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Comparing the COVID-19 Vaccines: How Are They Different?

BY KATHY KATELLA June 20, 2022

Information to help you make your best choice.

[Originally published: Feb. 24, 2021; updated: June 20, 2022]

Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.

As the COVID-19 pandemic enters its third year, the Omicron variant and its subvariant BA.2 have been driving an uptick in cases in the United States primarily among people who are unvaccinated, and it is even causing infections in some vaccinated people. The good news is that COVID-19 vaccines are still expected to be effective at preventing severe disease, hospitalization, and death from COVID-19

In the U.S., infants, children, and adults ages 6 months and older are eligible to be vaccinated, according to the Centers for Disease Control and Prevention (CDC). 

As the SARS-CoV-2 virus mutates and new variants emerge, it’s important to keep up with how well the vaccines are performing, but it’s also a daunting task, given the flood of information (and misinformation) coming at us from so many directions.

We mapped out a comparison of the most prominent COVID-19 vaccines.

The three vaccines in use in the U.S.

Pfizer-BioNTech   

The Pfizer-BioNTech vaccine (brand name: Comirnaty) was granted full Food and Drug Administration (FDA) approval in August 2021 for people ages 16 and older. Before that, it was the first COVID-19 vaccine to receive FDA Emergency Use Authorization (EUA) back in December 2020, after the company reported that its vaccine was highly effective at preventing symptomatic disease. This is a messenger RNA (mRNA) vaccine, which uses a relatively new technology. It must be stored in freezer-level temperatures, which can make it more difficult to distribute than some other vaccines.

Who can get it: Anyone ages 16 and older in the U.S. Infants, children, and teenagers ages 6 months to 15 years are eligible under an EUA. 

Dosage: For the primary series: two shots, 21 days apart. Fully effective two weeks after the second shot. Dosages for children are different than dosages for adults. For some people older than 12, especially boys and men between ages 12 and 39, the CDC suggests an eight-week interval between the two shots to reduce the risk of myocarditis, an uncommon side effect (see FDA warnings below).

Who can get the booster: Most children and teenagers ages 5 to 17 should get a Pfizer-BioNTech booster five months after completing the initial Pfizer-BioNTech primary series. Most adults should get a booster at least five months after their primary series; for this group, a Pfizer-BioNTech or Moderna mRNA booster is preferred in most situations. Adults ages 50 or older should get a second booster at least four months after the first booster.

If you are immunocompromised: Children and teenagers ages 5 to 17 should receive three Pfizer-BioNTech primary doses, including a second dose three weeks after the first, and a third dose four weeks later. Teenagers 12 and older also can get a Pfizer-BioNTech booster shot three months after completing their initial series, and a second booster four weeks after the first. Adults who are immunocompromised can choose between the three available vaccines, following a schedule similar to immunocompromised teens (depending on which vaccine they choose—Pfizer or Moderna are recommended over Johnson & Johnson). More information for imunocompromised individuals is available on the CDC website.

Possible side effects: Pain, redness, or swelling at the site where the shot was administered, and/or tiredness, headache, muscle pain, chills, fever, or nausea throughout the rest of the body. If these side effects occur, they should go away in a few days. A few side effects are serious, but rare. These include anaphylaxis, a severe reaction that is treatable with epinephrine (the drug in Epipens®).

FDA warnings: The FDA added a warning label on the mRNA vaccines regarding serious (but rare) cases of inflammation of the heart muscle (myocarditis) and of the outer lining of the heart (pericarditis) in adolescents and young adults, more often occurring after the second dose of an mRNA vaccine. The inflammation, in most cases, gets better on its own without treatment.

How it works:  It uses mRNA technology, which is a new type of vaccine. It works by sending instructions to host cells in the body for making copies of a spike protein (like the spikes you see sticking out of the coronavirus in pictures). But our cells recognize that this protein doesn’t belong, and the immune system reacts by activating immune cells and producing antibodies. This will prompt the body to recognize and attack the real SARS CoV-2 spike protein if you become exposed to the actual virus.

How well it works: When Pfizer-BioNTech applied for FDA authorization for its vaccine in December 2020, its initial Phase 3 clinical data surpassed expectations with 95% efficacy, based on an independent analysis by the FDA. But data on real-world effectiveness for adults shows that the protection from the mRNA two-dose primary series wanes over time; however, a booster dose (for those who are eligible) brings the immune system back to robust levels.

