The first COVID-19 vaccine to go into any American arms outside of a trial — and the first to be fully approved by the Food and Drug Administration — is Pfizer’s mRNA vaccine, which was designed and developed by the German biotech company BioNTech. Here, we give a rundown of basic facts about the vaccine and an overview of how it works.
Vaccine name: BNT162b2, marketed as Comirnaty
Design type: mRNA
Dose number: 2, 21 days apart, with a third dose recommended for certain immunocompromised people
Efficacy: 91% efficacy in preventing symptomatic COVID-19 in people 16 years of age or older a week or more after receipt of the second dose.
Safety: No serious safety concerns reported other than some rare allergic reactions and a likely, but rare, association with heart inflammation. The shots routinely elicit a fairly strong temporary reaction in many people that can include injection site pain, fatigue, headache and chills.
Expected dose availability: Worldwide, up to 50 million doses, or enough for approximately 25 million people, by the end of 2020, with up to 1.3 billion doses expected in 2021.
Timeline: First doses were administered in December 2020 to prioritized populations, following the FDA’s emergency use authorization on Dec. 11.
Operation Warp Speed involvement: No support for the trials or research and development, but the U.S. government inked a $1.95 billion deal in July as part of OWS to buy 100 million doses. In December and February the U.S. announced agreements to purchase another 100 million doses each, for a total of 300 million doses to be delivered by the end of July 2021.
Storage considerations: Ultracold freezer temperatures of -80ºC to -60ºC (-112ºF to -76ºF) for long-term storage, with up to two weeks at standard freezer temperatures; after thawing, vaccine vials can be stored at refrigerator temperatures for up to five days.
The Pfizer/BioNTech vaccine is the first COVID-19 vaccine authorized for use in the U.S. and the first to be fully approved by the FDA. The companies released promising interim results from a phase 3 trial on Nov. 9, and on Nov. 18 announced an efficacy of 95% in preventing disease.
Two days later, the company submitted its application to the FDA to receive an emergency use authorization, or EUA, for its vaccine in people 16 years of age and older. The FDA conducted a thorough review — including an analysis of the raw data — of the vaccine’s safety and efficacy, and issued an EUA on Dec. 11.
A day prior to the FDA’s authorization, an outside panel of experts advising the agency also backed the vaccine in a 17 to 4 vote, with one abstention, that based on the evidence available, “the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older.”
Based on additional clinical trial data from adolescents, the FDA amended its EUA for the vaccine on May 10 to include teens ages 12 to 15. The agency also revised the EUA on Aug. 12 to allow for third doses of the vaccine in certain immunocompromised people.
On Aug. 23, the FDA granted full approval to the vaccine for people 16 years of age and older. The vaccine remains available under emergency use to children as young as 12 and as a third dose to select immunocompromised people.
What is in the vaccine and how does it work?
As with most other COVID-19 vaccine designs, the Pfizer/BioNTech mRNA vaccine works by triggering an immune response against the spike protein of the SARS-CoV-2 virus, which sits on the surface of the virus and is what the virus uses to enter cells.
The vaccine is made of modified messenger RNA, or mRNA, wrapped in a special blend of fatty molecules known as lipid nanoparticles. The mRNA provides instructions for cells to make their own spike proteins, prompting the body to generate protective antibodies and activate T cells. The lipids help deliver the RNA into cells and prevent it from being degraded too quickly.
As the Centers for Disease Control and Prevention has explained, there is no way to catch COVID-19 from this type of vaccine because the vaccine is not made of a virus. And because the mRNA from the vaccine doesn’t enter the nucleus — the part of the cell that houses DNA — it “does not affect or interact with a person’s DNA,” contrary to some online rumors.
How was the vaccine developed?
Early phase clinical trials showed that two leading mRNA designs triggered neutralizing antibody responses that were better than those from people recovering from natural COVID-19 infection, with no serious adverse events.
But one candidate — BNT162b2, which prompts cells to make a full-length spike protein — did so with fewer side effects than the other. Based on the trial results and preclinical tests in animals, the companies decided to move forward to a combined phase 2/3 randomized controlled trial testing two 30 microgram doses of BNT162b2 on volunteers.
