in nearly every country in the world, resulting in countries reaching 60% of their populations on average.
Yet only 28% of older populations and 37% of health care workers in low-income countries have been vaccinated with their primary series. 27 of WHO’s Member States have not yet started a booster or additional dose program, 11 of which are low-income countries.
The strategy aims to use primary and booster doses to reduce deaths and severe disease, in order to protect health systems, societies and economies. On the way to reaching the 70% vaccination target, countries should prioritize achieving the underpinning targets of vaccinating 100% of health care workers and 100% of the most vulnerable groups, including older populations (over 60s) and those who are immunocompromised or have underlying conditions.
“Even where 70% vaccination coverage is achieved, if significant numbers of health workers, older people and other at-risk groups remain unvaccinated, deaths will continue, health systems will remain under pressure and the global recovery will be at risk,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Vaccinating all those most at risk is the single best way to save lives, protect health systems and keep societies and economies open.”
To ensure vaccines reach the highest priority groups, the strategy emphasizes the need for measuring progress in vaccinating these groups and developing targeted approaches to reach them. Approaches include using local data and engaging communities to sustain demand for vaccines, building systems for vaccinating adults, and reaching more displaced people through humanitarian response.
The strategy also has the goal of accelerating development and ensuring equitable access to improved vaccines to substantially reduce transmission as the top priority but also to achieve durable, broadly protective immunity.
Current vaccines were designed to prevent serious illness and death, which they have succeeded in doing, saving millions of lives. However, they have not substantially reduced transmission. As the virus continues to circulate widely, new and dangerous variants are emerging, including some which reduce the efficacy of vaccines. It is fundamental to continue investing in research and development to make more effective, easier to administer vaccines, such as nasal spray products.
Other vital actions to take include: equitably distributing manufacturing facilities across regions and supporting strong vaccine delivery programs. WHO will continue to collaborate with COVAX and COVID-19 Vaccine Delivery Partnership (CoVDP) partners to support countries with rollouts, such as through packaging COVID-19 vaccination with other health interventions.
Note to editors:
The Global COVID-19 Vaccination Strategy in a Changing World: July 2022 update can be read in its entirety here.
WHO validates 11th vaccine for COVID-19
Today, the World Health Organization (WHO) issued an emergency use listing (EUL) for CONVIDECIA, a vaccine manufactured by CanSino Biologics, China, adding to a growing portfolio of vaccines validated by WHO for the prevention of COVID-19 caused by SARS-CoV-2.
WHO’s EUL procedure assesses the quality, safety and efficacy of COVID-19 vaccines as a prerequisite for COVAX vaccine supply. It also allows countries to expedite their own regulatory approval to import and administer COVID-19 vaccines.
CONVIDECIA was assessed under the WHO EUL procedure based on the review of data on quality, safety, efficacy, a risk management plan, programmatic suitability and a manufacturing site inspection conducted by WHO. The Technical Advisory Group for Emergency Use Listing, convened by WHO and made up of regulatory experts from around the world, has determined that the vaccine meets WHO standards for protection against COVID-19 and that the benefits of the vaccine far outweigh risks.
CONVIDECIA is based on a modified human adenovirus that expresses the spike S protein of SARS-CoV-2. It is administered as a single dose.
CONVIDECIA was also reviewed earlier this month by WHO’s Strategic Advisory Group of Experts on Immunization (SAGE), which formulates vaccine specific policies and recommendations for vaccines’ use in populations (i.e. recommended age groups, intervals between shots, specific groups such as pregnant and lactating women).
The SAGE recommends use of the vaccine as a single (0.5ml) dose, in all age groups 18 and above.
CONVIDECIA was found to have 58% efficacy against symptomatic disease and 92% against severe COVID-19.
WHO emergency use listing
The emergency use listing (EUL) procedure assesses the suitability of novel health products during public health emergencies. The objective is to make medicines, vaccines and diagnostics available as rapidly as possible to address the emergency while adhering to stringent criteria of safety, efficacy and quality. The assessment weighs the threat posed by the emergency as well as the benefit that would accrue from the use of the product against any potential risks.
The EUL pathway involves a rigorous assessment of late phase II and phase III clinical trial data as well as substantial additional data on safety, efficacy, quality and a risk management plan. These data are reviewed by independent experts and WHO teams who consider the current body of evidence on the vaccine under consideration, the plans for monitoring its use, and plans for further studies.
As part of the EUL process, the company producing the vaccine must commit to continue to generate data to enable full licensure and WHO prequalification of the vaccine. The WHO prequalification process will assess additional clinical data generated from vaccine trials and deployment on a rolling basis to ensure the vaccine consistently meets the necessary standards of quality, safety and efficacy for broader availability.
SAGE
SAGE is the principal advisory group to WHO for vaccines and immunization. It is charged with advising WHO on overall global policies and strategies, ranging from vaccines and immunization technology, research and development, to delivery of immunization and its linkages with other health interventions. SAGE is concerned not just with childhood vaccines and immunization, but all vaccine-preventable diseases.
SAGE assesses evidence on safety, efficacy, effectiveness, impact and programmatic suitability, considering both individual and public health impact. SAGE Interim recommendations for EUL products provide guidance for national vaccination policy makers. These recommendations are updated as additional evidence becomes available and as there are changes to the epidemiology of disease and the availability of additional vaccines and other disease control interventions.
CORRIGENDUM. Please note this webpage was updated on 23 May 2022 to give the efficacy rate after 28 days.
World health organization vaccines covid
It’s only impossible until it’s done — Nelson Mandela
In 2021, WHO set the target for 70% global vaccination coverage by mid-2022. As of June 2022 only 58 of WHO’s 194 Member States had reached the 70% target and only in low-income countries, just 37% of healthcare workers had received a complete course of primary vaccination.
The conditions to allow for all countries to achieve the global targets, meaning supply, technical support, and financial supply, are now in place. Thanks to coordination between global, regional, and bilateral vaccine suppliers and manufacturers, low and lower-middle countries can now better match the supply of vaccines arriving in country with their own country specific demand for doses.
For the first time since the pandemic began, the global supply of vaccines is not currently a binding constraint.
And while trade bottlenecks are being tackled and export restrictions are being rolled back, exports of some vaccination-related products remain restricted, indicating persistent global shortages.2 This means the overarching challenge is now vaccine delivery – getting shots into arms.
A continued, concerted and country-led push to deliver against nationally defined vaccination strategies can act in support of global targets.
The greatest benefits within that approach will come from prioritizing full vaccination and boosters for high-risk populations – older adults, healthcare workers, and persons with co-morbidities including immunocompromised persons.
The solution
Strong leadership engagement and commitment to detailed and costed vaccination plans will be essential. Momentum to vaccinate high-priority groups, like healthcare workers, over 60s and people who are immunocompromised, must be maintained.
National healthcare system capacity will need to be strengthened. Increasingly COVID-19 vaccination services will need to be integrated with other immunization services and alongside other health and social interventions for maximum impact and to build long-term capacity.
As people’s risk perception of the virus wanes, careful risk communication and community engagement plans need to be adapted to enhance demand for vaccination, and domestic and international funding needs to be coordinated, available and swift to deliver against clear country plans.
The COVID-19 Vaccine Delivery Partnership, a collective international effort with ‘One Country Team’, ‘One Plan’, and ‘One Budget’ was launched by WHO, UNICEF, and Gavi with international partners including the World Bank to intensify country readiness and intensify delivery support. It focuses on 34 low coverage countries, with the government at the center, to accelerate COVID-19 vaccination.
Despite incremental success since its launch in January 2022, low and lower-middle income countries are facing difficulties to get a step change in vaccination rates.
This represents a serious threat to the fragile economic recovery, including due to the risk of new variants creating large waves of serious disease and death in populations with low vaccination coverage. It also means accelerating the delivery of other COVID-19 tools and treatments is a crucial priority to help the world build up multiple layers of protection against the virus. Concerted and urgent action from countries, international partners and agencies, along with G20 Finance Ministers is required to increase vaccination levels and expedite access.
WHO lists additional COVID-19 vaccine for emergency use and issues interim policy recommendations
WHO today listed the Sinopharm COVID-19 vaccine for emergency use, giving the green light for this vaccine to be rolled out globally. The Sinopharm vaccine is produced by Beijing Bio-Institute of Biological Products Co Ltd, subsidiary of China National Biotec Group (CNBG).
“The addition of this vaccine has the potential to rapidly accelerate COVID-19 vaccine access for countries seeking to protect health workers and populations at risk,” said Dr Mariângela Simão, WHO Assistant-Director General for Access to Health Products. “We urge the manufacturer to participate in the COVAX Facility and contribute to the goal of more equitable vaccine distribution.”
WHO’s Emergency Use Listing (EUL) is a prerequisite for COVAX Facility vaccine supply. It also allows countries to expedite their own regulatory approval to import and administer COVID-19 vaccines.
The EUL assesses the quality, safety and efficacy of COVID-19 vaccines, as well as risk management plans and programmatic suitability, such as cold chain requirements. The assessment is performed by the product evaluation group, composed by regulatory experts from around the world and a Technical Advisory Group (TAG), in charge of performing the risk-benefit assessment for an independent recommendation on whether a vaccine can be listed for emergency use and, if so, under which conditions.
In the case of the Sinopharm vaccine, the WHO assessment included on-site inspections of the production facility.
The Sinopharm product is an inactivated vaccine called SARS-CoV-2 Vaccine (Vero Cell). Its easy storage requirements make it highly suitable for low-resource settings. It is the also first vaccine that will carry a vaccine vial monitor, a small sticker on the vaccine vials that change color as the vaccine is exposed to heat, letting health workers know whether the vaccine can be safely used.
WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) has also completed its review of the vaccine. On the basis of all available evidence, WHO recommends the vaccine for adults 18 years and older, in a two-dose schedule with a spacing of three to four weeks. Vaccine efficacy for symptomatic and hospitalized disease was estimated to be 79%, all age groups combined.
Few older adults (over 60 years) were enrolled in clinical trials, so efficacy could not be estimated in this age group. Nevertheless, WHO is not recommending an upper age limit for the vaccine because preliminary data and supportive immunogenicity data suggest the vaccine is likely to have a protective effect in older persons. There is no theoretical reason to believe that the vaccine has a different safety profile in older and younger populations. WHO therefore recommends that countries using the vaccine in older age groups conduct safety and effectiveness monitoring to make the recommendation more robust.
WHO emergency use listing
The emergency use listing (EUL) procedure assesses the suitability of novel health products during public health emergencies. The objective is to make medicines, vaccines and diagnostics available as rapidly as possible to address the emergency, while adhering to stringent criteria of safety, efficacy and quality. The assessment weighs the threat posed by the emergency as well as the benefit that would accrue from the use of the product against any potential risks.
The EUL pathway involves a rigorous assessment of late phase II and phase III clinical trial data as well as substantial additional data on safety, efficacy, quality and a risk management plan. These data are reviewed by independent experts and WHO teams who consider the current body of evidence on the vaccine under consideration, the plans for monitoring its use, and plans for further studies.
As part of the EUL process, the company producing the vaccine must commit to continue to generate data to enable full licensure and WHO prequalification of the vaccine. The WHO prequalification process will assess additional clinical data generated from vaccine trials and deployment on a rolling basis to ensure the vaccine meets the necessary standards of quality, safety and efficacy for broader availability.
WHO also listed the Pfizer/BioNTech vaccine for emergency use on 31 December 2020; two AstraZeneca/Oxford COVID-19 vaccines on 15 February 2021, produced by AstraZeneca-SKBio (Republic of Korea) and the Serum Institute of India; and COVID-19 vaccine Ad26.COV2.S developed by Janssen (Johnson & Johnson) on 12 March 2021.
Listings
SAGE
SAGE is the principal advisory group to WHO for vaccines and immunization. It is charged with advising WHO on overall global policies and strategies, ranging from vaccines and technology, research and development, to delivery of immunization and its linkages with other health interventions. SAGE is concerned not just with childhood vaccines and immunization, but all vaccine-preventable diseases.
SAGE has issued recommendations on Pfizer (8 January 2021), Moderna (25 January 2021), AstraZeneca (21 April 2021), and Janssen COVID (17 March 2021) vaccines, as well as issued a framework for access and population prioritization roadmap.
SAGE and EUL are complementary but independent processes. The EUL process is centered on determining if a manufactured product is quality-assured, safe and effective. SAGE is policy oriented. Policy recommendations for a vaccine are only of value to a vaccination campaign when the product has been listed or authorized for use.
In the context of COVID-19 and due the pressing need for vaccines, the Secretariat of SAGE and the EUL team have been working in parallel to allow WHO EUL and policy recommendations, based on the available evidence, to be issued in a synchronized manner.
The Moderna COVID-19 (mRNA-1273) vaccine: what you need to know
Updated 18 August 2022, to adhere to the latest SAGE recommendations.
The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has issued updated interim recommendations for the use of the Moderna COVID-19 (mRNA-1273) vaccine against COVID-19. This article provides a summary of those interim recommendations; you may access the full guidance document here.
Here is what you need to know.
Who can be vaccinated?
The vaccine is safe and effective for all individuals aged 6 months and above. In line with the WHO Prioritization Roadmap and the WHO Values Framework, older adults, health workers and immunocompromised persons should be prioritised.
The Moderna vaccine can be offered to people who have had COVID-19 in the past. But individuals may choose to delay vaccination for 3 months following the infection.
Should pregnant and breastfeeding women be vaccinated?
Given the adverse consequences of COVID-19 during pregnancy and the increasing data supporting a favorable safety profile of mRNA-1273 in pregnancy, WHO recommends the use of mRNA-1273 in pregnant individuals. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
Vaccine effectiveness is expected to be similar in breastfeeding women as in other adults. WHO recommends the use of the vaccine in breastfeeding women as in other adults. In addition, vaccine-elicited antibodies have been found in breast milk following vaccination of breastfeeding women, suggesting possible neonatal as well as maternal protection. WHO does not recommend discontinuing breastfeeding because of vaccination.
Who should not take the vaccine?
Individuals with a history of severe allergic reaction to any component of the vaccine should not take this or any other mRNA vaccine.
Individuals who developed myocarditis or pericarditis following the first dose of mRNA-1273 vaccine should not receive additional doses of any COVID vaccine unless with the recommendation of their doctor or a healthcare professional.
Can children and adolescents take the vaccine?
This vaccine is authorized for use for those aged 6 months and above, with an adjustment in the recommended dosage in those aged 6 months – 4 years, and those aged 5-11 years.
WHO recommends that countries should consider using the vaccine in children aged 6 months to 17 years only when high vaccine coverage with 2 doses has been achieved in the high priority groups as identified in the WHO Prioritization Roadmap.
Children and adolescents aged 6 months to 17 years of age with comorbidities that put them at significantly higher risk of serious COVID-19 disease, should be offered vaccination, alongside other high-risk groups.
Studies on the safety and efficacy of the vaccine in children aged below 12 are still ongoing.
In accordance with the WHO Prioritization Roadmap, the priority remains to prevent deaths by achieving high vaccine coverage (primary series and boosters) in the highest and high priority-use groups. In general, children are at lower risk of COVID-19. That is why WHO recommends that countries prioritize vaccinating people who have higher risk first.
Is it safe?
On 30 April 2021, WHO listed the Moderna vaccine for emergency use. WHO’s Emergency Use Listing (EUL) assesses the quality, safety and efficacy of COVID-19 vaccines and is a prerequisite for COVAX Facility vaccine supply.
The Global Advisory Committee on Vaccine Safety, a group of experts that provides independent and authoritative guidance to the WHO on the topic of safe vaccine use, receives and assesses reports of suspected safety events of potentially international impact. In October 2021, the GACVS COVID-19 subcommittee concluded that the mRNA COVID-19 vaccines have clear benefits in all age groups in reducing hospitalizations and deaths due to COVID-19.
A very rare serious adverse event is myocarditis, which is mainly observed in young males aged 18-35 after the second dose. These myocarditis cases typically occurred within a few days after vaccination, are generally mild, respond to conservative treatment, and are less severe with better outcomes than classical myocarditis or COVID-19 related myocarditis.
How efficacious is the vaccine?
The Moderna vaccine after two doses and a first booster dose has been shown to have very high effectiveness against severe disease, hospitalizations and death, and modest effectiveness against symptomatic illness.
What’s the recommended dosage?
For adults aged 17 and above, SAGE recommends the use of the Moderna mRNA-1273 vaccine at a schedule of two doses (100 µg, 0.5 ml each) 8 weeks apart.
For adolescents aged 12 to 17 years, SAGE recommends 2 doses (100 µg, 0.5 ml each), given intramuscularly, 4 weeks apart.
For children aged 6 to 11 years, SAGE recommends 2 doses (50µg in 0.25 ml each), 4 weeks apart.
For children aged 6 months to 5 years, SAGE recommends 2 doses (25 µg [0.25 ml each), 4 weeks apart.
WHO recommends that the second dose should be administered 4–8 weeks after the first dose; an interval of 8 weeks between doses is preferred as this interval is associated with higher vaccine effectiveness and lower risk of myocarditis.
Compliance with the full schedule is recommended and the same product can be used for both doses.
SAGE recommends that severe and moderately immunocompromised persons should be offered an additional dose of vaccine. This is due to the fact that this group is less likely to respond adequately to vaccination following a standard primary vaccination series and are at higher risk of severe COVID-19 disease.
Is a booster dose recommended for this vaccine?
The first booster dose is recommended for the highest priority-use groups (e.g. older adults, persons with moderate to severe immunocompromising conditions, and health workers), 4-6 months after the completion of the primary series. If more than 6 months have elapsed since completion of the primary series, the booster dose should be given at the earliest opportunity.
WHO recommends countries should consider a second booster dose 4-6 months after the first booster dose for the highest priority groups.
For persons aged 12 and above, WHO recommends the dosage of the booster dose is half the dose used in the primary vaccination series (50 µg at 0.25 ml). The benefits of booster vaccination are recognized following increasing evidence of waning vaccine effectiveness against mild and asymptomatic SARS-CoV-2 infection over time.
There is currently no recommendation for either first or second booster doses in children under the age of 12, except for children with immunocompromising conditions.
Can this vaccine be ‘mixed and matched’ with other vaccines?
SAGE accepts two heterologous doses of WHO EUL COVID-19 vaccines as a complete primary series.
For countries considering heterologous schedules, (e.g. using different COVID-19 vaccine platforms), WHO has made the following recommendations:
Does it prevent infection and transmission?
There is only modest impact on preventing mild infections and transmission, particularly in the context of Omicron.
Immunity persists for several months, but the full duration is not yet known. A booster dose restores vaccine effectiveness against Omicron, in particular against severe disease.
In the meantime, we must maintain public health measures that work: masking, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds, and ensuring good ventilation.
Does it work against new variants?
The vaccine remains effective against virus variants, though for the Omicron variant, vaccine effectiveness against severe and mild disease after two doses is lower compared to Delta, and waning is more rapid. Therefore, a third dose (first booster) is recommended for all adults, and a second booster for the highest priority-use groups.
How does this vaccine compare to other COVID-19 vaccines already in use?
It is impossible to compare vaccines head-to-head due to the different approaches taken in designing the respective studies, but overall, all of the vaccines that have achieved WHO Emergency Use Listing are highly effective in preventing severe disease and hospitalization due to COVID-19.
This webpage was updated on 18 August 2022 to reflect the latest guidance.
This webpage was updated on 10 June 2022 to ensure consistency of formatting.
This webpage was updated on 23 February 2022 to update the latest guidance.
This webpage was updated on 5 January 2022 to update the latest guidance and ensure consistency of information and formatting.
This article was revised on 29 January 2021 to include a section dedicated to pregnant women, but the recommendations remain the same.
The Novavax vaccine against COVID-19: What you need to know
This webpage was updated on 13 June 2022 to ensure consistency of formatting.
