Vaccines stimulate the human body’s own protective immune responses so that, if a person is infected with a pathogen, the immune system can quickly prevent the infection from spreading within the body and causing disease. In this way, vaccines mimic natural infection but without actually causing the person to become sick.
For SARS-CoV-2, antibodies that bind to and block the spike protein on the virus’s surface are thought to be most important for protection from disease because the spike protein is what attaches to human cells, allowing the virus to enter our cells. Blocking this entrance prevents infection.
Not all people who are infected with SARS-CoV-2 develop disease (Covid-19 is the disease caused by the virus SARS-CoV-2). These people have asymptomatic infection but can still transmit the virus to others.
In general, most vaccines do not completely prevent infection but do prevent the infection from spreading within the body and from causing disease. Many vaccines can also prevent transmission, potentially leading to herd protection whereby unvaccinated people are protected from infection by the vaccinated people around them because they have less chance of exposure to the virus. We are still learning whether or not the current Covid-19 vaccines prevent transmission of SARS-CoV-2. It is likely they reduce the risk of virus transmission but probably not completely in everyone. This is one of the reasons why it will still be important for people to continue wearing masks and practicing physical distancing, even after being vaccinated.
The safety and efficacy of a vaccine are determined through clinical trials. Clinical trials are studies that are typically conducted in three phases to assess the safety and efficacy of vaccines in increasingly larger numbers of volunteers.
Phase 1 clinical trials assess the safety and dosage of a vaccine in a small number of people, typically a dozen to several dozen healthy volunteers. Whether a vaccine stimulates immune responses is often assessed in a phase 1 study but this is better assessed in phase 2 studies, which typically involve hundreds of people including some special groups such as children, people with pre-existing conditions such as heart disease, and older adults. Vaccine safety is also assessed in phase 2 studies, in which adverse events not detected in phase 1 trials may be identified because a larger and more diverse group of people receive the vaccine. However, only in much larger phase 3 clinical trials can it be demonstrated whether a vaccine is actually protective against disease and safety is more fully assessed.
Phase 3 clinical trials often include thousands of volunteers, and for Covid-19 vaccines involve tens of thousands (30,000 to 45,000 people in some of the phase 3 trials). In phase 3 trials, participants are randomized to receive either the viral vaccine or a placebo vaccine (sometimes a vaccine against another disease or a harmless substance like saline). Randomization is a process to determine who receives the vaccine and who receives the placebo without any bias, like flipping a coin. To further prevent any bias in interpreting the study data, participants and most of the investigators will not know if an individual received the vaccine or placebo. The participants are then followed to see how many in each group get the disease. If the vaccine is efficacious, many fewer people who received the viral vaccine will get the disease compared to those who received the placebo vaccine. It takes time for cases of disease to accumulate so that we can be confident there is a true difference between the two groups, and this is why these phase 3 trials often take time. Another major goal of phase 3 trials is assessing safety, both short-term (e.g., fever, tenderness, muscle aches) and long-term (e.g., autoimmune conditions or enhanced disease following infection).
After a vaccine is approved and in more widespread use, it is critically important to continue to monitor for both safety and effectiveness. Some very rare side effects may only be detectable when large numbers of people have been vaccinated. Safety concerns that are discovered at this late stage could lead a licensed vaccine to be withdrawn from use, although this is very rare. The rare allergic (anaphylactic) reactions seen with the mRNA Covid-19 vaccines were not identified in the phase 3 trials but only after more widespread use.
The best information on the side effects of the Pfizer-BioNTech and Moderna mRNA vaccines comes from the large phase 3 trials that served as the basis for the Emergency Use Authorizations. The most common side effects of both vaccines are what is called reactogenicity. These are expected side effects and caused by local inflammation (redness and swelling) at the site of injection or more generalized reactions such as fever and muscle aches. For both the Pfizer-BioNTech and Moderna vaccines, these reactogenic side effects were mild to moderate, occurred up to two days after vaccination, and do not have any long-term consequences. For the Pfizer mRNA vaccine, the most common side effects were soreness or redness at the site of injection (84% of vaccine recipients), fatigue (63%), headache (55%), muscle pain (38%), chills (32%), joint pain (24%), and fever (14%). Side effects following receipt of the Moderna mRNA vaccine were similar but with slightly different frequencies. The most common side effects were soreness or redness at the site of injection (92%), fatigue (69%), headache (63%), muscle pain (60%), joint pain (45%), and chills (43%).
More severe allergic reactions have occurred more rarely in some people immediately following receipt of one of the mRNA vaccines. In a recent analysis conducted by the Centers for Disease Control and Prevention, 10 cases of anaphylaxis were reported after administration of 4,041,396 first doses of the Moderna Covid-19 vaccine between December 21, 2020 and January 10, 2021. This was an incidence of 2.5 cases of severe allergic reactions per one million doses administered. For this reason, the mRNA vaccines should only be administered in a setting capable of managing and treating anaphylactic reactions. We still do not know the exact cause of these reactions but some think it may be a reaction to the fatty coat that surrounds and protects the mRNA in the vaccine, specifically polyethylene glycol, a compound found in many products including skin creams and toothpaste and that has been associated with allergic reactions. People who have an immediate allergic reaction to the first vaccine dose should not receive additional doses of either mRNA Covid-19 vaccine.