The phase 2/3 trial began in late July 2020, ultimately enrolling around 46,000 people in the U.S., Argentina, Brazil, Germany, South Africa and Turkey. Enrollment was expanded past the 30,000 initial target in September 2020 to include people infected with HIV, hepatitis B and hepatitis C, and to add teens as young as 16 years old. In October 2020, the age requirement was lowered to 12 years old. Because of the limited data available on this population at the time of submission, however, Pfizer did not ask to include the 12- to 15-year-old age group in its original EUA request.
How effective is the vaccine?
In the updated trial results reported to the FDA for full approval, the Pfizer/BioNTech vaccine was 91% effective in preventing symptomatic disease at least a week after the second dose in people 16 years of age and older.
This does not mean that the vaccine works 91% of the time or that 9% of vaccinated people will fall ill with COVID-19. Instead, as Emory University biostatistician Natalie Dean and the World Health Organization have explained, the percentage refers to a relative reduction in risk, such that a vaccinated person is 91% less likely to get sick compared with an unvaccinated person.
In the updated analysis, which included around 20,000 participants each in the vaccine and placebo groups, there were 833 symptomatic COVID-19 cases in the placebo group and 77 in the vaccine group.
Pfizer previously reported an efficacy of 95% in preventing disease in people 16 years of age and older, based on 162 cases of symptomatic COVID-19 in the placebo group and eight in the vaccine group. It was this data that served as the basis of the FDA’s initial EUA for the vaccine in December 2020.
According to the FDA’s summary explaining its approval decision, vaccine efficacy for the updated trial was similar across a variety of demographics, including gender, ethnic groups and those at high risk of severe COVID-19.
Protection against severe disease was also very high. Depending on the case definition for severe COVID-19, the vaccine was either 95% or 100% effective in the updated trial.
Vaccine efficacy, which is the metric measured in a randomized controlled trial, is different from vaccine effectiveness, which refers to the real-world performance of the vaccine, as measured in observational studies. Vaccines may not do quite as well in a wider population outside the idealized conditions of a trial.
Efficacy figures also only reflect the vaccine’s performance after a certain amount of time and against the type of virus circulating in the population at the time of testing. In the case of the Pfizer/BioNTech vaccine, that did not include the highly contagious delta variant, but did include some locations where the beta variant was prevalent; the period of follow-up was up to around six months after receiving a second dose.
At the same time, observational studies used to estimate effectiveness are more prone to bias compared with randomized controlled trials.
Since the vaccine’s rollout, numerous observational studies have demonstrated the Pfizer/BioNTech vaccine’s effectiveness in the real world, including against the delta variant, although there may be a decline in protection against infection and mild disease compared with previous viral variants.
A study published in the New England Journal of Medicine in July, for example, found that the two-dose vaccine was 88.0% effective in preventing symptomatic disease with delta in the U.K., down from 93.7% against the previously dominant alpha variant.
In a study of New York residents, about half of whom were immunized with the Pfizer/BioNTech vaccine, vaccine protection against infection fell from 92% to 80% between early May and late July. Another study of nursing home residents from across the U.S. found that the effectiveness of the Pfizer/BioNTech vaccine against infection declined from 74% in the pre-delta era to 52% with delta.
There is little sign, however, of a similar drop in protection against serious disease, hospitalization or death. In the New York study, vaccine protection against hospitalization remained steady, at around 92% to 95%. Another evaluation, which pulled information from across 18 U.S. states, found the Pfizer/BioNTech and Moderna vaccines stayed 84% to 86% effective in preventing hospitalization for 24 weeks.
It remains unknown how long vaccine protection lasts. For some people who are immunocompromised, data suggest that two doses may be insufficient and those individuals might benefit from an additional dose.
For people who are healthy, Pfizer is conducting additional studies to evaluate the safety and efficacy of a third “booster” dose of its vaccine. In late August, the company announced positive results of giving a booster — an increase in neutralizing antibodies with similar side effects to the two-dose regimen — and has started to submit this data to the FDA for approval.
Evidence suggests people vaccinated with the Pfizer/BioNTech vaccine who become infected with the coronavirus can pass it on to others, although they are less likely to do so compared with unvaccinated people.
How safe is the vaccine?
In clinical trials and in subsequent safety monitoring, the Pfizer/BioNTech vaccine has been shown to be very safe.
While many people experience unpleasant side effects, the vaccine only very rarely appears to cause more serious problems.
This includes serious allergic reactions, such as anaphylaxis, and an increased risk of inflammation of the heart muscle (myocarditis) or its surrounding tissue (pericarditis). Both of these adverse events, while potentially dangerous, are uncommon and treatable.