The Technical Advisory Group for Emergency Use Listing listed Nuvaxovid (NVX-CoV2373) vaccine against COVID-19 and Covovax (NVX-CoV2373) vaccine against COVID-19 for emergency use on 20 December 2021 and 17 December 2021 respectively.
The Novavax vaccine will be manufactured in two different facilities. In Europe, the vaccine will be manufactured under the trade name Nuvaxovid and has been approved by the European Medicines Agency, and in India, the vaccine will be manufactured by Serum Institute of India under the trade name Covovax and has been approved by the Drugs Controller General of India.
The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has issued interim policy recommendations for the use of the Novavax (NVX-CoV2373) vaccine. This article provides a summary of those interim recommendations.
For the purposes of this article, the vaccine will be referred to as Novavax (NVX-CoV2373).
The background documents are also available here.
Who can take this vaccine?
The vaccine is safe and effective for all individuals aged 18 and above. In line with the WHO Prioritization Roadmap and the WHO Values Framework, older adults, health workers and immunocompromised persons should be prioritised.
The Novavax vaccine can be offered to people who have had COVID-19 in the past. But individuals may choose to delay vaccination for 3 months following the infection.
Should pregnant and breastfeeding women be vaccinated?
Data regarding the safety and efficacy of the use of Novavax (NVX-CoV2373) vaccine in pregnant women is not yet available. However, based on previous evidence from other protein-based vaccines during pregnancy, efficacy is expected to be comparable to non-pregnant women of a similar age.
WHO recommends the use of the COVID-19 vaccine in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks. To help pregnant women make this assessment, they should be provided with information about the risks of COVID-19 in pregnancy, the likely benefits of vaccination in the local epidemiological context, and the current limitations of safety data in pregnant women. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
WHO recommends the same use of Novavax (NVX-CoV2373) vaccine in breastfeeding and non-breastfeeding women. Data are not available on the potential benefits or possible risks of the Novavax (NVX-CoV2373) vaccine to breastfed children. However, as Novavax (NVX-CoV2373) vaccine is not a live virus vaccine, it is biologically and clinically unlikely to pose a risk to the breastfeeding child. WHO does not recommend discontinuing breastfeeding because of vaccination.
Who is the vaccine not recommended for?
The vaccine is not recommended for people younger than 18 years of age. Safety and immunogenicity data for under-18s are currently being generated but until such data are sufficiently available and can be further reviewed, vaccination of individuals in this age group is not recommended.
Individuals with a history of anaphylaxis to any component of the vaccine should not take it.
Persons with acute PCR-confirmed COVID-19 should not be vaccinated until after they have recovered from acute illness and the criteria for ending isolation have been met.
Anyone with a body temperature over 38.5°C should postpone vaccination until they no longer have a fever.
Is it safe?
SAGE has thoroughly assessed the data on the safety and efficacy of the vaccine and has recommended its use for people aged 18 and above. The WHO EUL process also evaluates the quality of manufacturing along with safety and efficacy.
Safety data is currently limited for persons above 65 years of age (due to the small number of participants of this age group in clinical trials). However, the trial data indicate that the vaccine has an acceptable safety profile for this age group and WHO recommends the vaccine for use in persons aged 65 years and over.
How efficacious is the vaccine?
The efficacy of Novavax (NVX-CoV2373) has been assessed in three Phase 2 and Phase 3 trials. Of the two Phase 3 trials, both found that the efficacy of the vaccine against mild, moderate, and severe disease is 90%.
What is the recommended dosage?
SAGE recommends the use of the Novavax (NVX-CoV2373) vaccine as 2 doses (0.5 ml) given intramuscularly. The two doses should be administered with an interval of 3-4 weeks.
SAGE recommends that severe and moderately immunocompromised persons should be offered an additional dose of vaccine. This is due to the fact that this group is less likely to respond adequately to vaccination following a standard primary vaccination series and are at higher risk of severe COVID-19 disease.
Can this vaccine be ‘mixed and matched’ with other vaccines?
SAGE accepts two heterologous doses of WHO EUL COVID-19 vaccines as a complete primary series. However, there is limited evidence available on the use of Novavax (NVX-CoV2373) in a heterologous schedule.
Does it prevent infection and transmission?
As there is not currently sufficient evidence to date to evaluate the impact of the vaccine on transmission, public health and social measures must continue, including use of face masks, physical distancing, handwashing, appropriate ventilation, and other measures as appropriate in particular settings, depending on the COVID-19 epidemiology and potential risks of emerging variants. Government advice on public health and social measures should continue to be followed by both vaccinated and unvaccinated individuals. SAGE will update this advice as information on the impact of vaccination on virus transmission and indirect protection is assessed.
Does it work against new variants of SARS-CoV-2 virus?
In a Phase 3 study conducted in the USA and Mexico during a period in which multiple variants (Alpha, Beta and Delta) were in circulation, vaccine efficacy against mild, moderate, or severe COVID-19 was 90%.
In view of these findings, WHO recommends the use of Novavax (NVX-CoV2373) vaccine according to the WHO Prioritization Roadmap, even if currently recognized Variants of Concern (VOC) are present in the country. If new VOCs emerge for which vaccine performance is compromised, these recommendations will be updated accordingly. There are insufficient data still for Omicron.
How does this vaccine compare to other COVID-19 vaccines already in use?
It is impossible to compare vaccine head-to-head due to the different approaches taken in designing the respective studies, but overall, all of the vaccines that have achieved WHO Emergency Use Listing are highly effective in preventing severe disease and hospitalization due to COVID-19.
This webpage was updated on 13 June 2022 to ensure consistency of formatting.
The Pfizer BioNTech (BNT162b2) COVID-19 vaccine: What you need to know
Updated 18 August 2022, to reflect the latest SAGE recommendations
The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has issued interim recommendations for the use of the Pfizer BioNTech (BNT162b2) vaccine against COVID-19. This article provides a summary of those interim recommendations; you may access the full guidance document here.
Here is what you need to know.
According to SAGE, the Pfizer-BioNTech COVID-19 mRNA vaccine is safe and effective.
Who can take the vaccine?
The vaccine is safe and effective for all individuals aged 6 months and above. In line with the WHO Prioritization Roadmap and the WHO Values Framework, older adults, immunocompromised persons and health workers are the highest priority-use groups. All efforts should be taken to achieve high vaccine coverage rates in the highest and high priority-use groups.
Should pregnant and breastfeeding women be vaccinated?
Given the adverse consequences of COVID-19 disease during pregnancy and the increasing data supporting a favorable safety profile of BNT162b2 in pregnancy, WHO recommends the use of BNT162b2 in pregnant individuals. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
Vaccine effectiveness is expected to be similar in breastfeeding women as in other adults. WHO recommends the use of the vaccine in breastfeeding women as in other adults. WHO does not recommend discontinuing breastfeeding because of vaccination. Vaccine-elicited antibodies have been found in breast milk following vaccination of breastfeeding women, suggesting possible neonatal as well as maternal protection.
Who should not take the vaccine?
People with a history of severe allergic reaction to any component of the vaccine should not take it.
Anyone with fever (body temperature over 38.5 ºC) should postpone vaccination until they are afebrile.
Is this vaccine recommended for children and adolescents?
This vaccine is authorized for use for those aged 6 months and older, with an adjustment in the recommended dosage for those aged 6 months to 4 years, and an adjustment for those aged 5-11 years.
WHO recommends that countries should consider using the vaccine in children aged 6 months and older to 17 only when high vaccine coverage with 2 doses has been achieved in the highest and high priority-use groups as identified in the WHO Prioritization Roadmap.
In accordance with the WHO Prioritization Roadmap, the priority remains to prevent deaths by achieving high vaccine coverage (primary series and boosters) in the highest and high priority-use groups.
In general, children are at lower risk of COVID-19. That is why WHO recommend that countries prioritize vaccinating people who have higher risk first, like people who are older, have existing health conditions and health workers.
Is it safe?
The Global Advisory Committee on Vaccine Safety (GACVS), a group of experts that provides independent and authoritative guidance to WHO on the topic of safe vaccine use, receives and assesses reports of suspected safety events of potentially international impact. In October 2021, the GACVS COVID-19 subcommittee concluded that the mRNA COVID-19 vaccines have clear benefits in all age groups in reducing hospitalizations and deaths due to COVID-19.
A very rare serious adverse event is myocarditis, which is mainly observed in young males aged 18-35 after the second dose. These myocarditis cases typically occurred within a few days after vaccination, are generally mild, respond to conservative treatment, and are less severe with better outcomes than classical myocarditis or COVID-19 related myocarditis.
How efficacious is the vaccine?
The Pfizer BioNTech vaccine against COVID-19 has very high efficacy against severe disease and moderate efficacy against symptomatic SARS-CoV-2 infection.
What is the recommended dosage?
For all persons aged 12 years and above, SAGE recommends two doses (30 µg, 0.3 ml each), 4-8 weeks apart given intramuscularly into the deltoid muscle.
For children aged 5 to 11 years SAGE recommends two doses (10 µg, 0.2 ml each) given intramuscularly into the deltoid muscle and provided 4-8 weeks apart, preferentially 8 weeks.
For infants and children aged 6 months to 4 years, the recommended schedule is three doses (3µg, 0.2 ml each): a schedule of two doses 3 weeks apart followed by a third dose at least 8 weeks after the second dose are recommended according to the label. However, countries could consider extending the interval between the first and second dose up to 8 weeks.
Compliance with the full schedule is recommended and the same product can be used for both doses.
SAGE recommends that severe and moderately immunocompromised persons, including children, should be offered an additional dose of vaccine, as part of the primary series. This is due to the fact that this group is less likely to respond adequately to vaccination following a standard primary vaccination series and are at higher risk of severe COVID-19 disease.
Is a booster dose recommended for this vaccine?
The first booster dose is recommended for the highest priority-use groups (e.g. older adults, persons with moderate to severe immunocompromising conditions, and health workers) followed by lower priority-use groups, 4-6 months after the completion of the primary series. If more than 6 months have elapsed since completion of the primary series, the booster dose should be given at the earliest opportunity.
WHO recommends countries should consider a second booster dose 4-6 months after the first booster dose for the highest priority-use groups.
There is currently no recommendation for either first or second booster doses in children under the age of 12, except for children with immunocompromising conditions.
Can this vaccine be ‘mixed and matched’ with other vaccines?
SAGE accepts two doses from different COVID-19 vaccine platforms of WHO Emergency Use Listing (EUL) COVID-19 vaccines as a complete primary series.
For countries considering mix-and match schedules, WHO has made recommendations to ensure equivalent or favourable immunogenicity or vaccine effectiveness for heterologous versus homologous schedules:
Does it prevent infection and transmission?
There is modest vaccine impact on transmission.
In the meantime, we must maintain and strengthen public health measures that work: masking, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds, and ensuring good ventilation.
Does it work against new variants?
The vaccine remains effective against virus variants, though for the Omicron variant, vaccine effectiveness against severe and mild disease after two doses is lower compared to Delta, and waning is more rapid. Therefore, a third dose (first booster) is recommended for all adults, and a second booster for the highest priority-use groups.
How does this vaccine compare to other COVID-19 vaccines in use?
It is impossible to compare vaccines head-to-head due to the different approaches taken in designing the respective studies, but overall, all of the vaccines that have achieved WHO Emergency Use Listing are highly effective in preventing severe disease and hospitalization due to COVID-19.
This webpage was updated on 18 August 2022 to reflect the latest guidance.
This webpage was updated on 19 January 2022 to include the latest guidance.
This webpage was updated on 5 January 2022 to update the latest guidance and ensure consistency of information and formatting.
This webpage was updated on 20 April 2021 to ensure consistency of information and formatting.
This article was corrected on 12 January 2021 to remove an erroneous reference relating to pregnancy. WHO does NOT recommend that pregnancy be avoided post-vaccination.
This article was corrected on 10 June to assure consistency of formatting.
The Sinopharm COVID-19 vaccine: What you need to know
Updated on 10 June 2022, pursuant to revised interim recommendations.
Here is what you need to know.
Who can be vaccinated?
The vaccine is safe and effective for all individuals aged 18 and above. In line with the WHO Prioritization Roadmap and the WHO Values Framework, older adults, health workers and immunocompromised persons should be prioritised.
The Sinopharm vaccine can be offered to people who have had COVID-19 in the past. But individuals may choose to delay vaccination for 3 months following the infection.
Should pregnant and breastfeeding women be vaccinated?
The available data on the COVID-19 vaccine Sinopharm in pregnant women are insufficient to assess either vaccine efficacy or vaccine-associated risks in pregnancy. However, this vaccine is an inactivated vaccine with an adjuvant that is routinely used in many other vaccines with a documented good safety profile, including in pregnant women. The effectiveness of the COVID-19 vaccine Sinopharm in pregnant women is therefore expected to be comparable to that observed in non-pregnant women of similar age.
In the interim, WHO recommends the use of the COVID-19 vaccine Sinopharm in pregnant women when the benefits of vaccination to the pregnant woman outweigh the potential risks. To help pregnant women make this assessment, they should be provided with information about the risks of COVID-19 in pregnancy; the likely benefits of vaccination in the local epidemiological context; and the current limitations of safety data in pregnant women. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or considering terminating pregnancy because of vaccination.
Vaccine effectiveness is expected to be similar in breastfeeding women as in other adults. WHO recommends the use of the COVID-19 vaccine Sinopharm in breastfeeding women as in other adults. WHO does not recommend discontinuing breastfeeding after vaccination.
Who is the vaccine not recommended for?
Individuals with a history of anaphylaxis to any component of the vaccine should not take it.
Anyone with a body temperature over 38.5ºC should postpone vaccination until they no longer have a fever.
Is it safe?
SAGE has thoroughly assessed the data on quality, safety and efficacy of the vaccine and has recommended its use for people aged 18 and above.
Safety data are limited for persons above 60 years of age (due to the small number of participants in clinical trials). While no differences in safety profile of the vaccine in older adults compared to younger age groups can be anticipated, countries considering using this vaccine in persons older than 60 years should maintain active safety monitoring.
How efficacious is the vaccine?
A large multi-country Phase 3 trial has shown that 2 doses, administered at an interval of 21 days, have an efficacy of 79% against symptomatic SARS-CoV-2 infection 14 or more days after the second dose. Vaccine efficacy against hospitalization was 79%.
The trial was not designed and powered to demonstrate efficacy against severe disease in persons with comorbidities, in pregnancy, or in persons aged 60 years and above. Women were underrepresented in the trial. The median duration of follow-up available at the time of evidence review was 112 days.
Two other efficacy trials are under way but data are not yet available.
What’s the recommended dosage?
SAGE recommends the use of Sinopharm vaccine as 2 doses (0.5 ml) given intramuscularly.
SAGE recommends that a third, additional dose of the Sinopharm vaccine be offered to persons aged 60 and above as part of an extension of the primary series. Current data does not indicate the need for an additional dose in persons under 60 years of age.
SAGE recommends that severe and moderately immunocompromised persons should be offered an additional dose of vaccine. This is due to the fact that this group is less likely to respond adequately to vaccination following a standard primary vaccination series and are at higher risk of severe COVID-19 disease.
WHO recommends an interval of 3–4 weeks between the first and second dose of primary series. If the second dose is administered less than 3 weeks after the first, the dose does not need to be repeated. If administration of the second dose is delayed beyond 4 weeks, it should be given at the earliest possible opportunity. When administering an additional dose to over 60s, SAGE recommends countries should initially aim at maximizing 2-dose coverage in that population, and thereafter administer the third dose, starting with the oldest age groups.
Is a booster dose recommended for this vaccine?
A booster dose may be considered 4 – 6 months after completion of the primary vaccination series, starting with the higher priority-use groups, in accordance with the WHO Prioritization Roadmap.
The benefits of booster vaccination are recognized following increasing evidence of waning vaccine effectiveness against mild and asymptomatic SARS-CoV-2 infection over time.
Either homologous (a different vaccine product to Sinopharm) or heterologous (a booster dose of Sinopharm) doses can be used. A study in Bahrain found that heterologous boosting resulted in a superior immune response compared to homologous boosting.
Can this vaccine be ‘mixed and matched’ with other vaccines?
SAGE accepts two heterologous doses of WHO EUL COVID-19 vaccines as a complete primary series.
To ensure equivalent or favourable immunogenicity or vaccine effectiveness either of the WHO EUL COVID-19 mRNA vaccines (Pfizer or Moderna) or the WHO EUL COVID-19 vectored vaccines (AstraZeneca Vaxzevria/COVISHIELD or Janssen) can be used as a second dose following a first dose with the Sinopharm vaccine dependent on product availability.
Does it prevent infection and transmission?
There is currently no substantive data available related to the impact of Sinopharm on transmission of SARS-CoV-2, the virus that causes COVID-19 disease.
In the meantime, WHO reminds of the need to maintain and strengthen public health measures that work: masking, physical distancing, handwashing, respiratory and cough hygiene, avoiding crowds and ensuring adequate ventilation.
Does it work against new variants of SARS-CoV-2 virus?
SAGE currently recommends using this vaccine, according to the WHO Prioritization Roadmap.
As new data becomes available, WHO will update recommendations accordingly. This vaccine has not yet been evaluated in the context of circulation of widespread variants of concern.
How does this vaccine compare to other vaccines already in use?
We cannot compare the vaccines head-to-head due to the different approaches taken in designing the respective studies, but overall, all of the vaccines that have achieved WHO Emergency Use Listing are highly effective in preventing severe disease and hospitalization due to COVID-19.
This webpage was updated on 10 June 2022 to update the latest guidance and ensure consistency of information and formatting.
20 August 2021 | Science conversation
Summary
Podcast
Transcript
Vismita Gupta-Smith
If you have COVID-19, do you still need to get vaccinated? How long should you wait before vaccination? Hello and welcome to Science in 5. I’m Vismita Gupta-Smith and these are WHO’s conversations in science. We are talking to WHO’s Chief Scientist, Dr. Soumya Swaminathan. Welcome Soumya. Let’s start with if I have COVID-19, do I still need to get vaccinated?
Dr. Soumya Swaminathan
After getting COVID, people do get an immune response, but this varies from person to person and it depends on whether you had a mild infection or whether you had more severe infection. And we know from many studies now that if you’ve had a very mild or asymptomatic infection, then many people may have very low levels of antibodies that they form. So this is why we still recommend that even if you’ve had COVID infection, that you should go ahead and take the vaccination when it’s available to you, because the vaccine then serves as a boost to the immune system. After getting COVID, people do get an immune response, but this varies from person to person and it depends on whether you had a mild infection or whether you had more severe infection. And we know from many studies now that if you’ve had a very mild or asymptomatic infection, then many people may have very low levels of antibodies that they form. So this is why we still recommend that even if you’ve had COVID infection, that you should go ahead and take the vaccination when it’s available to you, because the vaccine then serves as a boost to the immune system.
Vismita Gupta-Smith
Soumya, how long should I wait after a COVID infection to get vaccinated?
Dr. Soumya Swaminathan
Well, you can take the vaccine actually, once you’ve recovered from COVID. So waiting for a few weeks is recommended. You should have no symptoms at all and you should feel perfectly well when you take your vaccination. However, there are differences between countries. Some countries recommend that people wait for three months or six months till after the infection. And this is because you have natural antibodies which will keep you protected for at least that long. And because there are shortages of vaccine supplies in many countries, they are requesting people who’ve had the infection to wait for three or six months. But from a scientific and a biological point of view, you can take the vaccine as soon as you’ve fully recovered from COVID. At this point of time, we are not sure of exactly the level of neutralizing antibodies that offer protection against an infection. And therefore, we do not recommend that individuals go and get antibody testing done in order to confirm whether they have immunity or not. We have to wait again for more data on what the correlate of protection is.
Vismita Gupta-Smith
Soumya, what have we learned so far about immunity that is induced after an infection of COVID-19 versus immunity induced by the vaccines?
Dr. Soumya Swaminathan
Vismita Gupta-Smith
Thank you Soumya, that was Science in 5 today. Until next time then. Stay safe, stay healthy and stick with science.