While some protection may be conferred after a single dose of the Pfizer-BioNTech and Moderna mRNA vaccines, this protection is far less than after two doses. The second dose acts as a booster, better preparing the immune system to fight infection. All people should receive two doses of these vaccines.
The scientific data from the large phase 3 trials of the Pfizer-BioNTech and Moderna Covid-19 vaccines demonstrated high protective efficacy when the second dose was administered at a precise interval following the first dose: 21 days for the Pfizer-BioNTech vaccine and 28 days for the Moderna vaccine. For this reason, the second Covid-19 vaccine dose should be administered as close to the recommended interval as possible. However, current challenges with vaccine availability may make this not possible. The Centers for Disease Control and Prevention states that the second dose of the Pfizer-BioNTech and Moderna Covid-19 vaccines may be administered up to 6 weeks (42 days) after the first dose when it is not possible to adhere to the standard schedule but notes that there are limited data on the efficacy of mRNA vaccines administered beyond this time.
Again, the scientific data from the large phase 3 trials of the Pfizer-BioNTech and Moderna Covid-19 vaccines demonstrated high protective efficacy when the second dose was the same vaccine as the first dose. These vaccines are not interchangeable and the safety and efficacy of combinations of vaccines have not been evaluated. However, the Centers for Disease Control and Prevention recently stated that, in exceptional situations in which the first-dose vaccine product cannot be determined or is no longer available, any available mRNA Covid-19 vaccine may be administered to complete the mRNA Covid-19 vaccination series.
Yes. Until we substantially reduce community transmission of SARS-CoV-2, and see hospitalizations and deaths dramatically decrease, we still need to wear masks and practice physical distancing even after vaccination. The vaccine is not 100% effective and we still do not know if someone who was vaccinated can develop asymptomatic infection and transmit the virus. Although the phase 3 clinical trials were designed to determine whether vaccinated individuals are protected against disease, it will also be important to understand whether vaccinated individuals are less likely to transmit the virus. This is likely but not ensured. If a vaccine not only protects against disease but reduces transmission, and continues to do so for many years, we are likely to reach a state of herd protection when masks and physical distancing will no longer be required. Herd protection is achieved when a sufficient proportion of the population is made non-infectious through vaccination or natural infection so that the likelihood of an infectious individual transmitting to a susceptible individual is very low.
All viruses mutate over time but several variants of SARS-CoV-2 with multiple mutations, particularly in the gene that encodes for the spike protein, have been identified that have become more prevalent, including variants from the United Kingdom, South Africa, and Brazil. The best evidence of whether the Pfizer-BioNTech and Moderna vaccines provide less protection against these variants will be if we identify people who become infected with one of the variants after receiving two vaccine doses. Before that, we can learn from studies in the laboratory. Recent studies suggest that both vaccines are effective against these variants but may be slightly less protective against the South African variant. However, much remains to be learned. Both vaccine manufactures are working on modified vaccines to better protect against the South African SARS-CoV-2 variant.
It is not clear at this point in time when vaccines will be available to everyone, but a reasonable guess may be by the end of the summer or early fall of this year. The timeline depends on how rapidly vaccine doses can be produced and distributed. Importantly, the public will need to trust a vaccine and be willing to be vaccinated to have a public health impact. Building trust in a vaccine for SARS-CoV-2, particularly in communities with long-standing mistrust of the government and scientific experiments, is critical.
Although the large phase 3 trials of the Pfizer-BioNTech and Moderna Covid-19 vaccines did not include pregnant women, eligible pregnant women may be vaccinated. The two mRNA vaccines are not contraindicated during pregnancy. Pregnant women should consider the risks of Covid-19, which may be more severe in pregnant women, and the uncertain risk of vaccination. More information on the safety and efficacy of Covid-19 vaccines in pregnant women will become available over time.
While children are less likely to develop severe disease and die from Covid-19, there are several reasons for ensuring that eventually there is a vaccine that is safe and effective for children. Although rare, some children may develop severe disease or die from Covid-19. Children have also developed a severe inflammatory syndrome, called multisystem inflammatory syndrome in children. Children may be important transmitters of SARS-CoV-2 and vaccinating them with a vaccine that reduces transmission could be important in controlling the pandemic. Finally, having a safe vaccine for children will build confidence towards opening up schools and learning centers for in-person educational processes.
Both the Pfizer-BioNTech and Moderna vaccines are being studied in children as young as 12 years of age. These studies typically involve several thousand children, and not the tens of thousands studied in phase 3 trials in adults. Assuming the vaccines are safe and effective, the vaccines will be studied in younger and younger children. Studies of the Moderna vaccine in children 1 to 11 years of age may start soon.