How well it works  against variants: Scientists are still learning about how effective the Pfizer-BioNTech vaccine is against Omicron, which is the predominant variant in the U.S. Early this year, the CDC published data that showed the mRNA booster shots provide significant protection against hospitalization from Omicron, and can reduce the risk of going to the emergency room or urgent care clinic. Additional data from the CDC in February suggested that mRNA booster effectiveness against hospitalization and visits to emergency room or urgent care centers wanes after about four months. Recent data from the CDC and a study (not yet peer-reviewed) from the New York State Health Department showed that protection from coronavirus infection in children 5- to 11-years old waned over time, although the vaccine continued to offer protection against hospitalization and death, even during the Omicron surge.

Moderna

The FDA granted the Moderna vaccine (brand name: Spikevax) full approval for people 18 and older in January 2022, upgrading the vaccine’s EUA, which was granted in December 2020 (a week after Pfizer-BioNTech). Moderna uses the same mRNA technology as Pfizer-BioNTech and had a similarly high efficacy at preventing symptomatic disease when the companies applied for authorization; it also needs to be stored in freezer-level temperatures. 

Who can get it: Infants, children, and adults ages 6 months and older in the U.S. 

Dosage: For the primary series: two shots, 28 days apart. Fully effective two weeks after the second shot. Dosages for children are different than dosages for adults. For some people older than 12, especially boys and men between ages 12 and 39, the CDC suggests an eight-week interval between the two shots to reduce the risk of myocarditis, an uncommon side effect (see FDA warnings below).

Who can get the booster: Anyone ages 18 or older should get a booster shot five months after their Moderna (two-shot) primary series. A Pfizer-BioNTech or Moderna mRNA booster is preferred in most situations. (Only Pfizer boosters are authorized for children and teenagers.) Adults ages 50 and older should get a second booster four months after the first. 

If you are immunocompromised: Anyone 18 and older who is moderately or severely immunocompromised should get an additional primary shot (or third dose) of the Pfizer-BioNTech or Moderna vaccine 28 days after their second Moderna shot. They will be eligible for a booster shot five months later and can choose either a Moderna or Pfizer-BioNTech booster in most cases. Adults with certain immune deficiencies should also get a second Pfizer-BioNTech or Moderna booster; immunocompromised teenagers ages 12-17 must get this booster from Pfizer. More information for immunocompromised people is available on the CDC website.

Possible side effects: The side effects are similar to Pfizer-BioNTech’s vaccine: Pain, redness, or swelling at the site where the shot was administered—and/or tiredness, headache, muscle pain, chills, fever, or nausea throughout the rest of the body. If any of these side effects occur, they should go away in a few days. A few side effects are serious, but rare. These include anaphylaxis, a severe reaction that is treatable with epinephrine (the drug in Epipens®).

FDA warnings: The FDA placed a warning label on the Moderna vaccine regarding a “likely association” with reported cases of heart inflammation in young adults. This inflammation may occur in the heart muscle (myocarditis) or in the outer lining of the heart (pericarditis)—it more often occurs after the second dose of an mRNA vaccine. The inflammation, in most cases, gets better on its own without treatment.

How it works: Similar to the Pfizer vaccine, this is an mRNA vaccine that sends the body’s cells instructions for making a spike protein that will train the immune system to recognize it. The immune system will then attack the spike protein the next time it sees one (attached to the actual SARS CoV-2 virus).

How well it works: Moderna’s initial Phase 3 clinical data in December 2020 was similar to Pfizer-BioNTech’s—at that point, both vaccines showed about 95% efficacy.

How well it works on virus variants: Scientists are still learning about how effective the Moderna vaccine is against Omicron. Early this year, the CDC has published data that showed the mRNA booster shots provided significant protection against hospitalization from Omicron, and can reduce the risk of going to the emergency room or urgent care clinic. Additional data from the CDC in February suggested that mRNA booster effectiveness against hospitalization and visits to emergency room or urgent care centers wanes after about four months.

Johnson & Johnson

The FDA authorized Johnson & Johnson’s coronavirus vaccine (brand name: Janssen) in February 2021. Unlike the first two vaccines, this is a carrier, or virus vector, vaccine, a type of vaccine that has been used before for the flu. A one-shot strategy made J&J’s vaccine easier to distribute and administer to people who found it the be the most convenient vaccine to get. But in the spring of 2021, concerns over rare blood clots associated with the vaccine prompted the government to put a pause on it, which was soon lifted. Then, in December the CDC again responded to those concerns by expressing a preference for the Pfizer and Moderna shots. In May, the FDA put new restrictions on who can get the J&J vaccine based on another review of data on the life-threatening clots.

Who can get it: Adults 18 and older who specifically request the J&J vaccine or who cannot have the other available vaccines for medical reasons.

Dosage: Single shot. Fully effective two weeks after vaccination.