The Bharat Biotech BBV152 COVAXIN vaccine against COVID-19: What you need to know
Updated on 10 June 2022, pursuant to revised interim recommendations.
On 3 November 2021, the Technical Advisory Group for Emergency Use Listing listed the Bharat Biotech BBV152 COVAXIN vaccine against COVID-19 for emergency use. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has issued interim policy recommendations for the use of the Bharat Biotech BBV152 COVAXIN vaccine. This article provides a summary of those interim recommendations.
Who can take this vaccine?
The vaccine is safe and effective for all individuals aged 18 and above. In line with the WHO Prioritization Roadmap and the WHO Values Framework, older adults, health workers and immunocompromised persons should be prioritised.
This vaccine can be offered to people who have had COVID-19 in the past. But individuals may choose to delay vaccination for 3 months following the infection.
Should pregnant and breastfeeding women be vaccinated?
Given the adverse consequences of COVID-19 disease during pregnancy, WHO recommends the use of BBV152 in pregnant individuals when the benefits of vaccination to the pregnant person outweigh the potential risks. WHO does not recommend pregnancy testing prior to vaccination. WHO does not recommend delaying pregnancy or terminating pregnancy because of vaccination.
WHO recommends the same use of BBV152 vaccine in breastfeeding and non-breastfeeding women. Data are not available on the potential benefits or possible risks of the BBV152 vaccine to breastfed children. However, as BBV152 vaccine is not a live virus vaccine, it is biologically and clinically unlikely to pose a risk to the breastfeeding child. WHO does not recommend discontinuing breastfeeding because of vaccination.
Who is the vaccine not recommended for?
The vaccine is not recommended for people younger than 18 years of age. Safety and immunogenicity data for under-18s are currently being generated but until such data are available, vaccination of individuals in this age group is not recommended.
Individuals with a history of anaphylaxis to any component of the vaccine should not take it.
Persons with acute PCR-confirmed COVID-19 should not be vaccinated until after they have recovered from acute illness and the criteria for ending isolation have been met.
Anyone with a body temperature over 38.5°C should postpone vaccination until they no longer have a fever.
Is it safe?
SAGE has thoroughly assessed the data on safety and efficacy of the vaccine and has recommended its use for people aged 18 and above. The WHO EUL process also evaluates the quality of manufacturing along with safety and efficacy.
Safety data is currently limited for persons above 60 years of age (due to the small number of participants of this age group in clinical trials). However, the trial data indicate that the vaccine has an acceptable safety profile for this age group and WHO recommends the vaccine for use in persons aged 60 years and over.
BBV152 has been licensed for use in 23 countries globally; however roll-out has been limited mostly to India where over 77 million doses have been distributed and used. Vaccine effectiveness studies are being conducted in India, and results will be available in the coming months.
How efficacious is the vaccine?
Vaccine efficacy against COVID-19 of any severity, 14 or more days post dose 2, was 78%. Vaccine efficacy against severe disease is 93%. In adults aged less than 60 years, efficacy was 79%; and in those aged 60 years and over it was 68%.
What is the recommended dosage?
SAGE recommends the use of BBV152 vaccine as 2 doses (0.5 ml) given intramuscularly. The vaccine can be administered with an interval of 4 weeks. It is recommended that all vaccinated individuals receive two doses.
If the second dose is inadvertently administered less than 4 weeks after the first, the dose does not need to be repeated. If administration of the second dose is delayed beyond 4 weeks, it should be given at the earliest possible opportunity.
SAGE recommends that severe and moderately immunocompromised persons should be offered an additional dose of vaccine. This is due to the fact that this group is less likely to respond adequately to vaccination following a standard primary vaccination series and are at higher risk of severe COVID-19 disease.
Is a booster dose recommended for this vaccine?
A booster dose may be offered 4-6 months after completing the primary series for the highest-risk groups, for example, older adults, health workers, persons with comorbidities. In line with the SAGE Prioritization Roadmap, WHO recommends countries should prioritize booster coverage amongst higher priority-use groups before offering vaccine doses to lower priority-use groups.
The benefits of booster doses are recognized following increasing evidence of waning vaccine effectiveness against mild and asymptomatic SARS-CoV-2 infection over time.
Can this vaccine be ‘mixed and matched’ with other vaccines?
SAGE accepts two heterologous doses of WHO EUL COVID-19 vaccines as a complete primary series.
To ensure equivalent or favourable immunogenicity or vaccine effectiveness either of the WHO EUL COVID-19 mRNA vaccines (Pfizer or Moderna) or the WHO EUL COVID-19 vectored vaccines (AstraZeneca Vaxzevria/COVISHIELD or Janssen) can be used as a second dose following a first dose with the Bharat COVID-19 vaccine dependant on product availability.
Does it prevent infection and transmission?
Vaccine efficacy against asymptomatic SARS-CoV-2 infection was 64%.
As there is not currently sufficient evidence to date to evaluate the impact of the vaccine on transmission, public health and social measures must continue, including use of face masks, physical distancing, handwashing, appropriate ventilation, and other measures as appropriate in particular settings, depending on the COVID-19 epidemiology and potential risks of emerging variants. Government advice on public health and social measures should continue to be followed by both vaccinated and unvaccinated individuals. SAGE will update this advice as information on the impact of vaccination on virus transmission and indirect protection is assessed.
Does it work against new variants of SARS-CoV-2 virus?
Vaccine efficacy against all variant-related COVID-19 disease was 71% with an efficacy of 90% against Kappa, and 65% against Delta. In view of these findings, WHO recommends the use of BBV152 vaccine according to the WHO Prioritization Roadmap, even if currently recognized Variants of Concern (VOC) are present in the country. If new VOCs emerge for which vaccine performance is compromised, these recommendations will be updated accordingly. There are no data yet for Omicron.
How does this vaccine compare to other COVID-19 vaccines already in use?
It is impossible to compare the vaccines head-to-head due to the different approaches taken in designing the respective studies, but overall, all of the vaccines that have achieved WHO Emergency Use Listing are highly effective in preventing severe disease and hospitalization due to COVID-19.
This webpage was updated on 10 June 2022 to ensure consistency of formatting.
This webpage was updated on 16 March 2022 to reflect the latest guidance.
This webpage was updated on 5 January 2022 to update the latest guidance and ensure consistency of information and formatting.
Interim statement on COVID-19 vaccination for children and adolescents
This statement was updated on 29 November 2021 to correct some references and associated links
Background
Although the majority of COVID-19 vaccines are only approved for use in adults aged 18 years and above, an increasing number of vaccines are now also being authorized for use in children. Some countries have given emergency use authorization for mRNA vaccines for use in the adolescent age group (aged 12-17 years): BNT162b2 developed by Pfizer, and mRNA 1273 developed by Moderna. In November 2021, one stringent regulatory authority approved the mRNA vaccine BNT162b2 for the use in children aged 5-11. Trials in children as young as age 3 years were completed for two inactivated vaccines (Sinovac-CoronaVac and BBIBP-CorV) and these products were approved by Chinese authorities for the age indication of 3-17 years; although these vaccine products have received EUL for adults, they have not yet received WHO EUL for children. Covaxin, an adjuvanted inactivated vaccine developed by Bharat, was approved in India for the age indication of 12-17 years; but not yet received WHO EUL for this age indication. The Indian regulatory authorities have given approval to ZycovD, a novel DNA vaccine, for ages 12-17 years; however, this vaccine has not yet received WHO EUL. Several COVID-19 vaccines are undergoing trials in younger age groups (including as young as 6 months of age), but results have not yet been published.
The greatest burden of disease in terms of severe disease and deaths remains among older persons and those with comorbidities, the evidence of which led to the WHO Prioritization Roadmap which identifies high priority-use groups according to vaccine supplies available to countries(1). WHO recognizes that various countries are in different pandemic phases with different vaccination coverage rates. The WHO global vaccination strategy targets remain: 40% of each country’s population by end of 2021, and 70% by mid-2022(2). These coverage targets were set to ensure an equitable pace of global vaccine rollout & prioritization of those at highest risk. To date, these targets have not yet been achieved.
This interim statement examines the role of COVID-19 vaccines in adolescents and children in the global context of inequitable vaccine distribution across countries and globally limited vaccine supply.
Burden of disease in children and adolescents
Overall, there are proportionally fewer symptomatic infections, and cases with severe disease and deaths from COVID-19 in children and adolescents, compared with older age groups. Age-disaggregated cases reported to WHO from 30 December 2019 to 25 October 2021(3) show that children under five years of age represent 2% (1 890 756) of reported global cases and 0.1% (1 797) of reported global deaths. Older children and younger adolescents (5 to 14 years) account for 7% (7 058 748) of reported global cases and 0.1% (1 328) of reported global deaths while older adolescents and young adults (15 to 24 years) represent 15% (14 819 320) of reported global cases and 0.4% (7 023) of reported global deaths. Deaths for all ages less than 25 years represented less than 0.5% of reported global deaths.
Children and adolescents usually demonstrate fewer and milder symptoms of SARS-CoV-2 infection compared to adults and are less likely than adults to experience severe COVID-19(4). Milder symptoms and asymptomatic presentations may mean less frequent care seeking in these groups, thus children and adolescents tend to be tested less and cases may go unreported. An age-dependent risk of severe disease with those under one year of age experiencing more severe disease has been suggested(5, 6), although several reviews show that neonates (infants in the first 28 days of life) have mild disease when compared with other paediatric patients(7, 8). It is important to note that children under the age of five years have a higher risk of other diseases with clinical presentations that overlap with COVID-19, such as pneumonia and other viral upper respiratory tract infections, which may lead to misclassification. Additionally, age disaggregation has not been systematically provided in the literature, and the results of these studies are context-specific depending on factors such as timing within the pandemic and an emphasis on hospitalized patients(6).
Children and adolescents can experience prolonged clinical symptoms (known as “long COVID-19”, post COVID-19 condition(9), or post-acute sequelae of SARS-CoV-2 infection), however, the frequency and characteristics of these conditions are still under investigation. Additionally, a hyperinflammatory syndrome, referred to as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in Europe and multisystem inflammatory syndrome in children (MIS-C) in the United States, although rare, has been reported to occur world-wide and complicate recovery from COVID-19(10).
Several risk factors for severe COVID-19 in children have been reported recently, including older age, obesity, and preexisting conditions. The preexisting conditions associated with higher risk of severe COVID-19 include type 2 diabetes, asthma, heart and pulmonary diseases, and neurologic, neurodevelopmental (in particular, Down Syndrome) and neuromuscular conditions(11).
The preponderance of evidence on the risk for severe COVID-19 and death in children and adolescents comes from studies in high resource settings, so the applicability of the following observations to lower resource settings remains to be determined. One systematic review suggests that there may be larger impact of paediatric COVID-19 related fatality in low to middle income countries versus high income countries (12).
The role of children and adolescents in transmission of SARS-CoV-2
Outbreaks of COVID-19 have been identified in secondary schools, summer camps and day care centres, particularly when neither physical distancing nor masks were used to reduce infection transmission risk. There is some preliminary evidence that younger children may be less infectious, as measured by secondary attack rates, than adolescents and adults(14). Data on the global incidence of COVID-19 suggest adolescents test positive for SARS-CoV-2 at a higher proportion than younger children, however seroprevalence surveys are required to provide more conclusive information on infection rates.
Children who become infected with SARS-CoV-2 shed the virus in their respiratory tract and also in their faeces(15). Amongst individuals positive for SARS-CoV-2 who were tested at the same time point after symptom onset, levels of SARS-CoV-2 viral RNA shedding in the respiratory tract appeared similar in children, adolescents, and adults(16).
The relationship between age, viral load, and transmission across the full symptom spectrum of SARS-CoV-2 infection has not been comprehensively investigated because people with no, or mild symptoms are seldom tested systematically. The relative transmissibility of SARS-CoV-2 at different ages remains uncertain, largely due to the challenges involved in disentangling the influences of biological, host, virus, variants of concern, and environmental factors(17).
Socio-economic impact of the COVID-19 pandemic and pandemic response on children and adolescents
Despite their lower risk of severe COVID-19 disease, children and adolescents have been disproportionately affected by COVID-19 control measures. The most important indirect effects are related to school closures which have disrupted the provision of educational services and increased emotional distress and mental health problems. When unable to attend school and in social isolation, children are more prone to maltreatment and sexual violence, adolescent pregnancy, and child marriage, all of which increase the probability of missing further education and of poor pregnancy outcomes. A range of follow-on effects of school closures occur. These include disruption in physical activity and routines and loss of access to a wide range of school-provided services such as school meals, health, nutrition, water, sanitation and hygiene (WASH) and services targeted to children with special needs such as learning support, speech therapy and social skills training. Children not attending school face enhanced risks of cyberbullying from other children, and the potential for predatory behavior from adults related to spending more time online. Longer-term, prolonged school closures lead to education loss and exacerbation of pre-existing inequalities and marginalization of learning. It is estimated that 24 million children are at risk of not returning to school owing to the pandemic(18); those affected have been estimated to incur a US$10 trillion loss in lifetime earnings (19). At societal level, economic devastation wrought by COVID-19 may take years to overcome, exacerbating economic inequalities, poverty, unemployment, household financial insecurity, food insecurity, and malnutrition, all of which negatively impact children, often disproportionately. Routine immunization services have also been negatively affected as a result of the pandemic response, thereby exacerbating the potential resurgence of vaccine-preventable diseases such as measles, tetanus, yellow fever, HPV, and others(20).
Efficacy and safety of COVID-19 vaccines in adolescents and children
In Phase 2/3 trials for both mRNA vaccines, efficacy and immunogenicity were similar or higher compared to adults; safety and reactogenicity profiles in adolescents were similar to young adults. A very rare signal of myocarditis/pericarditis has been reported with mRNA COVID-19 vaccines as some countries have started to use these vaccines in their COVID-19 programmes. These cases occurred more often in younger men (16-24 years of age) and after the second dose of the vaccine, typically within a few days after vaccination. As the mRNA vaccines are just being rolled out in adolescents in some countries, the risk of myocarditis in that age group has not yet been fully determined. Available data suggest that the cases of myocarditis and pericarditis following vaccination are generally mild and respond to conservative treatment, and are less severe with better outcomes than classical myocarditis or COVID-19. The risk of myocarditis/pericarditis associated with SARS-CoV-2 infection is higher than the risk after vaccination(21). In October 2021, the Global Advisory Committee on Vaccine Safety (GACVS) concluded that in all age groups the benefits of mRNA COVID-19 vaccines in reducing hospitalizations and deaths due to COVID-19 outweigh the risks. The risk of Thrombosis with Thrombocytopenia Syndrome (TTS) following adenoviral-vector vaccines, although overall low, was higher in younger adults compared to older adults, but no data are available on the risk below the age of 18 years.
Global equity and public health goals
In the context of ongoing global COVID-19 vaccine supply constraints, the focus of immunization programs must remain on protecting sub-populations at highest risk of hospitalizations and deaths, according to the WHO Prioritization Roadmap. There is now overwhelming evidence that immunisation of all adults with COVID-19 vaccines provides important health returns on investment. Adult immunisation is feasible in all countries with the right investments and is being actively pursued in almost all countries. However, the benefits of vaccinating children to reduce the risk of severe disease and death are much less than those associated with vaccinating older adults. Countries with few or no vaccine supply constraints should consider the issues of global equity when making policy decisions about vaccinating children and adolescents. Any guidance on vaccine use prioritization, including booster dose policy, cannot ignore the current, on-going profound inequities in global vaccine access. While higher-income countries expand their vaccination programmes to adolescents, children, and, in some countries, booster doses to a large proportion of their populations, many lower-income countries still lack sufficient vaccine supply to offer a primary vaccination series to their highest priority-use groups, including older adults and health care workers who comprise only a small proportion of their populations.
Rationale for vaccinating adolescents and children
Vaccines which have received authorization by stringent regulatory authorities for the age indication of children and adolescents are safe and effective in reducing disease burden in these age groups.
Although benefit-risk assessments clearly underpin the benefit of vaccinating all age groups, including children and adolescents, the direct health benefit of vaccinating children and adolescents is lower compared with vaccinating older adults due to the lower incidence of severe COVID-19 and deaths in younger persons. Safety signals identified after widespread roll-out, such as myocarditis, albeit rare, are reported more frequently in young persons aged 16-24 years, particularly males; the risk of myocarditis in adolescents and/or children has not yet been determined.
Reducing intergenerational transmission is an important additional public health objective when vaccinating children and adolescents. Prior to the emergence of the delta variant, it was reported that the risk of symptomatic cases in household contacts of vaccinated cases was about 50% lower than that among household contacts of unvaccinated cases(22). However, the impact of vaccination on reducing transmission in the context of the more transmissible delta variant appears to be lower(23). Teachers, family members, and other adult contacts of children and adolescents should all be vaccinated.
Vaccinating children and adolescents may also help advance other highly valued societal goals. Maintaining education for all school-aged children should be an important priority during this pandemic. School attendance is critical to the well-being and life prospects of children and to parental participation in the economy. Vaccinating school-aged children may help minimize school disruptions by reducing the number of infections at school and the number of children required to miss school because of quarantine requirements.
The benefit of vaccinating children and adolescents may be lower in settings with high seropositivity rates in that age group, however, more evidence is needed on seroprevalence of school-aged children.
Conclusions
Countries should consider the individual and population benefits of immunising children and adolescents in their specific epidemiological and social context when developing their COVID-19 immunisation policies and programs. As children and adolescents tend to have milder disease compared to adults, unless they are in a group at higher risk of severe COVID-19, it is less urgent to vaccinate them than older people, those with chronic health conditions and health workers.
There are benefits of vaccinating children and adolescents that go beyond the direct health benefits. Vaccination that decreases COVID transmission in this age group may reduce transmission from children and adolescents to older adults, and may help reduce the need for mitigation measures in schools. Minimizing disruptions to education for children and maintenance of their overall well-being, health and safety are important considerations. Countries’ strategies related to COVID-19 control should facilitate children’s participation in education and other aspects of social life, and minimize school closures, even without vaccinating children and adolescents (24). UNICEF and WHO have developed guidance on how to minimize transmission in schools and keep schools open, regardless of vaccination of school-aged children(25).
As a matter of global equity, as long as many parts of the world are facing extreme vaccine shortages, countries that have achieved high vaccine coverage in their high-risk populations should prioritize global sharing of COVID-19 vaccines through the COVAX facility before proceeding to vaccination of children and adolescents who are at low risk for severe disease.
It is of utmost importance for children to continue to receive the recommended childhood vaccines for other infectious diseases.
COVID-19 vaccines
When medicines are under rolling review, EMA’s human medicines committee (CHMP) evaluates clinical trial data as soon as these become available until it decides there is enough evidence for the developer to apply for marketing authorisation.
EMA cannot provide exact timelines as these depend on when developers provide the necessary data for CHMP review.
Information on COVID-19 vaccines that are no longer under rolling review following withdrawal from the process is available at COVID-19 vaccines under evaluation: Withdrawn from rolling review.
Once authorised, COVID-19 vaccines can be adapted to provide better protectin against a specific variant or variants of the SARS-CoV-2 virus.
EMA is not involved in advising on travel requirements in the European Union (EU), such as vaccination, quarantine or testing for travellers.
Decisions about which COVID-19 vaccines are included, for example, in the EU Digital COVID Certificate, are taken by the EU Member States. EMA is in charge of the scientific evaluation of vaccines for EU marketing authorisation. The acceptability criteria for travel purposes are broader and can include, for example, World Health Organization (WHO) listed vaccines that have not necessarily undergone the EMA process of authorisation.
Official information on this topic is available in all EU languages at:
WHO Vaccine Position Papers
In accordance with its mandate to provide guidance to Member States on health policy matters, WHO publishes vaccine position papers providing global vaccine and immunization recommendations for diseases that have an international public health impact. The papers summarize essential background information on the respective diseases and vaccines, and conclude with the current WHO position concerning their use in the global context.
