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. A third “booster” dose is also recommended for everyone 12 years of age and older, as is a fourth dose or second “booster” for people over the age of 50 and those who are immunocompromised.
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 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.
Doses administered: As of May 22, more than 344 million doses have been administered in the U.S. For the latest vaccination information, see the CDC COVID Data Tracker.
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 2020 as part of OWS to buy 100 million doses, with additional subsequent purchase agreements.
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, undiluted vaccine vials can be stored at refrigerator temperatures for up to a month.
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, 2020 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, 2020.
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, 2021, to include teens ages 12 to 15. The agency also revised the EUA on Aug. 12, 2021, to allow for third doses of the vaccine in certain immunocompromised people, given 28 days after the second dose.
On Aug. 23, 2021, 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. A distinct pediatric version of the vaccine, with one-third as much mRNA, is authorized for children ages 5 through 11. For more on that vaccine, see “A Guide to Pfizer/BioNTech’s Pediatric COVID-19 Vaccine for Kids 5-11.”
The FDA has also authorized third doses for non-immunocompromised people, given five or more months after the second shot. After initially restricting third-dose “booster” eligibility to people 65 years of age and older and adults at higher risk, the agency expanded booster access to all adults on Nov. 19, 2021. A CDC advisory committee concluded at the time that anyone 50 years of age and older or with risk factors “should” receive one, while adults below 50 without risk factors “may” receive one.
But with news of the fast-spreading omicron variant, the CDC began recommending boosters to all adults on Nov. 29. On Dec. 9, the FDA extended authorization of a third booster to 16- and 17-year-olds and to everyone 12 years of age and older on Jan. 3.
On March 29, relying primarily on data from Israel, the FDA and CDC began allowing immunocompromised people and those over the age of 50 to receive a second mRNA booster four months or more after the previous dose. Citing a steady rise in cases and a “substantial increase in hospitalizations for older Americans,” the CDC said on May 19 that all people over the age of 50 and the immunocompromised “should” get a second booster.
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.
Pfizer is conducting other studies in children below the age of 12.
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 or omicron variants, 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 has been a decline in protection against infection and mild disease compared with previous viral variants.
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 2021, the company announced positive results of giving a booster — an increase in neutralizing antibodies with similar side effects to the two-dose regimen.
In September 2021, the FDA authorized a booster dose, given at least six months after the initial two-dose series, for the elderly and other populations at increased risk.
In October 2021, Pfizer released clinical trial data showing a booster reduced the chance of falling ill with COVID-19 by 95.6% compared with those who were fully vaccinated but had not received a booster. The FDA expanded booster eligibility to all adults in mid-November 2021 and extended it to 16- and 17-year-olds on Dec. 9, 2021.
On Jan. 3, the FDA authorized boosters of the Pfizer/BioNTech vaccine for people as young as 12 years of age and also shortened the interval for the booster to five months after the second dose. Two days later, the CDC advisory committee voted in favor of those changes, recommending that everyone 12 years of age and older should receive a booster — advice the agency also endorsed.
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.
Against omicron, which was first recognized in southern Africa in November 2021, the Pfizer/BioNTech vaccine is not very good at preventing infection and mild disease. It still provides relatively good protection against more serious illness, though, and boosters increase this protection.
A CDC study found that during the omicron wave, adults who had received two doses of the Pfizer/BioNTech or Moderna vaccines had a 79% lower risk of dying or needing a ventilator if hospitalized with COVID-19, compared with unvaccinated adults. Those who had received a booster vaccine dose as well had a 94% lower risk.
Data presented to the FDA’s vaccine advisory committee on April 6 show that within two months of the first two doses of an mRNA vaccine, adults had a 79% lower risk of COVID-19 hospitalization compared with unvaccinated people. That fell to 54% after four to six months, but a booster dose increased protection to 88% (see summary on slide 32).
On March 29, the FDA and CDC began permitting immunocompromised people and those over the age of 50 to get a fourth mRNA dose, or second booster, four months or more after the last dose. The decision was based largely on data from Israel, which, while limited, suggested improved protection against severe COVID-19 for people 60 years and older after a second mRNA booster.
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, 2021, 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 2021, 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.
Based on data collected through August 2021, the reporting rates of either condition in the U.S. are highest in males 16 to 17 years old after the second dose of the Pfizer/BioNTech vaccine (105.9 cases per million doses), followed by 12- to 15-year-old males (70.7 cases per million). The rate for 18- to 24-year-old males was 52.4 cases per million doses of the Pfizer/BioNTech 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.
The agency conducted its own benefit-risk assessment in its approval summary 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, 2021, 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, 2021, 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. In May 2021, the agency extended the time undiluted vials could be kept in a refrigerator to a month, up from the original five days.
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 2020 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.