We do not yet know how long protection lasts following vaccination but it will be critically important to measure long-term protection (at least two years) in the phase 3 trials and by following people who have been vaccinated outside of the trials. We are still learning about the duration of protection following infection with SARS-CoV-2 and it is too early to tell how long protection will last. There have already been cases where individuals have been shown to be infected twice but most often the second illness was mild or without any symptoms. This is what we would expect with an immune response that protects against disease but not infection.
Yes. The Centers for Disease Control and Prevention recommends that people who have had Covid-19 should still be vaccinated because of the severe health risks associated with Covid-19 and the fact that reinfection is possible. People who were treated for Covid-19 with monoclonal antibodies or convalescent plasma should wait 90 days before getting a Covid-19 vaccine.
No, it is not possible to get Covid-19 from vaccines. Vaccines against SARS-CoV-2 use inactivated virus, parts of the virus (e.g., the spike protein), or a gene from the virus. None of these can cause Covid-19.
Yes, it is very important to get the influenza vaccine, particularly this season when both influenza viruses and SARS-CoV-2 can infect people. We still do not know how these two viruses will interact but people can get infected with both viruses and this will likely cause more severe disease and possibly death. Reducing the number of people who get severe influenza and require hospitalization will also help ensure that the health care system, hospitals and intensive care units will not be overwhelmed should there be an increase in Covid-19 cases this fall and winter.
Several different types of vaccines against SARS-CoV-2, the virus that causes the disease Covid-19, are in use or in development. Many manufacturers around the world are working on this global problem. This means that there will continue to be different types of SARS-CoV-2 vaccines and they may work differently in different people. Some are based on traditional methods for producing vaccines and others on newer methods.
Both of the SARS-CoV-2 vaccines that have received Emergency Use Authorization in the United States, manufactured by Pfizer-BioNTech and Moderna, use one of the most novel approaches: The gene for the spike protein can be used directly as a vaccine in the form of DNA or messenger RNA (mRNA).
One of the more traditional ways of making a viral vaccine is to inactivate (kill) the virus with chemicals, such as is done with the flu vaccine, inactivated polio or hepatitis A vaccines, so that the virus can no longer multiply. Several inactivated SARS-CoV-2 vaccines are in use, such as those produced by the Chinese vaccine manufacturers Sinopharm and Sinovac Biotech, and others are in development. Other vaccines are based on just a part of the bacteria or virus, typically one or more proteins, such as the vaccines for whooping cough (pertussis) and hepatitis B virus. For SARS-CoV-2 vaccines that focus on a part of the virus, this means the spike protein on the surface of the virus. A protein-based vaccine produced by Novavax is being studied in a large trial in the United States.
Newer vaccine types include what are called viral vector vaccines, in which the SARS-CoV-2 gene for the spike protein is inserted into another harmless virus to deliver the gene to human cells where the spike protein is produced. The spike protein then stimulates immune responses. The most common viral vectors are adenoviruses, which typically cause common cold-like symptoms in people but are further weakened for vaccines so they cannot cause any disease at all. The adenovirus vector vaccine for SARS-CoV-2, developed and produced by the University of Oxford and AstraZeneca, is in use in several countries, including Britain, India, Brazil, and Mexico. Other adenovirus vector vaccines are in advanced clinical testing (phase 3 clinical trials), such as the vaccine produced by Johnson & Johnson that may be protective following a single dose.
Drugs and vaccines have to be approved by the Food and Drug Administration (FDA) to ensure that only safe and effective products are available to the American public. In situations when there is good scientific reason to believe that a drug is safe and is likely to treat or prevent disease, the FDA may authorize its use even if definitive proof of the efficacy of the drug is not known, especially for diseases that cause high mortality. On December 11, 2020 the FDA issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech Covid‐19 Vaccine and on December 18, 2020 the FDA issued an EUA for the Moderna Covid-19 vaccine. We expect that the Pfizer-BioNTech and Moderna vaccines will receive full approval, called a Biologics License Application, in the first half of 2021.
The bar for ensuring safety of a vaccine is higher than for a therapeutic to treat an ill person. Vaccines are given to potentially millions of healthy people, unlike drugs for sick people, and loss of trust in a vaccine for SARS-CoV-2 could spill over into loss of trust in other vaccines, seriously jeopardizing public health.
Traditionally, it has taken many years to develop a vaccine, confirm its safety and efficacy, and manufacture the vaccine in sufficient quantities for public use. This timeline has been substantially shortened for SARS-CoV-2 vaccines. There are several ways this has been made possible. First, some clinical trials have combined phases 1 and 2 to assess safety and immune responses. Second, because of the high number of new cases of Covid-19 in many places, differences in disease risk between those who received the viral vaccine and those who received the placebo or comparison vaccine can be measured more quickly than in the absence of a pandemic. Third, the United States government and others heavily invested in building the manufacturing capacity to produce large numbers of vaccine doses before the findings of the phase 3 trials were available. Typically, vaccine manufacturers wait until the phase 3 trial is completed and shows safety and efficacy before making such a large investment in manufacturing capacity. None of these factors that contribute to the accelerated development of a vaccine for SARS-CoV-2 imply that safety, scientific or ethical integrity are compromised, or that short-cuts were made.