The papers are designed for use by national public health officials and immunization programme managers. They may also be of interest to international funding agencies, the vaccine manufacturing industry, the medical community, and the scientific media.
WHO Position Paper Process
WHO Vaccine Position Paper Process
WHO position papers follow the recommendations of the WHO Strategic Advisory Group of Experts (SAGE) on immunization and undergo a formal review process both internally and externally prior to publication. Processes to manage potential conflicts of interest and to ensure careful and critical appraisal of the best scientific evidence have become more rigorous in recent years. A register of interests of SAGE members is maintained by WHO with summaries of interests declared relevant to SAGE topics published on the SAGE web site.
The position papers are published in the Weekly Epidemiological Record in English and French and translated into the other WHO official languages: Arabic, Chinese, Russian, and Spanish. Each position paper is now accompanied by a summary in both text and slide formats, a list of key references, and tables of grading of scientific evidence.
The need for updating vaccine position papers is reviewed periodically and depends primarily on the availability of new scientific evidence and public health priorities. A brief update concerning a specific recommendation in a paper is released when warranted.
COVID-19 vaccines: key facts
Table of contents
The European Medicines Agency (EMA) helps ensure that COVID-19 vaccines offer continued protection against the SARS-CoV-2 coronavirus, including variants such as Delta and Omicron, by working with European Union (EU) and international partners. The information below explains how EMA evaluates data and makes recommendations on the protection provided by vaccines, their safety, vaccination in children, boosters and related topics.
Virus variants
The COVID-19 vaccines authorised in the EU do protect against severe disease and death caused by variants of the SARS-CoV-2 virus. These include Omicron and its sub-variants, which are spreading across many countries.
Vaccines still play a crucial role in preventing severe COVID-19 disease: unvaccinated people remain at much higher risk of falling severely ill with COVID-19, compared to people who have been vaccinated.
While the level of protection from COVID-19 vaccines tends to get less over time, people who have had a booster dose are less likely to develop severe disease or to die from infection with Omicron than people who have only received their ‘primary course’.
EMA continues to work very closely with the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) to assess how well vaccination protects against the Omicron variant, and its impact on the number of people who die or need to go into hospital.
EMA is currently evaluating COVID-19 vaccines adapted to provide improved protection against virus variants.
The Agency relies on clinical trials to assess whether the protection offered by these adapted vaccines is at least comparable to the protection offered by the currently authorised vaccines.
EMA expects that the first adapted mRNA vaccines will be authorised in the EU in the autumn of 2022. It is working closely with international partners to facilitate the availability of adapted vaccines.
Each EU Member State will be responsible for deciding how to use the adapted COVID-19 vaccines as part of their national vaccination campaigns.
The current vaccines, including the recommended booster doses, remain critical in preventing severe disease, hospitalisation and death caused by COVID-19.
EMA follows the emergence and spread of new variants and monitors the effectiveness of vaccines at all times. It requires all vaccine developers to investigate if their vaccines protect against emerging variants, and to provide their findings to EMA for assessment.
For more information, see:
Infections in vaccinated people are not unexpected. They can happen partly due to the decrease in initial protection offered by the primary (initial) vaccination course over time, the emergence of more transmissible variants that are better at escaping the body’s immune system, and changing social measures such as distancing and mask wearing.
No vaccine is 100% effective. Some vaccinated people may still develop severe COVID-19 and be hospitalised, or even die, particularly those with underlying health conditions.
As infection rates increase, more vaccinated people may get infected and develop COVID-19. But authorised vaccines offer a high level of protection against hospitalisation and death.
So far, in Europe, authorised vaccines are estimated to have saved hundreds of thousands of lives among people aged 60 years and over.
For more information, see:
People who have been vaccinated can still catch the SARS-CoV-2 virus. The longer it is since someone was vaccinated, the greater the chance of infection, especially with highly infectious variants such as Omicron and its sub-variants.
Vaccinated people who catch the virus are far less likely to fall severely ill, to be admitted to hospital or to die than unvaccinated people.
People who have been vaccinated can still pass on the SARS-CoV-2 virus to others.
However, studies show people who have been fully vaccinated and have received a booster are less likely to pass the virus to others compared with unvaccinated people.
Immunity (protection)
There is evidence that protection against infection and particularly against mild disease decreases around six months after primary vaccination. However, because protection against severe disease lasts longer, in the EU most cases of severe disease occur in unvaccinated people.
At present, it is not known how long immunity (protection) against COVID-19 will last after the booster dose.
The duration of immunity is influenced by several factors. For instance, immunity drops faster in men, older people and those with other health problems.
People with weak immune systems may need an additional dose as part of their primary (initial) vaccination to be properly protected against COVID-19.
Studies in organ transplant patients with weak immune systems have shown that an additional dose increases the ability to produce antibodies against SARS-Cov-2. Based on a review, EMA has advised that an additional dose should be given to people with a severely weakened immune system.
EMA continues to evaluate new evidence on additional doses with all COVID-19 vaccines in people with weak immune systems.
Vaccines protect from infection and serious disease. They have reduced the impact of the SARS-CoV-2 virus and remain a crucial tool to fight the pandemic.
Some medicines to treat or prevent COVID-19 have been authorised in the EU, following evaluation by EMA.
These medicines complement vaccines in the fight against COVID-19, but do not replace them.
They provide another way to reduce the burden of disease associated with COVID-19 and prevent hospitalisation. They are particularly relevant for vulnerable groups and people who do not respond adequately to vaccination, or who cannot be vaccinated.
For more information, see:
Yes, people who have recovered from COVID-19 infection can still be vaccinated.
Studies suggest that people who had COVID-19 and were then vaccinated are better protected against reinfection than people who only have natural immunity.
Natural immunity (immunity following natural infection) decreases over time, so getting vaccinated helps develop a stronger ability to fight future infections and protect against serious disease.
Each EU Member State is responsible for deciding who is vaccinated and when, including people who have been infected.
Boosters and mixing vaccines
Boosters are essential to restore immunity (protection), particularly against severe disease. They also reduce COVID-19 hospitalisations and the risk of death.
For children under 12 years of age, boosters have not yet been recommended. EMA is currently evaluating the use of an mRNA booster dose in this age group.
A booster dose is recommended for adults and may be considered for adolescents over 12 years of age.
A second booster with an mRNA COVID-19 vaccine should be considered for people aged 60 years and above, and for vulnerable persons.
EMA assesses the benefits and risks of boosters. However, EMA does not decide how or when boosters are given to people in EU countries (see also the section ‘Differences across the EU’).
For more information:
Yes, and they also provide high levels of antibodies in adults.
Currently, it is not known how long protection after a booster will last.
Recent evidence, including real-world effectiveness data, suggests that people who have had a booster dose appear to be better protected against the Omicron variant of SARS-CoV-2 than those who have only received their primary course vaccination.
Experience with vaccines against other diseases than COVID-19 has shown that some require several doses in order to ensure long-term protection (such as vaccines against hepatitis B). Others, like the vaccine against flu, need annual updates. This may become necessary with COVID-19 vaccines.
EMA will gain a better understanding of how long protection lasts, taking account of the spread of virus variants, as more data from vaccination campaigns and ongoing studies become available.
Using a different vaccine for the second dose, or as a booster dose, is safe and effective.
Most EU Member States have already decided to use a different vaccine for the second dose in their vaccination campaigns. For example, some countries have been offering people Comirnaty (developed by BioNTech and Pfizer) or Spikevax (developed by Moderna) after a first dose of Vaxzevria (developed by AstraZeneca).
The data currently available suggests that there is a satisfactory immune response with this approach, and that there are no safety concerns.
EMA is reviewing all new data on this topic as they become available to be able to make specific recommendations for each vaccine..
For more information, see:
Vaccination during pregnancy
Several studies have shown that mRNA COVID-19 vaccines do not cause complications of pregnancy in expectant mothers or their babies.
People who are pregnant or who might become pregnant soon are encouraged to receive COVID-19 vaccines in line with national recommendations.
People infected with SARS-CoV-2 while pregnant are more likely to become severely ill with COVID-19 than people who are not pregnant, especially in the second and third trimesters.
The information currently available on the use of COVID-19 vaccines during pregnancy mainly comes from studies looking at the mRNA vaccines Comirnaty and Spikevax. These studies involved more than 65,000 people who were at various stages of pregnancy.
The studies have not shown any signs that these COVID-19 vaccines increase the risk of complications of pregnancy, miscarriage, premature birth or harm to the unborn baby.
The data have also confirmed that the vaccines reduce the risk of hospitalisation and death in pregnant people, as they do in people who are not pregnant.
Side effects are similar to those seen in vaccinated people. They are mostly mild or moderate, and recede within a few days.
For more information, see:
Vaccination in children
COVID-19 is generally mild in children of all ages, although severe cases leading to hospitalisation do occur rarely. Children with an underlying illness are more likely than others to be admitted to hospital.
Current evidence indicates that the Omicron variant in circulation causes less severe disease than other variants but is more infectious. According to data from the European Centre for Disease Prevention and Control (ECDC), cases and hospitalisations of children with COVID-19 have increased in the EU after July 2021, including the period of time since Omicron started spreading.
ECDC has published interim considerations for vaccinating children 5-11 years old. An update on the effects of Omicron in children will be provided as further data become available.
For more information, see:
COVID-19 vaccines are as effective in children as they are in adults, as current evidence shows.
EMA evaluated data for using Comirnaty (developed by BioNTech / Pfizer) in children from 5 years of age and Spikevax (developed by Moderna) from 6 years of age. It found that antibody levels against SARS-CoV-2 after vaccination in children were comparable to those adults.
In addition, available evidence indicates that the immune response to a booster dose of Comirnaty in adolescents from 12 years of age is at least equal to that in adults.
Data on the effectiveness against the Omicron variant in children are still emerging. However, preliminary data from adults show COVID-19 vaccines remain effective against severe disease and hospitalisation caused by the Omicron variant.
There are currently limited data on how long protection in children lasts.
For more information, see:
COVID-19 vaccines are well tolerated in children, according to data from the United States where millions of children are have been vaccinated. EMA is assessing these and all other real-world data as they become available.
The side effects of these vaccines are usually mild or moderate and go away in a few days, based on clinical trials previously carried out in children. The most common side effects seen in trials were injection site reactions, nausea and vomiting.
Very rare cases of myocarditis and pericarditis (inflammatory conditions affecting the heart) have occurred in adolescents and adults after vaccination with mRNA vaccines. As with myocarditis or pericarditis unrelated to vaccination, these conditions usually recede following treatment.
EMA will continue monitoring data on safety in children as vaccinations continue.
For more information, see:
A company developing a COVID-19 vaccine must have a paediatric investigation plan (PIP) in place before their vaccine is authorised for adults. The plan outlines all the studies the company needs to carry out to support the vaccine’s authorisation in children.
EMA has evaluated studies carried out as part of PIPs. These include studies that looked at how well the vaccines triggered an immune response in children compared with adults, as well as safety and efficacy studies in children, involving up to 3,000 participants.
The Agency also considered the data from large studies in adults, including studies with up to 44,000 participants, and reports of side effects in adults. These may be relevant for children because of the similarities in how children and adults respond to vaccines.
EMA will continue evaluating data on these vaccines, including large amounts of real-world data on children from around the world.
In the EU, national authorities advise on vaccinating children as part of national vaccination campaigns in each country. They consider the overall situation in their country and the effects COVID-19 is having on different groups of people.
If you have any questions about vaccinating your child, you can also discuss these with a healthcare professional, particularly if your child has an underlying illness that puts them at higher risk of severe COVID-19.
More information on the use of COVID-19 vaccines, including in children where applicable, is available on the dedicated webpages for each authorised vaccine:
Differences across the EU
Each EU Member State is responsible for its own national COVID-19 vaccination campaign. This includes who should be vaccinated and when, when children should be vaccinated and who should get a booster.
Each country needs to take its own specific situation into account, such as the spread of the virus, vaccine availability and capacity of the health system.
EMA is not involved in national vaccination campaigns.
In each Member State, advisory bodies called national immunisation technical advisory groups (NITAGs) are responsible for providing advice on how the Member State should give vaccinations. These bodies are best placed to take account of local conditions.
EMA is not involved in national vaccination campaigns. Nor is the Agency involved in negotiating potential vaccine availability, funding or deployment at EU or national level after authorisation.
For more information, see:
Each country needs to take its own specific situation into account, such as the spread of the virus, vaccine availability and capacity of the health system. Countries may decide to use the vaccines at their disposal differently.
EMA’s scientific evaluations are the foundation upon which individual EU Member States design and implement their own national vaccination campaigns.
EMA’s evaluations define the benefit-risk balance of each vaccine in the different populations studied. The benefits of all the currently authorised COVID-19 vaccines outweigh the risks when used as described in the product information.
EU Member States can take decisions on which COVID-19 vaccines are included in the EU Digital COVID Certificate and the length of their validity.
Member States can apply broader criteria when accepting COVID-19 vaccines for travel purposes. These can include, for example, World Health Organization (WHO) listed vaccines that have not necessarily undergone the EMA process of authorisation, but that have been approved in other countries.
Decisions on how vaccinations are deployed also fall under the responsibility of each Member State.
For its part, EMA is responsible for the scientific evaluation of vaccines seeking EU marketing authorisation, and monitoring their safety.
Official information on this topic is available in all EU languages at:
The World Health Organization (WHO) has made recommendations for an emergency use listing (EUL) for some COVID-19 vaccines. These are not marketing authorisations, but are designed to support temporary availability and use in emergency situations.
Each WHO Member State can allow the emergency use of a product under an EUL in their country.
However, in the EU, WHO recommendations for EUL cannot replace the centralised authorisation procedure involving a scientific evaluation by EMA.
An EU marketing authorisation offers a robust post-authorisation regulatory framework based on legally binding obligations, safeguards and controls.
For more information, see:
Vaccine safety
The latest safety information on each authorised COVID-19 vaccine can be found on a dedicated web page as well as in monthly safety updates:
These updates give an overview of EMA’s safety committee’s (PRAC) regular evaluation of vaccine safety.
They also provide information on the suspected side effects that individuals and healthcare professionals in the EU reported after using a particular vaccine. PRAC takes these reports into account in its assessments.
For more information, see:
COVID-19 vaccine developers need to submit specific data on their vaccine. EMA then carries out a thorough assessment of these data to reach a scientific opinion on whether the vaccine is safe, efficacious and of good quality, and is therefore suitable to vaccinate people.
Efficacy is measured by looking at how well the vaccine works in clinical settings, for example how well the vaccine prevents symptomatic disease.
For more information on the studies required for approval, see:
The data submitted in a marketing authorisation application for a COVID-19 vaccine must include information on:
COVID-19 vaccines need rapid distribution to billions of people across the world.
This poses a challenge for any company developing a COVID-19 vaccine. It is the same for vaccines made using traditional or new methods.
Some developers decided to start producing COVID-19 vaccines earlier than usual, before their vaccine was authorised. They still had to uphold the same good manufacturing practice (GMP) standards that apply to all vaccine manufacturers in the EU.
COVID-19 Vaccine Safety, Effectiveness, and Other Important Information
Large studies have found that the COVID-19 vaccines are highly effective and safe.
As we learn more about COVID-19 variants, we know that vaccination remains our most effective weapon against this tenacious virus and our best opportunity to end this pandemic.
Mini Kamboj, MSK’s Chief Epidemiologist, answers some frequently asked questions about the COVID-19 vaccines and how they work.
How effective are the COVID-19 vaccines?
The COVID-19 vaccines are among the most effective vaccines in history. They are as effective — if not more — than vaccines for polio, chicken pox, measles, and the flu.
The vaccines all provide strong protection against severe disease, hospitalization, and death from COVID-19.
How do the COVID-19 vaccines work?
The vaccines all work by teaching cells how to make one part of the COVID-19 virus (the spike protein) in order to trigger an immune response. What those instructions look like and how they make their way inside your body is a little bit different depending on which vaccine you get.
In all cases, the vaccine trains your body to recognize the virus so that if you are infected, your immune system is ready to fight it.
Do the COVID-19 vaccines protect against variants?
Research is ongoing. Because the vaccines are extremely effective overall, it has been seen that they are also at least somewhat effective against emerging variants.
Variants are another reason why you should get vaccinated against COVID-19 as soon as you are eligible. The more people are vaccinated, the less chance the virus will have to develop a new mutation.
How long does the vaccine protection last?
No vaccine protects forever against getting the virus or spreading it to others. That’s why it’s very important to continue following safety guidelines, such as social distancing, wearing a mask in some situations, and regularly washing hands.
Are MSK employees required to be vaccinated?
Yes. All MSK employees must be vaccinated against COVID-19 as a condition of their employment. MSK is following the New York State and New Jersey COVID-19 vaccine mandates for healthcare workers.
The COVID-19 vaccines were developed so quickly. How can I be sure that the COVID-19 vaccines are safe?
The COVID-19 vaccines were developed fast because scientists had a head start. The technology already existed and using it to develop a vaccine for a new virus became an international priority, unlocking billions of dollars to ensure safety while moving urgently to save lives. Regulators streamlined some steps in the authorization process, but the vaccines still had to meet the FDA’s rigorous safety and effectiveness standards. The CDC continues to carefully track all adverse reactions.
A few extremely rare instances of severe side effects have emerged and been investigated, but scientists have concluded the risk of getting severely ill from COVID-19 is far greater than the risk of these side effects. Here is proof of this careful and ongoing scrutiny:
There is incorrect information from unreliable sources on social media about how the Pfizer-BioNTech and Moderna vaccines use something called messenger RNA (mRNA). The facts are that there are thousands of different kinds of mRNA in human cells. Each kind of mRNA does different things.
It’s important to know mRNA is not the same as DNA and cannot be combined with DNA to change your genetic code.
Here’s how the mRNA vaccines work: They use a tiny piece of the coronavirus’ genetic code to teach your immune system how to make a protein that will trigger an immune response if you get infected. The mRNA is fragile and it delivers the instructions to your cells to make antibodies against SARS-CoV-2. The mRNA does not enter the nucleus of the cell — the part that contains your DNA.
The vaccines do not cause cancer. They do not expose you to the virus that causes COVID-19. You cannot get COVID-19 or any other infection from the vaccine. Read more about how mRNA vaccines work »
Should people with cancer get the COVID-19 vaccines?
Yes. We strongly recommend that our patients with cancer get the COVID-19 vaccine. Some cancer treatments like chemotherapy or radiation can reduce how well a person’s immune system responds. It’s possible that the COVID-19 vaccines may not be as effective in those patients. Even so, some protection is better than none.
Are COVID-19 vaccines safe for women who are trying to get pregnant, are pregnant, or breastfeeding?
Yes, the vaccines are safe and are recommended for people who are trying to get pregnant, are pregnant, or are breastfeeding. In late September 2021, the CDC issued a strong recommendation for people who are pregnant or are trying to become pregnant to get vaccinated. This is because pregnant people are at higher risk for severe COVID-19 illness and adverse pregnancy outcomes, including preterm birth.
There is no evidence that COVID-19 vaccines cause any problems with pregnancy, including development of the placenta. As of November 29, 2021, more than 177,000 people registered with the CDC have indicated that they were pregnant when they were vaccinated. A group of them are being closely monitored to see how the vaccine affects pregnant people. No safety concerns have emerged.
Research has shown that pregnant people who are vaccinated not only protect themselves but also their babies, by passing on antibodies in their umbilical cord and breast milk.
There is no evidence that the COVID-19 vaccines cause infertility in women or men.
Deborah Goldfrank, Head of General Gynecology at MSK, explains what to know about the safety and effectiveness of the vaccines for people who are pregnant, breast-feeding or planning to have children.
Are the vaccines safe for me if I have already had COVID-19?
The CDC encourages people who have had COVID-19 to get vaccinated. Some of the people in the vaccine studies had evidence of a prior COVID-19 infection. They had side effects from the vaccine that were similar to those who had not been previously infected.
What are the side effects of each vaccine?