Anaphylaxis refers to a life-threatening reaction that usually occurs within seconds or minutes of exposure to an allergic substance. All vaccination sites are equipped to deal with allergic reactions.
People getting the vaccine should be prepared for irksome side effects, including pain, redness and swelling at the site of injection, as well as fatigue, headache, muscle pain, chills, joint pain and fever.
The only people the FDA says should not receive the Pfizer/BioNTech vaccine are those who have had a serious allergic reaction to a previous dose of the vaccine or one of its ingredients. The CDC advises not getting the Pfizer/BioNTech vaccine if you have had any kind of immediate reaction, even if not severe, to a dose of the vaccine or one of its ingredients, such as polyethylene glycol.
The agency also recommends consulting with your physician if you have ever had an immediate allergic reaction to other vaccines or injectable therapies.
Data presented to the CDC advisory committee showed a rate of 5.0 cases of anaphylaxis per million doses of the Pfizer/BioNTech vaccine, as of July 31, which is slightly higher than 1 to 2 per million instances that occur with other vaccines. The crude estimated frequency of anaphylaxis, as reported in the FDA’s summary accompanying the approval, is 6.0 cases per million doses.
In late June, the CDC’s Advisory Committee on Immunization Practices concluded there is a “likely association” between COVID-19 mRNA vaccination and myocarditis and pericarditis in teens and young adults.
As of Aug. 18, the agency says there have been 1,339 preliminary reports of either condition in people 30 years old or younger following immunization with any COVID-19 vaccine.
Health officials have emphasized that the potential vaccine-related myocarditis and pericarditis cases are rare and the benefits of vaccination still outweigh the risks. Early evidence, ACIP said, suggests these myocarditis cases are less severe than typical ones. The CDC has also noted that most patients who were treated “responded well to treatment and rest and quickly felt better.”
According to an FDA Q&A, the agency has concluded that the safety surveillance data “demonstrate increased risks” of myocarditis and pericarditis following vaccination with the Pfizer/BioNTech vaccine.
In its approval summary, the FDA said the reporting rates for confirmed cases of myocarditis or pericarditis are higher in males under the age of 40 and are highest in male teens 12 to 17 years of age, at approximately 65 cases per million doses administered. The conditions are also more common after the second dose and within a week of vaccination. “Although some cases of vaccine-associated myocarditis/pericarditis required intensive care support,” the FDA summary reads, “available data from short-term follow up suggest that most individuals have had resolution of symptoms with conservative management.”
The agency conducted its own benefit-risk assessment and concluded that even in a “worst-case” scenario, in which myocarditis and pericarditis cases were more frequent than currently observed, the vaccine was less effective than expected and COVID-19 transmission was low, the benefits of vaccination would outweigh the risks.
A study from Israel, published in the New England Journal of Medicine on Aug. 25, similarly identified vaccination with the Pfizer/BioNTech vaccine as being associated with an elevated risk of myocarditis, at the rate of 2.7 additional cases per 100,000 people. But that risk was still much lower than the risk of the same condition in people who contracted the coronavirus, which was at a rate of 11 additional cases per 100,000 people.
The FDA is requiring Pfizer to conduct six studies to better understand the risk of the inflammatory heart conditions after vaccination. The CDC is also conducting its own survey to investigate potential long-term effects.
Why does the vaccine need to be kept so cold?
The extreme cold is necessary to keep the highly sensitive lipid-encapsulated RNA molecules from degrading. Logistically, this cold chain requirement poses an extra hurdle in distributing the vaccine, since many potential vaccination sites lack the appropriate ultracold freezers and may not have a ready source of dry ice.
Pfizer has tried to mitigate some of these challenges by creating specialized “thermal shippers” for its vaccine that will maintain ultracold temperatures for up to 10 days if unopened and can store vials for as long as a month if refilled every five days with dry ice.
On Feb. 25, the FDA also began allowing the vaccines to be shipped or stored at regular freezer temperatures for up to two weeks, following data showing that the doses would remain stable under such conditions.
Rival company Moderna, which also used an mRNA design for its COVID-19 vaccine candidate, also requires freezing temperatures, but they are less severe, due to differences in the particular lipid nanoparticles used. The company announced in November that its vaccine should remain stable long-term at standard freezer temperatures and should last for 30 days in a refrigerator.
Editor’s note: This story will be updated as necessary.
Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over FactCheck.org’s editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.