The vaccines reported similar side effects, which don’t last long — about one to three days. People receiving the vaccines reported pain at the injection site, fatigue, headache, and muscle pain. Severe adverse reactions are rare.
People with common allergies to medications, foods, inhalants, insects, and latex are no more likely than the general public to have an allergic reaction to the mRNA vaccines, according to guidance from the American College of Allergy, Asthma, and Immunology.
Can I do anything ahead of time to reduce any side effects from the vaccine?
You should wait until after being vaccinated to see how you feel. If you do experience side effects, it is OK to take an over-the-counter drug like Advil or Tylenol to lower a fever, reduce chills, or relieve a headache or body aches.
Side Effects of a COVID-19 Vaccine: Why They Happen and How to Treat Them
Do the COVID-19 vaccines contain animal products?
No, the vaccines do not contain animal products or animal-derived ingredients such as pork, shark squalene, gelatin, cholesterol, egg, or milk. In addition, none of them contain preservatives, gelatin or latex. All COVID-19 vaccines also are free from metals such as iron, nickel, cobalt, lithium, rare earth alloys or any manufactured products such as microelectronics, electrodes, carbon nanotubes, or nanowire semiconductors.
Should I get an antibody test after the COVID-19 vaccine to make sure it’s working?
Antibody testing is not currently recommended to check someone’s immunity to COVID-19 following vaccination. The COVID-19 antibody test used at MSK detects the immune response after being infected by COVID-19; it does not measure the immune response as a result of the vaccine. That’s why it should not be routinely ordered to assess vaccine response.
Что нужно знать о миокардите, редком побочном эффекте вакцины COVID-19 у молодых людей
Кардиолог Мишель Джонсон говорит, что вакцина против COVID-19 крайне редко вызывает проблемы с сердцем. В случае их возникновения они обычно проходят самостоятельно или с помощью лекарств.
Возможно, вы читали о проблемах с сердцем у некоторых людей, получивших вакцину Pfizer-BioNTech COVID-19 (Comirnaty®) или вакцину Moderna COVID-19 (Spikevax™).
Эти редкие побочные эффекты называются миокардит — поражение среднего слоя сердечной мышцы, и перикардит — воспаление оболочки сердца. Люди, испытывающие такие ухудшения состояния здоровья, сообщают об усталости, боли в груди или изменениях в сердцебиении (учащенное биение, стук или пульсация).
Центры контроля и профилактике заболеваний (CDC) впервые сообщили об этих побочных эффектах в июне 2021 года. Сотрудники CDC продолжают отслеживать данные, чтобы лучше понять, когда и почему возникают эти побочные эффекты.
Мишель Джонсон (Michelle Johnson), кардиолог центра Memorial Sloan Kettering Cancer Center, утверждает, что эти проблемы с сердцем возникают очень редко, поддаются лечению и не так опасны, как сам COVID-19.
Молодые мужчины подвержены наибольшему риску, но общий риск очень низок
Молодые мужчины в возрасте от 12 до 39 лет — это группа, у которой наиболее вероятно развитие миокардита или перикардита после введения вакцины против COVID-19. Эти побочные эффекты возникали только у людей, получивших вакцину Pfizer-BioNTech или вакцину Moderna. Обычно они проявлялись после 2-й дозы и в течение недели после вакцинации.
Однако риск для всех, кто получает вакцинацию, очень низок.
«Миокардит или перикардит после вакцины COVID-19 встречаются крайне редко после первичной вакцинации, — говорит д-р Джонсон. — Еще более редки случаи после повторной иммунизации».
Молодые мужчины в возрасте от 12 до 39 лет могут увеличить временной промежуток между получением 1-й и 2-й дозы (первичной серии вакцинации), чтобы снизить риск развития миокардита или перикардита. Между введениями вакцины должно пройти 8 недель.
Людям из других групп следует подождать 3 недели (для тех, кто получил вакцину Pfizer) или 4 недели (для тех, кто получил вакцину Moderna) между получением доз в рамках первичной вакцинации.
Лечение миокардита и перикардита
Если у вас появилась боль в груди или изменилось сердцебиение, звоните по номеру 911.
Большинство людей успешно лечатся от миокардита или перикардита у кардиолога и могут быстро прийти в себя и восстановиться.
«Оба заболевания обычно проходят самостоятельно или требуют медикаментозного лечения, — комментирует д-р Джонсон. — В тяжелых случаях пациенту может потребоваться госпитализация для более агрессивной стратегии лечения — применения внутривенных лекарств, установки устройства, помогающего сердцу перекачивать кровь, или проведения операции».
COVID-19 гораздо опаснее для сердца, чем побочные эффекты от вакцины
«Проблемы с сердцем у людей молодого возраста часто бывают вызваны вирусными инфекциями, такими как COVID-19», — продолжает доктор Джонсон.
«У людей молодого возраста с большей вероятностью возникнет миокардит или перикардит от самого COVID-19, чем от вакцины против COVID-19», — утверждает она.
Вакцины против COVID-19 обеспечивают надежную защиту, предотвращая тяжелое течение заболевания, риск госпитализации и смерти от коронавируса. Серьезные побочные эффекты, в том числе миокардит, перикардит, анафилаксия (тяжелая аллергическая реакция) или синдром тромбоза с тромбоцитопенией (тромбоз на фоне низкого уровня тромбоцитов), возникают очень редко. В центре CDC постоянно наблюдают за этими и всеми другими возможными проблемами.
«Нам известно, что преимущества вакцины намного перевешивают риски»,— говорит доктор Джонсон. «Я и специалисты центра CDC настоятельно рекомендуем каждому человеку пройти вакцинацию и повторную иммунизацию, разумеется, если ему это можно».
В России выросло число госпитализаций и смертей от COVID
За прошедшие сутки количество россиян, госпитализированных с COVID, выросло более чем в два раза и составило 4673 человека, сообщает оперативный штаб. За предыдущие сутки в больницы с диагнозом COVID попали 1988 человек, рост показателя составил 135%.
Выросло также и количество умерших после заражения коронавирусом: если сутки назад оперативный штаб сообщил о 77 летальных исходах, то сегодня — о 94 умерших после заболевания COVID. Это максимальное количество умерших от COVID за сутки с 21 мая.
Всего за сутки в России выявили 37067 новых случаев COVID, выписано в связи с выздоровлением 36729 человек.
Максимальное за последние месяцы количество новых случаев COVID в России за сутки было зафиксировано 27 августа — тогда болезнь диагностировали у 47093 россиян.
Накануне в Роспотребнадзоре сообщили, что доля детей, заразившихся коронавирусом в этом году, выросла до 18% по сравнению с 2020–2021 годами, когда дети, заболевшие COVID, составляли 10–11% от всех заразившихся.
«У детей заболевание чаще всего протекает под маской респираторной инфекции либо в бессимптомной форме. Мы заметили еще один позитивный момент применительно к детям — при «омикроне» пока в нашей клинике не отмечалось ни одного случая мультивоспалительного синдрома, хотя раньше это осложнение отмечалось достаточно часто», — сказал академик РАН, заместитель директора по научной работе ЦНИИ эпидемиологии Роспотребнадзора Александр Горелов.
Однако постковидный синдром, по словам эксперта, встречается у детей так же часто, как и раньше, отметил Горелов. Причем примерно у 30% детей, перенесших COVID-19, некоторые симптомы остаются — в первую очередь слабость, разбитость, рассеянность внимания.
Роспотребнадзор 16 августа посоветовал региональным властям рекомендовать гражданам носить маски, если показатель заболеваемости составляет выше 50 случаев на 100 тыс. населения.
«Эпидемическая ситуация по COVID-19 в России характеризуется продолжающимся ростом числа выявленных случаев. В разрезе регионов страны фиксируются различные темпы прироста. В субъектах Российской Федерации, где уровень недельного показателя заболеваемости превышает 50 случаев на 100 тыс. населения, целесообразно рекомендовать ношение масок в общественных местах, в местах скопления людей, на транспорте и в закрытых помещениях (по месту работы или учебы)», — сообщили тогда в ведомстве.
Ряд регионов России уже последовали этим рекомендациям и вернули масочный режим в общественных местах.
Lancet опубликовал данные о бесполезности массовой ревакцинации от COVID
Массовая ревакцинация от коронавирусной инфекции COVID-19 сейчас не является необходимой, и, напротив, может привести к побочным эффектам. К такому выводу пришла международная группа ученых, среди которых главный научный сотрудник Всемирной организации здравоохранения (ВОЗ) Сумья Сваминатан и исполнительный директор программы ВОЗ по чрезвычайным ситуациям в области здравоохранения Майкл Райан. Их статья опубликована в журнале The Lancet.
По мнению авторов исследования, ранняя ревакцинация от коронавируса может привести к побочным эффектам. Эксперты подчеркивают, что это касается как мРНК-вакцин, так и препаратов на основе аденовируса.
В докладе говорится, что если бустерные дозы будут вводиться в организм слишком рано или слишком часто, то это может вызвать у пациента миокардит (в данном случае речь идет о введении мРНК-вакцин, то есть препаратов от компаний Pfizer и Moderna), а также синдром Гийена-Барре (здесь имеются в виду вакцины на основе аденовируса, включая «Спутник V» и препарат от AstraZeneca).
«Хотя преимущества первичной вакцинации против COVID-19 явно перевешивают риски [заражения коронавирусом], могут возникнуть и иные риски, если бустеры будут широко внедряться слишком рано или слишком часто, особенно с вакцинами, которые могут иметь иммуноопосредованные побочные эффекты», — говорится в статье.
Ученые утверждают, что новая волна COVID-19, вызванная дельта-штаммом, усугубила мировой кризис общественного здравоохранения и заставила правительства большинства государств задуматься о необходимости бустерных доз для вакцинированного населения. «Хотя идея дальнейшего сокращения числа случаев COVID-19 путем повышения иммунитета у вакцинированных людей и привлекательна, любое решение об этом должно основываться на фактических данных и учитывать преимущества и риски для отдельных лиц и общества», — говорят эксперты.
По их словам, заявления о том, что в ближайшее время может потребоваться бустерная вакцинация, если они не будут подтверждены надежными данными и анализом, могут отрицательно повлиять на доверие к вакцинам и подорвать усилия первичной вакцинации. «Если в конечном итоге будут использоваться бустеры, необходимо будет определить конкретные обстоятельства, при которых прямые и косвенные выгоды от этого будут явно полезными. Дополнительные исследования могут помочь определить такие обстоятельства», — отмечают авторы исследования, добавляя, что ревакцинация может понадобиться людям с ослабленным иммунитетом, а также тем, у кого не сформировалась защита после основной вакцинации. Вместе с тем они подчеркивают, что если у человека не сформировался иммунитет после первой прививки, то эффекта от бустера тоже может не возникнуть.
Вакцинация против COVID‑19: вопросы и ответы
Изображение с сайта maxpixel.net
Ситуация с COVID-19 и вакцинацией сложная, много шума и мало простых ответов. Ваш покорный слуга занимается исследованиями адаптивного иммунитета последние десять лет, и, казалось бы, должен в чем-то разбираться. Но и ему, мне то есть, разобраться непросто.
Дмитрий Чудаков, доктор биологических наук, директор Института трансляционной медицины РНИМУ им. Н. И. Пирогова, заведующий отделом геномики адаптивного иммунитета ИБХ РАН, профессор Сколтеха, директор по науке в MiLaboratory
По состоянию на 30 июня 2021 накопились, с одной стороны, циркулирующие в Интернете, головах, и в моей собственной голове, вопросы, а с другой — определенный объем статистической информации, который позволяет примерно сориентироваться. Я постарался структурировать самое важное — скорее для самого себя. Но, возможно, в целом этот (субъективный) взгляд на вещи поможет кому-то лучше разобраться в ситуации и принять верные решения.
Дисклеймер: совсем очевидные вещи и всякие идиотские страшилки про вакцины тут не обсуждаю.
Сформулировал ниже в формате вопросов и ответов интервью у самого себя. Эти ответы не полностью основаны на имеющихся научных и клинических данных, а скорее являются синтезом доступной информации и моего понимания фундаментальной иммунологии с позиций Т- и В-клеточного иммунитета. При этом профессиональным иммунологам, вирусологам, разработчикам вакцин они могут показаться поверхностными, а широкой аудитории — заумными. Не обессудьте, танцую как умею.
1. Каких эффектов мы ждем от вакцин — зачем вакцинироваться?
Мы ждем двух разных эффектов и в разной степени добиваемся обоих.
А. Защита от тяжелого течения заболевания.
Такая защита формируется за счет продукции антител плазматическими клетками (в том числе долгоживущими), формирования В-лимфоцитов памяти (способных произвести новые антитела, а также доточить их напильником в случае прихода новых вариантов эволюционирующего вируса), формирования клонов цитотоксических Т-лимфоцитов (убивают зараженные вирусом клетки) и Т-лимфоцитов хелперов (помогают быстро сформировать Т- и B-клеточный ответ при повторной инфекции). Отчасти также, возможно, за счет долговременной настройки врожденного иммунитета (но это не точно).
В. Защита от инфекции как таковой — т. е. ситуации, когда вирус проник и активно размножается в наших клетках. Позволяет достичь высокого уровня популяционного иммунитета и остановить распространение вируса.
Такая защита, видимо, достигается только высокими титрами нейтрализующих антител (не дают вирусу инфицировать) и высокой концентрацией антиген-специфичных цитотоксических Т-лимфоцитов (сразу убивают немногие зараженные клетки). Поддерживать такие уровни всю жизнь может оказаться сложно, однако в текущей эпидемиологической ситуации целесообразно стремиться к этой цели, с тем чтобы остановить распространение и замедлить эволюцию вируса.
2. Защищают ли аденовирусные вакцины, такие как «Спутник V» или AstraZeneca, от тяжелого течения COVID-19, в том числе варианта «дельта»?
В случае доминирующего сейчас варианта «дельта» — примерно на 90%. То есть вероятность тяжелого течения заболевания снижается примерно в десять раз.
Об этом говорят данные по вакцине AstraZeneca, очень близкой по своему действию к «Спутнику V» [1].
Данные по московским больницам несколько противоречивые, но в целом, видимо, эффект от «Спутника V» сходный.
Защита от факта инфекции, вероятно, несколько выше и продолжительней для мРНК-вакцин — за счет амплитуды В- и Т-клеточного ответа [2]. Однако суть иммунного ответа (пункт 1А) аналогична, и в плане защиты от тяжелого течения аденовирусные вакцины если и уступают, то несущественно.
3. Защищают ли аденовирусные вакцины, такие как «Спутник V» или AstraZeneca, от распространения COVID-19 в популяции, в том числе варианта «дельта»?
Возможно, эффективность аденовирусных вакцин в этом аспекте несколько уступает мРНК-вакцинам, дающим более высокую амплитуду и продолжительность иммунного ответа [2]. Причины описаны в пункте 1В.
Note: это не значит, что мРНК-вакцины лучше. Покажет время. Но они чутка посильнее.
4. Следует ли России закупить мРНК-вакцины и предложить населению?
По многим причинам.
Примерно по тем же причинам следует поддерживать развитие биотеха в стране в целом и развитие мРНК-вакцин в частности. Помимо вирусных инфекций, это также фактически единственный тип вакцин, который сегодня подает надежды в онкологии.
5. Существуют ли способы приобрести долговременный В- и T-клеточный иммунитет к COVID-19?
Например, на определенное время нас, видимо, защитят такие комбинации:
Вывода тут два, хотя он примерно один:
6. Правда ли, что аденовирусная вакцина — «одноразовая»?
Судя по всему, нет, всё больше информации по эффективности бустирующего эффекта («буста») при последующих вакцинациях.
7. Вакцинироваться через шесть месяцев после заболевания в легкой форме — разумно?
Конкретная озвученная где-то цифра в шесть месяцев не имеет четкого статистического обоснования, но таковое мы получим нескоро. Совокупная информация о повторных и даже о двойных повторных заболеваниях, титрах антител, доступности вакцин, целесообразности ревакцинации как таковой, простота восприятия простой цифры — говорят о разумности интервала в шесть месяцев применительно к текущей ситуации.
8. Нужно ли вакцинироваться как можно чаще, например ежемесячно?
Иммунная система в результате уйдет в анергию (откажется перманентно активироваться на одно и то же).
9. Что лучше с точки зрения формирования долговременного иммунитета — переболеть в легкой форме и вакцинироваться или наоборот?
Во-первых, выбирать не приходится, так как без вакцинации высока вероятность переболеть в тяжелой форме или погибнуть.
Во-вторых, вероятно, лучше сначала прививка, так как в этом случае В-клеточный ответ будет сфокусирован на S-белке. А это скорее хорошо. Иммунная система вообще-то сама заранее не знает, антитела против какого вирусного участка окажутся нейтрализующими. И в целом она всегда балансирует, выбирает разные клоны для ответа. Если мы можем указать ей на верную мишень — это правильно. В ходе заболевания в дальнейшем антительный ответ также скорее будет направлен на эту мишень. Это правильный «импринтинг».
10. Для невакцинированного — сопоставимы ли последствия инфекции и вакцинации?
Вероятность смертельного исхода или тяжелых последствий для здоровья в случае инфекции выше на три порядка.
11. Разумно ли отсидеться и не прививаться, пока все вокруг это сделают?
Во-первых, вокруг вас такие же эгоисты (это не ругательство, а свойство человеческой натуры), и, рассуждая так, мы все окажемся одинаковыми дураками (а это уже ругательство, но что делать).
Во-вторых, популяционный иммунитет останавливает распространение только единовременной вакцинацией >80% населения мРНК-вакцинами, как это почти произошло в Израиле (60% вакцинированных). В России это произойдет нескоро, и вы не пересидите.
В-третьих, вирус эволюционирует и будет иногда пробулькивать даже в таких условиях полной вакцинации.
12. Нужно ли вакцинироваться молодым?
Во-первых, плевать на старшее поколение — это бесчеловечно.
Во-вторых, эволюционирующий вирус уже добрался и до молодых в плане тяжелого течения, и этот тренд, весьма вероятно, будет продолжен.
13. Стоит ли опираться на уровень антител?
В плане оценки личной защиты — только косвенно. Наша защита состоит не только из антител, см. пункт 1А. При этом не все детектируемые антитела нейтрализующие, а все тесты разные.
При грамотном мониторинге в динамике можно отследить выраженный подъем уровня антител через месяцы после перенесенной инфекции или вакцинации, что может указывать на бессимптомно перенесенную инфекцию, послужившую естественным «бустом». Однако стандартизовать такой мониторинг и использовать его для принятия решений непросто.
В популяционных исследованиях, оценке эффективности вакцин, степени сформированности популяционного иммунитета — да. При понимании, что снижение титров — это нормально и не означает полную потерю защиты (пункт 1А). Долговременная защита может быть выражена относительно низкими титрами [3] или даже вовсе не детектироваться на уровне антител.
14. В будущем — потребуется ли ежегодно прививаться новыми вакцинами по ходу эволюции вируса?
Возможно — нет, если окажется, что в целом накопленная память В-лимфоцитов способна самостоятельно адаптироваться, а также существуют Т-клетки памяти против консервативных эпитопов, от которых COVID-19 уйти не сможет, и число тяжелых случаев сойдет на нет.
15. Может ли неудачная вакцина привести к более тяжелому течению вирусного заболевания?
Неверный тип вызванного вакциной Т-клеточного ответа (не путать с ADE, риск которого пока никак не подтвердился) может усугубить тяжесть заболевания (см., например, [4]).
Это заведомо не относится к имеющимся аденовирусным («Спутник V», AstraZeneca) и мРНК-вакцинам, для которых:
Однако в целом необходимо с осторожностью относиться к новым типам вакцин, отслеживать индуцируемые типы антиген-специфичного Т-клеточного ответа (Th1/Th2/Th17 etc).
16. Обесценивает ли эволюция вируса наши усилия по вакцинации?
Во-первых, несмотря на математическое снижение эффективности нейтрализации, эти антитела по-прежнему нас защищают.
Во-вторых, В-лимфоциты памяти, кое-как узнающие S-белок предыдущего варианта, быстро дообучатся на новом варианте — они умеют это делать очень хорошо.
В-третьих, вакцинация формирует память Т-лимфоцитов против множества эпитопов S-белка. От них от всех оно быстро не упрыгает.
17. Может ли вакцинация дать импринтинг, при котором ответ на будущие эволюционирующие штаммы COVID-19 будет менее эффективным?
Нет, это крайне маловероятный сценарий.
С приходом новых эволюционирующих волн COVID-19 В-лимфоциты будут дотачивать свои антитела, см. предыдущий пункт.
18. Может ли вакцинация дать импринтинг, при котором ответ на будущие иные коронавирусные инфекции будет ослаблен?
Этот сценарий невозможно полностью исключить, однако он также очень маловероятен.
Сегодня есть текущая задача справиться с имеющейся заразой. И параллельно научиться — к следующей инфекции такого уровня опасности мы подойдем уже с совершенно другим арсеналом защитных инструментов.
Изначально текст был опубликован в «Фейсбуке».
Understanding mRNA COVID-19 Vaccines
What You Need to Know
The Pfizer-BioNTech and Moderna COVID-19 vaccines are messenger RNA vaccines, also called mRNA vaccines. Learn more about Pfizer-BioNTech and Moderna COVID-19 vaccines, including who can get them, doses, and ingredients.
How mRNA COVID-19 Vaccines Work
To trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies. This immune response, which produces antibodies, is what helps protect us from getting sick from that germ in the future.
Facts About mRNA COVID-19 Vaccines
mRNA COVID-19 vaccines cannot give someone COVID-19 or other illnesses.
They do not affect or interact with our DNA.
mRNA COVID-19 Vaccines Have Been Rigorously Evaluated for Safety
mRNA vaccines are safe and effective.
mRNA COVID-19 vaccines have been held to the same rigorous safety and effectiveness standards as all other types of vaccines in the United States. The only COVID-19 vaccines the Food and Drug Administration (FDA) makes available for use in the United States (by approval or emergency use authorization) are those that meet these standards.
mRNA Vaccines Are Newly Available to the Public But Have Been Studied for Decades
Researchers have been studying and working with mRNA vaccines for decades. Interest has grown in these vaccines because they can be developed in a laboratory using readily available materials. This means vaccines can be developed and produced in large quantities faster than with other methods for making vaccines.
mRNA vaccines have been studied before for flu, Zika, rabies, and cytomegalovirus (CMV). As soon as the necessary information about the virus that causes COVID-19 was available, scientists began designing the mRNA instructions for cells to build the unique spike protein into an mRNA vaccine.
Future mRNA vaccine technology may allow for one vaccine to provide protection against multiple diseases, thus decreasing the number of shots needed for protection against common vaccine-preventable diseases.
Beyond vaccines, cancer research has used mRNA to trigger the immune system to target specific cancer cells.
Use CDC’s COVID-19 booster tool to learn if and when you can get boosters to stay up to date with your COVID-19 vaccines. Staying up to date means getting all recommended COVID-19 vaccines including boosters when eligible.
People who are moderately or severely immunocompromised have specific COVID-19 vaccine recommendations, which include a third dose to complete their primary series, as well as two booster doses for those eligible.
Ways Health Departments Can Help Increase COVID-19 Vaccinations
Find strategies and resources for health departments and community leaders to use when planning and implementing activities to generate demand for COVID-19 vaccinations. These include guidance for building COVID-19 vaccine demand in different settings and tips for how to build trust, address misinformation, and tailor messages and materials.
Increasing COVID-19 vaccinations requires easily accessible vaccines and meeting people where they are with compelling information from trusted sources. Below are best practices to consider implementing to help increase COVID-19 vaccinations where people live, work, learn, pray, play, and gather.
Strategy in Action: Multnomah County, Oregon Emergency Operations Center partnered with Medical Reserve Corps volunteers and paramedics to vaccinate 1,400 people who were homebound, providing a sense of freedom to older adults and people with disabilities who had been in lockdown for more than a year.
Encourage employers to help employees get vaccinated. Options include allowing employees to be away during work hours or to take paid leave to get vaccinated, reimbursing employees for transportation costs, and offering on-site vaccination. Remind employees that they are entitled to a COVID-19 vaccine regardless of their immigration or health insurance status.
Strategy in Action: Rising Ground, a New York City-based human services nonprofit, has implemented a variety of COVID-19 vaccine outreach strategies to its employees, including frequent educational workshops on vaccine safety and efficacy, social media campaigns, paid time off to get vaccinated and in case employees they have side effects after vaccination, and on-site vaccinations.
Strategy in Action: The Greater Miami Chamber of Commerce held virtual Trustee Luncheons using Zoom panel discussions with local leaders, physicians, and businesses about COVID-19 and vaccine distribution. This engaging forum enabled participants to share pertinent information and ideas in an approachable and timely way.
Strategy in Action: Merced County Department of Public Health in California partnered with poultry producer Foster Farms and Save Mart Pharmacy to vaccinate 1,000 essential workers. Since September 2020, 370 Foster Farms plant employees tested positive for COVID-19 and nine lost their lives due to COVID-19, making vaccinations a top priority to prevent subsequent outbreaks.
Strategy in Action: The Seattle and King County Department of Public Health developed a flyer tailored to students ages 12–17 years that includes vaccination site information, how to prepare for your vaccine appointment, and frequently asked questions. This flyer is available in 22 languages for schools to distribute to students and parents through their communication channels.
Strategy in Action: New York City is holding school-located mobile vaccination sites for children and is hosting community conversations with parents, teachers, and students. Organizers started with four schools in the Bronx, which had high numbers of COVID-19 cases and low vaccination rates. The city is adding school sites in Manhattan, Queens, and Brooklyn and establishing sites at schools across the city. This effort, in partnership with the city health department and the United Federation of Teachers union, launched in coordination with the city’s “Youth Vax Week.”
Strategy in Action: In Jacksonville, Florida, Black and African American populations were lagging far behind White populations in vaccinations. In response, the health department partnered with Black and African American churches in areas with low vaccination rates to hold on-site vaccination clinics, which vaccinated 60,000 people.
Strategy in Action: Connecticut and California held mobile vaccination clinics throughout the summer at amusement parks and beaches on a walk-up, no-appointment basis.
Strategy in Action: Many YMCAs are offering free drop-in childcare for parents while they get vaccinated. YMCAs also provide communities with vaccine information. Some serve as vaccination centers and partner with public and private entities, including state and local health departments, local pharmacies, and Lyft, to help people get vaccinated.
Strategy in Action: The City of Lubbock Health Department (CLHD) partnered with its public transportation provider, Citibus, to hold mobile vaccination clinics at existing local events, offering COVID-19 vaccines and information to event goers. Events included a local school board festival, back-to-school events, a Juneteenth celebration, art fairs, a Fall Fiesta celebration, and local church events. As of August 2021, CLHD used the Citibus mobile vaccination clinics at 29 events and administered 1,400 vaccines.
For help with how to partner with community groups, refer toCDC’s Guide for Community Partners.
Strategy in Action: The Mental Health Association (MHA) of Essex and Morris Counties in New Jersey serves 10,000 people annually, including 1,000 patients with severe and persistent mental illness. MHA informed its patients about COVID-19 vaccines through conversations, virtual education sessions, and tailored educational materials. MHA also coordinated with its county governments to host five vaccination clinics, vaccinating clients, staff, and community members.
COVID-19 fact sheets are available in more than 30 languages from the National Resource Center for Refugees, Immigrants, and Migrants
Strategy in Action: Feeding America and the Blue Cross Blue Shield Association created a Vaccine Awareness Toolkit in English and Spanish for food bank staff and visitors, providing COVID-19 vaccine information from the CDC and other medical experts. They also offer customizable resources for Feeding America food banks to access on the HungerNet SharePoint site (login ID and password required).
This is an opportunity for community members to have conversations about the vaccines in a familiar environment with people they trust. Having a safe space to get their vaccine questions answered and hearing consistent vaccine information from multiple sources may help increase community members’ vaccine confidence.
Strategy in Action: The Sacramento Lesbian, Gay, Bisexual, Transgender (LGBT) Community Center offers COVID-19 vaccination and testing together with other services such as flu shots, HIV testing, and STI testing. These services are delivered onsite and at mobile clinics throughout the city and at events.
Connecting with your communities virtually through trusted messengers is essential to sharing timely information about COVID-19 vaccines and vaccination sites, answering questions, and addressing misinformation. Below are best practices to consider when planning and implementing COVID-19 vaccine online outreach activities tailored to your communities.
Strategy in Action: The National Association of Community Health Centers uses its Twitter page to promote its selfie signs and other social media resources .
Strategy in Action: New York City Health System partnered with Coney Island Hospital on a social media campaign, #NYCYouthVaxWeek, to combat misinformation about the COVID-19 vaccine and encourage parents to get their children vaccinated. The Twitter post links to in-depth vaccine information, including where and how to get vaccinated.
Strategy in Action: Michigan Department of Health and Human Services launched a Twitter campaign #MIdoseofhope with videos of residents throughout the state sharing why they got vaccinated—from a woman who lost her mother to COVID-19 to teens who want to go to school dances. The videos are in black and white, are closed captioned, and provide information on how to get vaccinated.
Strategy in Action: The Chicago Department of Public Health posts upcoming pop-up vaccination locations on Twitter with colorful images and pertinent information, including date, time, location, address, and types of vaccines available.
Strategy in Action: Pima County Health Department in Arizona incentivized youth to create short videos on social media (TikTok, Instagram, YouTube, and Facebook) through the #VaxTruthChallenge to tell their COVID-19 vaccine stories. The challenge was open to 12- to 24-year-olds and promoted through youth organizations, schools, clubs, and mobile vaccination sites. The goal was to create an opportunity for youth to encourage other youth to get vaccinated through social media.
Strategy in Action: Mariposa County Health and Human Services Agency in California hosts monthly Facebook live events led by trusted community physicians who can answer participants’ COVID-19 questions. The county also posts on its website pre-recorded “Talk with the Doc” videos to provide county-specific COVID-19 updates and information. The Los Angeles County Department of Public Health hosted a live Vaccine Town Hall for Parents ahead of the 2021-2022 school year. Public health and medical professionals provided information about COVID-19 protocols in schools and answered parents’ COVID-19-related questions
Strategy in Action: The Cornell Farmworker Program and Finger Lakes Community Health in New York State jointly sponsored a question-and-answer webinar about COVID-19 vaccines in English and Spanish.
Strategy in Action: The Detroit Health Department held a live Vaccine Confidence Town Hall conversation via Zoom for individuals with disabilities, which included an ASL interpreter and closed captions.
To help increase demand for COVID-19 vaccinations, it’s critical for health departments to secure their community’s trust. As a health department leader, you can achieve this by fostering strong partnerships with organizations trusted by community members and being responsive to people’s concerns.
Engaging trusted community messengers is a key strategy for building confidence in COVID-19 vaccines. You may need to engage new types of community organizations that you had not worked with before the pandemic. Here are some tips for engaging new partners:
In addition to fostering community partnerships, you can build trust through responsive communication. Below are some tips:
«Спутник V» и не только: сказ об аденовирусных вакцинах
Иммунизации боятся многие, что неминуемо снижает и ценность внедрения новых вакцин. Стоит ли бояться вакцин на основе аденовирусной платформы и есть ли факты, говорящие об их безопасности? Да и что это, собственно, за аденовирусы такие? Рассказываем об этом в нашей статье. Иллюстрация в высоком разрешении.
Автор
Редакторы
Гонки за созданием эффективных вакцин совсем недавно задали новый тренд в фармацевтике, что на наших глазах подстегнуло и всю медицину. Озабоченные поиском скорейшего решения, ученые вспомнили о «старенькой» технологии аденовирусных векторов, ровеснице самой генной терапии (спецпроект о которой вы сейчас продолжаете читать). На основе этой платформы хорошо показала себя вакцина против вируса Эбола, что позволило, немного модифицировав её технологию, оперативно создать и вывести на рынок несколько вакцин против коронавируса — «Спутник V», а также продукты компаний Johnson & Johnson и AstraZeneca. Вакцина «Спутник V», хотя так и не получила одобрения ВОЗ и ЕС, — безусловный прорыв в российской фармацевтике. Рассмотрим в статье, почему аденовирусы стали такой удачной платформой, и какие у них перспективы в создании новых вакцин и не только.
Генная и клеточная терапии
Спецпроект о генной и клеточной терапиях, тернистом пути их развития, первых успехах и надеждах, а также о сложностях регулирования, производства и изучения этих новейших методов лечения.
Партнер спецпроекта — Департамент разработки генотерапевтических препаратов одной из крупнейших российских биотехнологических компаний — BIOCAD. BIOCAD заслужил серьезные позиции на мировом фармацевтическом рынке благодаря выпуску лекарственных препаратов на основе антител.
Дисклеймер
Эта статья в основном о применении аденовирусов в составе вакцин, ведь пандемия новой коронавирусной инфекции сделала именно эту область крайне актуальной. Мы почти не будем касаться попыток системной генной терапии такими носителями (пока серьезными успехами не увенчавшихся), а также их широкого использования в научных исследованиях.
Новое начало
Пандемия коронавируса в одночасье изменила привычные устои и правила поведения людей всего мира [1], [2], что вместе с нарастающей нагрузкой на здравоохранение и пугающей статистикой смертности запустило массированные исследования и разработки препаратов, способных остановить COVID-19. Время это определенно было не лучшим, но именно здесь в медицине и фармацевтике возник какой-то новый импульс. Ученые со всего мира пытались найти решение новой и острой проблемы, что, очевидно, подстегнуло и всю науку. Насколько именно подстегнуло — сказать пока трудно. Как минимум, мы уже получили новые лекарства [3], и даже одна новая терапевтическая модальность вышла из многолетней тени клинических исследований к регистрации и практике использования у людей. В будущем не исключено, что появятся и другие инновации, начало которых было заложено именно в этом напряженном поиске спасения от новой инфекции. Ведь в истории так много примеров, когда острая потребность в чем-либо рождала знания, а уже это выводило на новый уровень технологии, и даже могло увлечь за собой весь мировой прогресс.
Сейчас ковид уже не так свирепствует, что во многом связано с доминированием варианта Омикрон, ранее называемого даже «живой вакциной». Учитывая высокую смертность, такая его характеристика вряд ли уместна, но доля правды в ней есть. Данный тип распространялся среди населения с фантастической скоростью и оказался менее опасен, чем предыдущий «доминатор» Дельта. Это, вместе с усиленной вакцинацией, всё же привело к некому подобию коллективного иммунитета. Есть соображения, что дальше — больше, и вскоре новая коронавирусная инфекция достигнет эндемически устойчивого состояния. Это значит, что число инфицированных экспоненциально увеличиваться уже не будет, но напротив — станет предсказуемым. Смертность от этого, конечно, никуда не уйдет, но бремя заболевания сравнится с другими известными и опасными инфекциями, такими как грипп. Это позволит избежать серьезных ограничений, от которых во время предыдущих волн пандемии все так сильно страдали. Сценарий этот пока не гарантирован, ведь на его развитие влияют множество неизвестных. Это и появление новых вариантов, и продолжительность существующего иммунитета (пока точно не установленная), и недоверие к вакцинам, неспроста включенное в список глобальных угроз здоровью населения [4] (что было сделано задолго до наступления коронавирусной эры). Так или иначе, пока что COVID-19 с нами, и необходимость вакцинации против него актуальна.
В этой статье попробуем разобраться, насколько эффективны и безопасны современные аденовирусные вакцины от COVID-19: «Спутник V» и ему подобные. А заодно поговорим и о других препаратах на основе этой платформы. Выясним, что представляют собой сами векторные аденовирусы, в чем их особенность и уникальность. И почему вакцина против нового коронавируса на их основе была одобрена к применению раньше других.
Векторы — это как раз и есть генетически модифицированные вирусные частицы-носители для доставки лечебных генов в клетки человека. Они бывают как аденовирусными, так и основанными на других диких вирусах: лентивирусах [5], ретровирусах, аденоассоциированных вирусах [6] и так далее. В подробностях, чем эти носители различаются и как всё это работает, рассказывает статья «Генная терапия: познакомьтесь с лекарствами будущего» [7] и другие публикации нашего цикла о генной и клеточной терапиях.
Что было раньше?
Ученые начали тестировать первые аденовирусные векторы (рис. 1) в далеких 1980-х, когда создавали неспособные к размножению вирусы, фокусируясь в основном на серотипе 5 (Ad5). Эти исследования подогревались надеждой, что данный вектор станет для генной терапии прорывом, на что немного намекал предшествующий опыт: аденовирусы уже неплохо показывали себя в испытаниях на животных. А в США еще за тридцать лет до создания первых векторов начали применять вакцины на основе живых (!) аденовирусов серотипов 4 и 7. Их тогда давали новобранцам в армии для профилактики респираторных заболеваний, и, что интересно, такое их применение востребовано до сих пор.
Рисунок 1. Структура аденовирусов: внутри частицы линейная двухцепочечная ДНК длиной от 26 до 45 килобаз (тысяч пар нуклеотидных оснований). Снаружи белковая оболочка (капсид) — многогранник типа икосаэдра со скругленными ребрами, размером приблизительно 100 нанометров [8]. На её поверхности основные структурные белки: гексон, пентон и вырастающий из него «волокнистый» белок. На конце последнего — белковый «набалдашник» (шарообразный домен), связывающийся с клеточным рецептором при проникновении вируса в клетку.
Со временем исследования подвели к идее использования аденовирусных вакцин против ряда опасных возбудителей, таких как вирусы герпеса и лихорадки Эбола, флавовирус, вирус Зика, респираторно-синцитиальный вирус человека и возбудитель малярии. Отдельного упоминания заслуживает вакцина на платформе Ad5 против вируса иммунодефицита человека (ВИЧ). Попытки её применения были весьма многообещающими, но по итогу полностью провалились [9]. Как ни странно, выяснилось, что она может даже повышать риски заражения! И хотя точная причина этого неизвестна, предполагается, что «знакомство» иммунных клеток с вектором Ad5 снижает их эффективность в борьбе с возбудителем ВИЧ [10], [11].
Но в истории был и еще один примечательный эпизод, связанный с 5 серотипом аденовируса, всерьез поставивший под сомнение саму возможность генной терапии [12].
Начали не за здравие
Подробнее об этом случае, а также глобально: о фармацевтической индустрии, появлении новых и самых перспективных терапевтических модальностей узнаете из статьи «Три поколения лекарств» [13].
А ведь уже было известно: большие дозы векторов могут быть опасны. В опытах обезьяны, на которых испытывали Ad5, умерли от нарушения свертываемости крови, сопровождавшегося тяжелым воспалением печени. Причем все они получили исключительно высокую дозу аденовирусного вектора [14], [15].
Последствия
В том самом исследовании помимо Гелсингера принимали участие и другие пациенты. Некоторые из них без серьезных последствий перенесли такие же высокие дозы аденовируса, как и он. И точная причина, почему реакция Джесси столь разительно отличалась, до конца до сих пор не установлена. Основная гипотеза связана с активацией врожденного иммунного ответа на вектор, что вызвало системное воспаление со всеми вытекающими последствиями. При этом более сильный врожденный иммунитет мог быть заложен у пациента, например, генетически. Или же предварительное «знакомство» с аденовирусом при естественном инфицировании настолько сильно увеличило иммунный ответ на него при повторной «встрече». Так или иначе, все эти предположения появлялись уже постфактум, в том числе и на основе предпринятых дополнительных экспериментов на животных [15]. А значит, на момент начала исследования опыта и знаний было еще недостаточно, и ученые действовали без четкого понимания возможных последствий. Кажется, что описанный случай будто предостерегает нас: не надо играть с огнем, генная терапия небезопасна! Но давайте разбираться: может ли история Гелсингера служить уроком, и стоит ли бояться аденовирусов в принципе?
Опасности мнимые и настоящие
С аденовирусами человечество взаимодействует на протяжении всей своей истории — они вызывают в том числе и обычную простуду, которая всем так хорошо известна. Вроде бы уже здесь можно слегка расслабиться — простуды пока еще никто не пугался. Ну а рекомбинантные векторы это даже и не вирусы: их дополнительно «обезвреживают», удаляя ответственные за размножение гены и вставляя вместо них гены чужеродных белков-антигенов опасного патогена. Как бы страшно всё это ни звучало, сильно беспокоиться не стоит и здесь. Антиген — это обычно белок оболочки инфекционного агента — сам по себе размножиться и нанести вред организму никак не сможет. А вот «причинить пользу» в случае иммунизации им — да!
И хотя случай Джесси Гелсингера в плохом смысле беспрецедентен, с современной вакцинацией аденовирусными векторами он имеет мало общего. Этому пациенту векторы вводили в системный кровоток, откуда они вполне закономерно распределялись во все органы и ткани. Учитывая количество аденовирусных частиц и их высокую иммуногенность (которая тогда была не вполне изучена), трагические последствия не так и удивительны.
В случае же вакцинации вектор вводится чаще внутримышечно и в организме распределяется более локально. Да и количество вирусных частиц здесь намного меньше. Для «Спутника V», например, это 10 11 на дозу согласно инструкции, то есть — 100 миллиардов векторов в одном уколе. В сравнимых аналогах этой вакцины — западных AstraZeneca и Johnson & Johnson — количество частиц и того меньше: 50 миллиардов в дозе (5×10 10 ) [3]. И хоть числа эти не кажутся маленькими, следует помнить, что клеток в нашем организме на порядки больше: около 30 триллионов (30×10 12 ). А это означает, что заражаемых этими вакцинами клеток будет немного. «Спутник V» при введении дозы заразит максимум одну клетку из 300 (0,3%) [16]. А AstraZeneca и Johnson & Johnson еще меньше: одну из 600 (0,2%). И эффект от этого поначалу будет местным — системным его сделает иммунная система.
Бояться не стоит
Какие последствия может повлечь применение даже самого массового анальгетика, читайте в статье «Биомолекулы» «В чем сила, парацетамол?» [17].
Поэтому, чтобы повысить безопасность и эффективность, исследователям приходится выяснять детали «приключений» лекарственных молекул в каждом конкретном случае: изучать их фармакокинетику [18]. Касается это большинства лекарств, но не вакцин, для которых такие исследования малополезны и обычно не проводятся. Это связано с тем, что дозы здесь слишком малы, и как они там распределяются, всерьез на их эффективность не влияет. Зато биораспределение компонентов вакцин может повлиять на их токсичность, в связи с чем регуляторы выдвигают требования тестировать его на животных, чтобы выявить все побочные реакции и последствия [19], [20].
Куда же распределяются вирусы?
Данные доклинических исследований векторов серотипов Ad5 и Ad26 показали похожую картину биораспределения. После инъекции аденовирусные частицы в основном остаются в месте введения, ограниченно попадая только в печень (Ad5) [21], лимфатические узлы и селезенку (Ad5 и Ad26) [21], [22]. Это согласуется с гипотезой о том, что векторы сами по себе не распределяются (или почти не распределяются), а перемещаются по телу вместе с зараженными клетками [21].
И хотя попадание в органы (особенно в печень) потенциально может нанести вред, ничего подобного в исследованиях на животных обнаружено не было (только обычные обратимые легкие местные и системные реакции). Дело в том, что процессы в организме после введения вакцины не так сильно отличаются от выработки иммунитета при инфицировании природными патогенами, а это зачастую бывает довольно «не сладко». Но именно в этом вся суть иммунизации: «провокация» естественных защитных сил организма приводит их в полную боевую готовность, что и вызывает похожие на заболевание симптомы. Нужные механизмы по умолчанию «вшиты» в каждого из нас.
Иммунитет и вакцина
Задача любой вакцины — ознакомить иммунные клетки с антигеном, заставив «поверить» в наличие патогена, чтобы выработать на него защитный иммунный ответ. Это позволит организму немного потренироваться, чтобы в случае настоящей инфекции быть во всеоружии. При вакцинации — например, «Спутником V» — зараженные аденовирусным вектором клетки начинают производить шиповидный белок (S-белок) оболочки коронавируса, который в этом случае антигеном и будет.
Попадая в организм (рис. 2), аденовирус запускает обе ветви клеточной обороны: врожденный и приобретенный (адаптивный) иммунитет [23]. Его оболочка дополнительно усилит иммунный ответ, работая как адъювант. Это означает, что еще до запуска адаптивного иммунного ответа вектор активирует иммунитет врожденный. И для этого не требуется размножение вируса или экспрессия его генов.
Рисунок 2. Классический путь проникновения аденовирусов в клетку.(1) Белковый «набалдашник» на конце «волокнистого» белка аденовируса связывается с белком CAR на поверхности клетки. Далее вирусный белок пентон своим мотивом RGD взаимодействует с клеточными рецепторами-интегринами, что отчасти разбирает капсид вируса, отщепляя «волокнистые» белки. (2) Рецепторы-интегрины на поверхности клетки запускают эндоцитоз вируса в клетку. (3) Литическая активность белка pVI (находятся под каждым белком-гексоном) способствует высвобождению капсида из эндосомы — мембранного пузырька, в котором вектор перемещается внутрь клетки. (4) Частично разобранные капсиды перемещаются к ядру по «дорогам»-микротрубочкам, подбираясь к комплексу ядерной поры. (5) Вирусная ДНК проникает в ядро, и начинается экспрессия внедренного в вектор целевого гена.
Аденовирус — адъювант
На аденовирусе есть множество молекулярных паттернов (известных как PAMP), помогающих иммунным клеткам узнать в нем «чужака». При приближении вируса к клетке её специальные патоген-распознающие рецепторы опознают эти PAMP (рис. 3), что активирует уже внутри клетки сигнальные пути, «оповещающие» о необходимости сложного и многостороннего иммунного ответа [24]. Он реализуется через включение генов, кодирующих определенные иммунные и воспалительные молекулы, биосинтез которых и усилит защиту от патогена.
Рисунок 3. Врожденный иммунный ответ запускается при активации патоген-распознающих рецепторов клетки молекулярными паттернами вируса (PAMP). Главные «распознаватели» вируса — белок CAR, рецепторы-интегрины, а также Toll-подобные рецепторы (TLR2–4, 7 и 9) [25]. Последние присутствуют не только на поверхности клеток, но и на эндосомах. Так или иначе, распознавание вирусных РАМР-паттернов приводит к запуску множества сигнальных каскадов (cGAS/STING, MyD88- и TRIF-зависимые TLR сигнальные пути), доносящих до ядра клетки информацию о необходимости активации антивирусных генов и биосинтеза белков иммунитета.
Апоптоз — это процесс клеточного самоуничтожения, помогающий регулировать численность и постоянство клеточных популяций, а также играющий важную роль в управляемом развитии организма. На «Биомолекуле» есть про это отдельная статья: «Апоптоз, или Путь самурая» [27].
Усиление иммунного ответа происходит и за счет созревания под воздействием воспалительных цитокинов дендритных иммунных клеток. Эти клетки известны своей отростчатой формой и умением «профессионально» представлять другим иммунным клеткам частицы-антигены. Последнее активирует основные ветви клеточной обороны организма, связывая врожденные и приобретенные иммунные ответы.
Как это работает?
Укол аденовекторной вакцины в мышцы приводит к локальному распределению вирусных частиц в месте инъекции (рис. 4). Они активно проникают в находящиеся там миоциты (мышечные клетки), клетки соединительной ткани — фибробласты — и выстилающие внутреннюю поверхность сосудов клетки-эндотелиоциты, а еще в особые антигенпрезентирующие клетки. К последним как раз относят дендритные клетки, заточенные на поглощение и переваривание бактерий, клеток и других частиц макрофаги и в меньшей степени B-клетки (ответственные также за производство антител). Поглощение чужеродных частиц и демонстрация их элементов на клеточной поверхности позволяет организму выработать на них иммунную реакцию, чтобы затем уже уничтожить несущих такие чужеродные белки-антигены «врагов». Тут-то на первый план дендритные клетки и выходят. Подвергаясь действию цитокинов, они начинают антиген синтезировать и выставлять его на свою поверхность. При этом сами они мигрируют в лимфатические узлы, и уже там обучают ни разу не сталкивавшихся с антигеном «бойцов иммунного фронта».
А это наивные B- и T-клетки, которые «узнают» здесь про антиген, что потом позволяет им «вычислять чужаков». Получив эти «знания», они начинают патрулировать организм в поисках «врага», и, узнавая его, активируют иммунитет. Чтобы вот так обучиться и стать основой «личного состава» оборонительных сил организма, эти живые бойцы проходят, можно сказать, «индивидуальную программу развития». Например, B-клетки перерождаются в плазматические клетки и вырабатывают антитела для связывания и уничтожения патогена. Ну а CD8+ Т-клетки, узнавая фрагмент патогена, обучаются уничтожать его напрямую. При этом и B- и T-клетки способны стать иммунными клетками памяти: можно сказать, «накрепко запомнить» столкновение с антигеном. При реальном инфицировании это поможет быстро узнать «врага» и выработать на него защитную реакцию как раз за счет антител и «убийства» CD8+ Т-клетками.
Рисунок 4. Судьба чужеродного белка-антигена в организме после введения аденовирусной вакцины в мышцы.(1)Прямая презентация: аденовирусная вакцина инфицирует находящиеся в месте инъекции антигенпрезентирующие клетки (АПК). Они синтезируют антиген и мигрируют в лимфоузлы, где презентируют его Т-клеткам. (2)Кросс-презентация: АПК фагоцитируют (поглощают) другие находящиеся в месте инъекции инфицированные аденовирусным вектором клетки, получая вместе с ними и антиген. Затем точно так же перемещаются в лимфатические узлы и демонстрируют там антиген наивным B- и T-клеткам. (3)Кроссдрессинг: еще незнакомая с антигеном АПК «откусывает» находящийся на поверхности другой такой же (только уже инфицированной) клетки антиген — этот процесс известен как трогоцитоз. Далее всё «как по накатанной» — перемещение в лимфоузлы для представления антигена Т-клеткам. (4)Локальная презентация: АПК могут презентировать антиген Т-клеткам и в месте инъекции; ведь с одной стороны некоторое количество последних там уже присутствует — это так называемые резидентные Т-клетки; а с другой — они также будут мигрировать туда, привлекаемые выделяющимися в процессе воспаления цитокинами. (5)Презентация антигена Т-клеткам по месту инъекции возможна не только профессиональными антигенпрезентирующими клетками, но и непрофессиональными. К последним относят все имеющие ядро клетки организма (на рисунке в качестве примера показаны мышечные клетки), но как ясно из названия — они менее эффективно поглощают и представляют антиген.
Путь к иммунной защите
Здесь может возникнуть вопрос: а не слишком ли много инфицированных аденовирусом клеток умрет из-за атаки на них CD8+ клеток? Не будет ли это опасно? Путь попадания вектора ведь отличается от естественного проникновения вируса. Как с этим справляется организм? Тут надо, прежде всего, понять что значит «много», и что иметь в виду под опасностью. Пока что никто специально не считал, сколько уничтожается клеток после инъекции аденовирусной вакцины, но, очевидно, что их будет не больше заражаемых вектором. А на деле даже меньше приведенных выше максимальных цифр в 0,2–0,3%. Это связано с тем, что из-за множества рецепторов для связывания аденовирусов на одной клетке, заразить её смогут одновременно несколько таких частиц. Кроме того, часть векторов еще нейтрализуется специфичными к их белковой оболочке антителами, что также уменьшит их число. Но даже если считать, что одну клетку заразит лишь один вектор, общее количество «инфицированных» не превысит числа клеток, ежедневно погибающих при естественном самообновлении организма. Ведь только при апоптозе ежедневно погибает 10 10 –10 11 клеток. Это число примерно соответствует количеству вводимых в одной дозе вакцины векторов. Но дело тут даже не в количестве, а в механизме происходящего после вакцинации. В устройстве организма, который не только умеет удалять из себя всё лишнее, но и восстанавливаться.
При вакцинации повреждение в месте инъекции провоцирует клеточный стресс, что вместе с адъювантными свойствами векторов вызывает локальное воспаление. Это активирует иммунную систему, привлекая не только «клеточных убийц», но и «санитаров леса» (таких как макрофаги), устраняющих остатки погибших клеток. Очистка от ненужного помогает поддерживать постоянство внутренней среды — тканевый гомеостаз. Дефектные (здесь читай зараженные) клетки из организма будут удаляться. Ну а на их место заступят «новобранцы» из числа клеток-предшественников — резерва, который в организме всегда имеется. (Причем как раз-таки для таких случаев — необходимости замещения поврежденных или инфицированных клеток.)
И всё это абсолютно естественные процессы, и без того постоянно протекающие в организме. В случае же иммунизации они помогают вывести из организма вакцину, оставив после неё лишь клетки памяти и антитела к антигену (для готовности к будущим встречам с «врагом»). Причем постепенно из организма «выйдут» как вирусные частицы, так и зараженные ими клетки, чему активно поспособствуют как CD8+ клетки, так и макрофаги. Как показали исследования на животных, при внутримышечной инъекции аденовирусов в дозах порядка 10 11 вирусных частиц, большая их часть выводится из организма уже через девять дней. Ну а через три месяца в большинстве случаев векторы и вовсе обнаружить в организме не удается [21].
Эти данные получены на кроликах, достаточно крупный размер которых позволяет вводить большую дозу векторов и экстраполировать результаты на человека. Данные же клинических исследований подтверждают, что у людей происходит примерно то же самое [21]. В основном это обычные и вполне ожидаемые при введении вакцин симптомы, такие как лихорадка, усталость и мышечная боль (это показатель иммунного ответа и воспаления, которые проходят сами собой). И хоть ощущения при этом не из приятных, зато мы понимаем, что иммунитет здесь «сработал», и испытывающий эти симптомы, скорее всего, окажется под его защитой. Ну а безопасность применения доказывается как в клинических, так и в пострегистрационных исследованиях таких лекарств.
Три поколения аденовирусных векторов
Ради продвижения вперед и создания нового ученые порою готовы пойти на многое. Это верно и в отношении аденовирусных векторов, для которых исследователи вот уже четыре десятилетия улучшают безопасность и эффективность, подарив нам три поколения таких частиц (рис. 5) [28].
Рисунок 5. Получение аденовирусных векторов.а — Целевой ген помещают во вспомогательный вектор, который содержит также последовательности 5′-ITR, упаковочный сигнал и участок для гомологичной рекомбинации. Затем вспомогательный и основной вектор линеаризируют («распрямляют») и заражают ими клетки HEK-293, в которых между ними происходит рекомбинация генов. Результат этого — векторы первого поколения. б — В рекомбинации между вспомогательным и основным вектором могут также помочь клеточные линии HEK293 CRE, которые производят фермент Cre-рекомбиназу. Здесь в оба вектора (вспомогательный и основной) помимо перечисленного нужно «впихнуть» еще последовательность LoxP; а затем уже заразить ими HEK293 CRE. После рекомбинации можно получить векторы первого или второго поколений. в — Другой вариант — «впихнуть» во вспомогательный вектор не LoxP, а дающую устойчивость к канамицину бактериальную последовательность (а в основной вектор — последовательность устойчивости к ампициллину), после чего заразить ими кишечные палочки штамма BJ5183, и вырастить их на среде с этими антибиотиками. Это поможет отобрать те частицы, в которых рекомбинация состоялась. После этого получившиеся векторы выделяют из бактерий, линеаризируют и заражают ими HEK-293 для получения требуемых количеств вирусных частиц. г — Третье поколение векторов получают внедрением целевого гена в вектор переноса, содержащий только ITR и упаковочный сигнал. Здесь используют также вирусы-помощники, несущие недостающие в векторе переноса гены. Этими двумя частицами заражают модифицированные HEK-293, в которых в конечные вирионы (векторы третьего поколения) упаковываются только последовательности из вектора переноса.
Для адаптации к генной терапии геном аденовируса подвергли множеству изменений. Например, удалили из него гены E1 и E3, что позволило создать векторы первого поколения. Эти частицы уже не размножаются, не провоцируют онкогенез и могут доставить в клетку ген размером до 8 килобаз. Помимо этого, они сильно иммуногенны, слабо и прерывисто синтезируют собственные белки, а также могут «перерождаться» в способные к размножению вирусы. Чтобы обойти все эти минусы, из них стали удалять гены и дальше. Вслед за E1 и E3 «в топку» пошли E2A, E2B и E4, дав векторы второго поколения. Но и они оказались не очень удачными: сложные в производстве, они по-прежнему синтезировали вирусные белки, да еще и теряли внедренный в них ген. Так что пришлось работать дальше.
В векторах третьего поколения удалили уже вообще все вирусные гены, кроме пси-последовательности (известной также как упаковочный сигнал), и обрамляющих внедренный ген инвертированных терминальных повторов (ITR). Эти частицы вызвали больший резонанс: будучи вполне безопасными и менее иммуногенными, они могут нести гены размером уже до 37 килобаз и длительно их экспрессировать.
И каков же итог?
Инженерия аденовируса сыграла решающую роль в разработке препаратов с этими носителями, но именно в вакцинах она востребована в меньшей мере. Дело в том, что снижение иммуногенности, над которым все так долго бились, здесь в зачет не идет. Наоборот, провоцируемый вирусными белками иммунный ответ оказывается для вакцин преимуществом. Кроме того, лишенные собственных генов вирусные векторы, требуют для репродукции вспомогательных вирусов-помощников, что также сильно усложняет производство. Поэтому в современных аденовирусных вакцинах в основном используют векторы первого поколения. Они обеспечивают баланс между эффективностью, простотой производства и требуемой иммуногенностью.
Современные аденовирусные вакцины
Хотя использование аденовирусной технологии и лежит у самых истоков генной терапии, никогда раньше так широко она не использовалась, как в период пандемии COVID-19. Дело в том, что база этой технологии уже была заложена и отточена в предыдущих эпизодах этого сериала — в частности, в эпопее по созданию вакцины от лихорадки Эбола, — и нужно было лишь взять эту технологию и пустить в дело.
От вируса Эбола к коронавирусу
На «Биомолекуле» есть исчерпывающая статья, описывающая историю создания вакцины от вируса Эбола и как на ее основе позже появился «Спутник V», к которой мы и отправляем читателя: «Смертельная зараза: за что мы благодарны лихорадке Эбола и при чем тут “Спутник V”» [30]. А помимо вакцины, от лихорадки Эбола недавно создали также и лекарство: «Инмазеб. Новая страница в истории лечения Эболы» [31].
Различают гомологичный и гетерологичный прайм-бустинг. В первом случае обе «порции» вакцины представляют собой один и тот же компонент, а вот во втором случае — компоненты в «порциях» уже разные. И есть данные, что гетерологичный прайм-бустинг может приводить к более устойчивому иммунитету, чем гомологичный [32].
Janssen vs «ГамЭвак-Комби»
Гетерологичный прайм-бустинг используют против вируса Эбола в схеме вакцинации от компании Janssen и в российской вакцине «ГамЭвак-Комби», разработанной в институте им. Н.Ф. Гамалеи. В первом случае людям сначала вводят векторный аденовирус типа 26 (Ad26), синтезирующий поверхностный гликопротеин вируса. Примерно через восемь недель наступает время второго компонента — генетически модифицированного вируса оспы, несущего гены уже нескольких белков-антигенов от различных вариантов возбудителя лихорадки Эбола.
В вакцине «ГамЭвак-Комби» все реализовано немножко по-другому. Здесь люди вначале получают генетически измененные для экспрессии гена гликопротеина вирусы везикулярного стоматита, а затем уже (как минимум через 21 день) несущие в геноме код того же антигена векторы Ad5. И все это немного напоминает вакцинацию от нового коронавируса, не так ли? Ведь иммунизация Ad5 и Ad26 используется и против этого патогена. Вот только здесь уже в качестве антигена эти векторы производят белок S.
«Спутник V» / «Спутник Лайт»
На данный момент «Спутник V» (разработанный в Центре эпидемиологии и микробиологии имени Н.Ф. Гамалеи) [33] — единственная векторная вакцина от нового коронавируса, в которой реализован режим гетерологичного прайм-бустинга [3]. Интервал дозирования здесь составляет 21 день: первой дозой вводится вектор Ad26, а второй — уже Ad5. Использование вектора Ad26 изначально было продиктовано необходимостью преодоления предсуществующего иммунитета. Дело в том, что наиболее широко использующийся аденовирус 5 серотипа по совместительству является одним из самых распространенных в европейской популяции. Это означает, что в процессе естественного инфицирования множество людей уже сталкивались с ним и потому имеют антитела, выработанные против его белковой оболочки (капсида). Предполагалось, что введение вакцины тем, кто ранее сталкивался с вирусом, будет менее эффективным. Его частицы облепятся специфичными антителами, их входа в клетки не произойдет, антиген не будет синтезироваться, и иммунитет против патогена выработаться не успеет. Однако широкое использование векторных вакцин показало, что специфический иммунитет против целевого антигена все же вырабатывается даже у ранее сталкивавшихся с Ad5-серотипом людей. В этом случае специфичные к капсиду антитела, по всей видимости, просто не успевают нейтрализовывать часть вводимых векторов, — они все же попадают в дендритные клетки, а вместе с ними и в лимфоузлы. Это приводит к тому, что даже повторное введение вакцины вызывает выработку антител и защиту организма от инфекции.
Тем не менее на момент создания первых векторных вакцин, разработчики оглядывались на возможное влияние предсуществующего иммунитета, и искали способы его обойти. Здесь-то привлекательным решением и стал имеющий низкую распространенность серотип Ad26, что, как считалось, может делать его более иммуногенным.
Вакцина от Johnson & Johnson
Однокомпонентная вакцина от Johnson & Johnson использует генетически модифицированный Ad26 против COVID-19. Но, в отличие от «Спутника V» и других подобных препаратов, здесь в геноме вектора заложена конструкция, кодирующая так называемую стабилизированную префузионную форму белка S (рис. 6) [3].
Рисунок 6. S-белки изменяют свою конформацию при связи с мишенью. Форму до взаимодействия называют префузионной (справа), а после взаимодействия и слияния вирусной и клеточной мембран — постфузионной (слева).
В исследованиях на животных показана индукция более высоких уровней нейтрализующих антител на данную конформацию, чем на белок S в его нативной форме [35]. Возможно, это-то и обеспечивает достаточность однократной дозы для эффективности препарата, которая, как показали исследования, вполне удовлетворительна. Через 42 дня после иммунизации эффективность вакцины составляла 92,4%, при этом стойкость иммунных реакций наблюдалась и через 8 месяцев после прививки [3].
Оксфордская вакцина
Вакцина, производимая компанией AstraZeneca и разработанная в стенах Оксфордского университета, использует протокол гомологичного прайм-бустинга с интервалом между дозами в 28 дней. И в первой, и во второй инъекции здесь вводят вектор ChAdOx1 на основе аденовируса шимпанзе Y25-серотипа (выбор вектора продиктован обходом возможного иммунитета к Ad5) [36]. ChAdOx1 экспрессирует ген S-белка и имеет ряд модификаций относительно своего «дикого собрата» Y25. За счет удаления генов E1/E3 он лишен возможности размножаться, а замена участков гена E4 природного вируса на аналогичные от Ad5-серотипа позволяет при производстве получать больше таких частиц. При этом этот вектор уже проходил испытания в составе вакцины против ближневосточного респираторного синдрома, когда разразилась пандемия COVID-19.
Ну а в апреле 2020 года в Соединенном Королевстве начались клинические испытания I фазы препарата уже и против нового коронавируса на его основе. Затем исследования расширили до испытаний фазы III в Бразилии и Южной Африке, в которых участвовали здоровые взрослые в возрасте 18–55 лет, пожилые люди (≥56 лет), медицинские работники и другие лица. Результаты, полученные в четырех независимых клинических испытаниях, продемонстрировали общую эффективность 70,4% (после двух доз) и 64,1% (после одной дозы) [36]. Позднее общая эффективность была скорректирована до 76% (и до 85% у лиц старше 65 лет). Новые данные относятся к исследованию фазы III NCT04516746, в котором приняли участие более 30 тысяч участников.
«Конвидеция» (Convidecia)
Вакцина «Конвидеция» от CanSino Biologics (Тяньцзинь, Китай), также основанная на человеческом Ad5, синтезирующем белок S, была протестирована в Ухане, в рамках II фазы клинических испытаний. В общей сложности 508 взрослых старше 18 лет были иммунизированы однократной дозой в различных концентрациях векторов. Выработка специфических антител была зависимой от дозы, и ее частота составляла 96% при более высокой дозе и 97% при более низкой. Результаты исследования фазы III (NCT04526990) еще не были опубликованы, когда вакцину уже одобрили для использования в Китае [36]. Данный препарат проходил испытания и для одобрения в России, чем занималась компания «Петровакс». По данным пресс-релиза эффективность вакцинации здесь составила 90,6% при хорошей переносимости и высоком профиле безопасности. На этом основании была подана заявка на регистрацию в Минздрав в августе 2021 года и даже предварительно запланировано производство препарата на мощностях компании. Однако с тех пор новостей не было, и текущий статус по этому вопросу неясен.
Загвоздка качества
На бумаге «Спутник V» и его западные аналоги очень схожи: демонстрируют примерно равную эффективность и применяются как на отечественных для производителей рынках, так и в других странах. Но есть между ними одно радикальное различие, ведь «Спутник V» пока не был одобрен для применения ни в США, ни в Евросоюзе.
У них и у нас
Стоит сказать, что препаратам, разработанным на Западе в целом вообще легче пройти «горнило» регуляторного одобрения в США и Европе, и для этого есть вполне объективные причины. Дело в том, что там внедрены и активно используются нормативные стандарты, подразумевающие более высокие требования к качеству и производству, чем те, на которые опираются нынче в России. Ну а поскольку данную улучшенную систему качества стали внедрять более 30 лет назад, то и создание вписывающихся в нее лекарств отработано уже неплохо. В частности, при производстве вакцин Johnson & Johnson и AstraZeneca контролируется буквально всё (как и для продуктов генной и клеточной терапии) [37]: исходное и промежуточное сырье и материалы, банки клеток, каждый этап производства, соответствие конечной субстанции спецификации и т.д. (рис. 7) [22], [38].
Рисунок 7. Основные стадии производства вакцины Johnson & Johnson. Производство аденовирусных частиц состоит из 10 этапов: 1) предварительное культивирование; 2) наработка требуемого количества клеток; 3) продукция вируса в клетках; 4) лизис клеток; 5) очистка от ДНК; 6) осветление культуральной жидкости; 7) анионообменная хроматография; 8) концентрирование и диафильтрация; 9) финальная фильтрация (через мембрану с размером пор 0,22 мкм) и разлив фильтрата в емкости из поликарбоната; 10) замораживание для хранения при температуре −40 °C.
При этом любое отклонение производственных параметров от строгих критериев приемлемости расследуется, а все данные по контролю качества предоставляются по запросу регуляторам. То есть система производства и контроля качества не только очень здорово отработана, но и прозрачна для внутреннего и внешнего контроля. Это делает процесс одобрения лекарств более эффективным, а ведь и регулирующие органы имеют там более сложные регламенты утверждения. Они могут требовать от заявителей предоставления подробностей об эффективности, безопасности, деталях производства препаратов, а также запрашивать дополнительные данные для научных и регуляторных обзоров — всё это затормозило международное признание «Спутника».
Конечно, нельзя сказать, чтобы российское производство сегодня было совсем чуждо всей этой «кухни», но некоторые проблемы, с которыми сталкивались российские площадки, говорят о том, что не всё ладно в датском королевстве. В частности, после визитов аудиторов ВОЗ и ЕМА в Россию был высказан ряд замечаний, после устранения которых планировались повторные аудиты. В связи с началом специальной военной операции и международной изоляцией России неясно, произойдут ли эти аудиты вообще.
Проблемы и решения
Топ-менеджеры компаний производителей «Спутника V» и инсайдеры отмечали производственные сложности, из-за которых приходилось выбраковывать целые серии препарата. Это, например, перекрестная контаминация серотипов Ad5 и Ad26 и появление в вакцине размножающихся вирусов. Первое было связано с неполным разделением производственных потоков, что разные компании решали по-разному. Например, распределением производств серотипов между разными помещениями с отдельными входами для персонала, или вовсе перемещением их на разные заводы, отдаленные друг от друга на сотни километров.
Вторая проблема была более специфична и связана с обменом генетическим материалом между клетками-продуцентами вируса HEK293 и неспособными к размножению вирусами. Их случайная рекомбинация приводила к тому, что в вектор из клеток «возвращался» удаленный из него ген E1, и утраченная способность вируса размножаться вновь восстанавливалась. Такие проблемы вряд ли возможны, например, при производстве вакцины Johnson & Johnson, так как она содержит только один компонент, который производится в специально созданной для этого клеточной линии PER.C6. В таких клетках также присутствует ген E1, но интегрированный фрагмент генома вируса здесь уже меньшего размера, и для восстановления «репродуктивной способности» в нем недостает ключевых элементов. При использовании правильно сконструированных векторов это делает невозможным появление размножающихся вирусов [22], [39], [40]. Что, впрочем, совсем не означает, что западные вакцины не проверяют на их содержание. Более того, такой контроль, наряду с контролем примесей и микробиологической чистоты, «интегрирован» в производство препаратов в соответствии с требованиями американской и европейской фармакопей [22], [38].
Насколько всё плохо?
Как ни странно, ничего смертельного в наличии размножающихся вирусов в вакцинах нет. Более того, они лежат в основе создания некоторых вакцин, так как зачастую имеют преимущество более сильного и продолжительного иммунного ответа. Примерно то же можно сказать и о перекрестной контаминации: реакция на такие препараты, скорее всего, будет немного отличаться профилем иммунного ответа, не более. Это, конечно, если исходить из чисто теоретических соображений, но и из практики применения можно судить о многом. Ведь ныне «Спутником V» вакцинированы уже миллионы людей, причем как в России, так и в других странах, и очевидно, что если бы какие-либо серьезные последствия этого имелись, они бы не остались незамеченными.
В тоже время, нельзя просто так взять и прописать в вакцине отсутствие размножающихся вирусов, если они там есть. Это идет вразрез с принципами, изложенными в руководствах международного совета по гармонизации (ICH), на которые опираются регуляторные органы США и Европы. В них описаны основные требования к разработке, производству и регистрации фармацевтических продуктов. В частности, что характеристики любого лекарственного средства должны быть четко определены и прописаны. То есть если заявлено, что вакцина размножающихся вирусов не содержит, то именно так оно и должно быть. В противном случае нужно не только предоставить данные о количестве таких вирусов, но и об их влиянии на здоровье человека, которое должно быть оценено в соответствующих исследованиях. Нарушение этого правила ставит под вопрос возможное использование «Спутника V» в США и Европе, где такие аспекты для регуляторного одобрения имеют очень большое значение.
EMA — Европейское агентство лекарственных средств — один из основных мировых регуляторов использования лекарств, определяющий их одобрение для применения на территории стран Евросоюза.
ОЭСР — организация экономического сотрудничества и развития — международная организация экономически развитых стран, признающих принципы представительной демократии и свободной рыночной экономики.
В связи с началом специальной военной операции и международной изоляцией России подобные прогнозы, к сожалению, выглядят более чем фантастичными. — Ред.
Эта статья заканчивает большую серию из семи публикаций о генной и клеточной терапии. В этом сериале мы постарались осветить историю отрасли, ее современное состояние и будущие перспективы. Надеемся, читателю стало понятно, что в ней достигнуты впечатляющие успехи, однако она всё еще находится в колыбели. Созданы технологии, способные лечить ранее неизлечимые заболевания, спасшие миллионы людей от коронавируса, но потенциал технологии неизмеримо больше: у генных и клеточных технологий есть возможность в ближайшие десятилетия снизить смертность от сердечно-сосудистых заболеваний, рака, аутоиммунных болезней, редких болезней — и лучшие умы человечества работают над решением этих проблем.
Manufacturing, safety and quality control of vaccines
This article is part of a series of explainers on vaccine development and distribution. Learn more about vaccines – from how they work and how they’re made to ensuring safety and equitable access – in WHO’s Vaccines Explained series.
How a vaccine is approved for production
For more information on the three phases of vaccine clinical trials,click here.
Once a vaccine has reached pre-approval stage following clinical trials, it is assessed by the relevant regulatory body for compliance with quality, safety and efficacy criteria. Following regulatory approval, manufacturers can submit a vaccine to WHO for prequalification (PQ), an assessment process that ensures quality, safety and efficacy and helps the UN and other international procurement organizations determine the programmatic suitability of a vaccine.
During global health emergencies, the WHO Emergency Use Listing Procedure (EUL) may be used to allow emergency use of the vaccine. The EUL exists because, in a pandemic situation, products that could benefit the lives of people all over the world may be prevented from coming to market with sufficient speed. The EUL is a fast-tracked but rigorous process, designed to bring impactful products to all those in need, as quickly as possible, on a time-limited basis and based on a risk-versus-benefit evaluation. The WHO PQ/EUL recommendation may be used by UN agencies such as UNICEF and the Pan American Health Organization Revolving Fund for procurement decisions in low- and middle-income countries. Gavi also relies on WHO EUL/PQ to specify which vaccines its funds may be used to purchase.
How it’s made
Typically, companies will work independently to complete clinical development plans for a vaccine. Once a vaccine is authorized, manufacturing begins to scale up. The antigen (part of the germ that our immune system reacts to) is weakened or deactivated. To form the full vaccine, all ingredients are combined.
The whole process, from preclinical trial to manufacture, can sometimes take over a decade to complete. In the search for a COVID-19 vaccine, researchers and developers are working on several different phases in parallel, to speed up results. It is the scale of the financial and political commitments to the development of a vaccine that has allowed this accelerated development to take place. Also, nations and international health organizations are working together through COVAX to invest in development capacity upfront to streamline the process, as well as to ensure equitable distribution of vaccines.
How it’s packaged
Once the vaccine has been made in bulk quantities’, it is bottled in glass vials and then carefully packaged for safe cold storage and transport.
Vaccine packaging must be able to withstand extreme temperatures, as well as the risks involved in being transported globally. Therefore, vaccine vials are most commonly made from glass, as it is durable and able to maintain its integrity in extreme temperatures.
How it’s stored
Regular refrigerators cannot maintain an even temperature consistently, so specialized medical refrigerators are required for these precious products.
How it’s shipped
To maintain this cold chain, vaccines are shipped using specialized equipment that does not compromise the integrity of the product. Once shipments land in the destination country, refrigerated lorries transport the vaccines from the airport to the warehouse cold room. From there, portable iceboxes are used to transport vaccines from the cold room to regional centres where they’re stored in refrigerators. If vaccination takes place outside of the regional facility, the final step often requires portable iceboxes to transport the goods to local areas for vaccination campaigns. New technologies have invented some portable devices that can keep vaccines at their cold temperature for several days without needing electricity.
Once vaccines start being administered, national authorities and WHO constantly monitor for – and establish the severity of – any possible adverse side effects and responses from people who have received the vaccine. The safety of the vaccine is paramount, with regular assessments and post-approval clinical studies to report on its safety and effectiveness.
Studies are often conducted to determine how long a given vaccine remains protective.
Vaccine efficacy, effectiveness and protection
This article is part of a series of explainers on vaccine development and distribution. Learn more about vaccines – from how they work and how they’re made to ensuring safety and equitable access – in WHO’s Vaccines Explained series.
COVID-19 vaccines have proven to be safe, effective and life-saving. Like all vaccines, they do not fully protect everyone who is vaccinated, and we do not yet know how well they can prevent people from transmitting the virus to others. So as well as getting vaccinated, we must also continue with other measures to fight the pandemic.
Vaccine efficacy and effectiveness
All COVID-19 vaccines approved by WHO for emergency use listing have been through randomized clinical trials to test their quality, safety and efficacy. To be approved, vaccines are required to have a high efficacy rate of 50% or above. After approval, they continue to be monitored for ongoing safety and effectiveness. But what is the difference between efficacy and effectiveness?
A vaccine’s efficacy is measured in a controlled clinical trial and is based on how many people who got vaccinated developed the ‘outcome of interest’ (usually disease) compared with how many people who got the placebo (dummy vaccine) developed the same outcome. Once the study is complete, the numbers of sick people in each group are compared, in order to calculate the relative risk of getting sick depending on whether or not the subjects received the vaccine. From this we get the efficacy – a measure of how much the vaccine lowered the risk of getting sick. If a vaccine has high efficacy, a lot fewer people in the group who received the vaccine got sick than the people in the group who received the placebo.
So, for example, let’s imagine a vaccine with a proven efficacy of 80%. This means that – out of the people in the clinical trial – those who received the vaccine were at a 80% lower risk of developing disease than the group who received the placebo. This is calculated by comparing the number of cases of disease in the vaccinated group versus the placebo group. An efficacy of 80% does not mean that 20% of the vaccinated group will become ill.
Vaccine protection and timing
Vaccines offer strong protection, but that protection takes time to build. People must take all the required doses of a vaccine to build full immunity. For two-dose vaccines, vaccines only give partial protection after the first dose, and the second dose increases that protection. It takes time before protection reaches its maximum level a few weeks after the second dose. For a one-dose vaccine, people will have built maximum immunity against COVID-19 a few weeks after getting vaccinated.
Vaccine protection and infection
Vaccines can stop most people from getting sick with COVID-19, but not everyone.
Even after someone takes all of the recommended doses and waits a few weeks for immunity to build up, there is still a chance that they can get infected. Vaccines do not provide full (100%) protection, so ‘breakthrough infections’ – where people get the virus, despite having been fully vaccinated – will occur.
If vaccinated people do get sick, they are likely to have milder symptoms, in general ‘It is very rare for someone vaccinated to experience severe illness or die.
Vaccine protection and transmission
COVID-19 vaccines are crucial tools in the pandemic response and protect against severe disease and death. Vaccines provide at least some protection from infection and transmission, but not as much as the protection they provide against serious illness and death. More evidence is needed to determine exactly how well they stop infection and transmission.
After being vaccinated, individuals should continue taking simple precautions, such as physical distancing, wearing a mask, keeping rooms well ventilated, avoiding crowds, cleaning hands, and coughing into a bent elbow or tissue. Get tested if you are sick, even if you’ve been vaccinated. Check local advice where you live and work. Do it all!
Vaccine protection and variants
When cases increase and transmission accelerates, it’s more likely that new dangerous and more transmissible variants emerge, which can spread more easily or cause more severe illness.
Based on what we know so far, vaccines are proving effective against existing variants, especially at preventing severe disease, hospitalization and death. However, some variants are having a slight impact on the ability of vaccines to guard against mild disease and infection.
Vaccines are likely staying effective against variants because of the broad immune response they cause, which means that virus changes or mutations are unlikely to make vaccines completely ineffective.
WHO continues to constantly review the evidence and will update its guidance as we find out more. For the latest updates on what we know about the COVID-19 variants, read our latest weekly epidemiological updates and our explainer on ‘the effects of virus variants on COVID-19 vaccines’.
One of the best ways of guarding against new variants is to continue applying tried-and-tested public health measures and rolling out vaccines. All COVID-19 vaccines approved for emergency use listing by WHO have been thoroughly tested and proven to provide a high degree of protection against serious illness and death. As stronger virus variants emerge, it’s important to take your vaccine when it’s your turn.