Who can get the booster: In most situations, everyone ages 18 or older should get a Pfizer-BioNTech or Moderna vaccine booster dose at least 2 months after a single J&J primary shot (a J&J booster can be considered in some situations). In addition, all adults who completed a J&J primary vaccine and booster may receive a second booster from either Pfizer or Moderna.

If you are immunocompromised: If you got the single J&J shot, you should get a second shot from either Pfizer or Moderna at four weeks, and a booster two months later (Pfizer and Moderna are preferred in most situations). Immunocompromised teenagers and adults ages 12 and older can receive a 2nd booster (4th dose) of an mRNA vaccine at least four months after their first booster. 

Possible side effects: Pain, redness, swelling in the arm where the shot was administered; tiredness, headache, muscle pain, chills, fever, nausea throughout the rest of the body. If any of these side effects occur, they should go away in a few days.

FDA warnings: In July, the FDA attached a warning to the Johnson & Johnson vaccine after rare cases of the neurological disorder Guillain-Barré syndrome were reported in a small number of vaccination recipients. Most of the cases occurred within 42 days after vaccination.

In April 2021, the FDA added a warning label after ending a pause on the vaccine it had recommended “out of an abundance of caution” over an uncommon, but potentially fatal, blood clotting disorder that occurred in a small number of recipients.

In December, the FDA updated its fact sheet on the shot to include information about the rare but serious blood clotting disorder called thrombosis with thrombocytopenia syndrome (TTS) that was associated with the vaccine. In May, after another review of available data on this risk, the FDA made a decision to put restrictions on access to the J&J vaccine.

How it works: This is a carrier vaccine, which uses a different approach than the mRNA vaccines to instruct human cells to make the SARS CoV-2 spike protein. Scientists engineer a harmless adenovirus (a common virus that, when not inactivated, can cause colds, bronchitis, and other illnesses) as a shell to carry genetic code on the spike proteins to the cells (similar to a Trojan Horse). The shell and the code can’t make you sick, but once the code is inside the cells, the cells produce a spike protein to train the body’s immune system, which creates antibodies and memory cells to protect against an actual SARS-CoV-2 infection.

How well it works: The data J&J submitted to the FDA in early 2021 when it applied for authorization for its vaccine showed 67% efficacy in preventing moderate to severe/critical disease by 14 days after vaccination—and 66% effective 28 days after vaccination.

How well it works on virus variants: At the end of 2021, J&J announced that preliminary study results from South Africa showed a J&J booster to be 85% effective against hospitalization at a time when Omicron was the dominant variant in that country. More data on the vaccine’s effectiveness against Omicron is forthcoming.

Two vaccines not available in the U.S.

Novavax 

The Novavax vaccine (brand names: Nuvaxovid and Covovax) is on track to become the fourth COVID-19 vaccine in the U.S. after a committee of advisors to the FDA voted to recommend an EUA. If the vaccine is authorized, it would become available sometime after the CDC finalizes the FDA authorization. Novavax is already being used in 40 other countries, and had a 90% efficacy in its clinical trial, performing almost as well as the mRNA vaccines in their early trials. This vaccine is a protein adjuvant. It is simpler to make than some of the other vaccines and can be stored in a refrigerator, making it easier to distribute. 

Status: Novavax submitted an application to the FDA for authorization at the end of January for its primary vaccine. A committee of advisors has recommended it to the FDA, but the agency has yet to authorize it. The company is also studying the safety and effectiveness of a booster.

Who it may be recommended for: Novavax is asking for an EUA for adults 18 and older. The company is studying the vaccine in children and teenagers ages 12 to 17.

Dosage: 2 doses, 21 days apart

Possible side effects: Injection site tenderness, fatigue, headache, muscle pain. There were rare cases of myocarditis and pericarditis (six cases in 40,000 participants) in the clinical trial. 

How it works: Unlike the mRNA and vector vaccines, this is a protein adjuvant (an adjuvant is an ingredient used to strengthen the immune response). While other vaccines trick the body’s cells into creating parts of the virus that can trigger the immune system, the Novavax vaccine takes a different approach. It contains the spike protein of the coronavirus itself, but formulated as a nanoparticle, which cannot cause disease. When the vaccine is injected, this stimulates the immune system to produce antibodies and T-cell immune responses.

How well it works: 90% effective against lab-confirmed, symptomatic infection and 100% against moderate and severe disease in Phase 3 trial results published in The New England Journal of Medicine in December 2021.  

How well it works on virus variants: The data presented to the FDA was gathered before Omicron or its BA.2 subvariant started to circulate, so more information will be needed to show how well Novavax works against the variant. 

Oxford-AstraZeneca

This Oxford-AstraZeneca vaccine, which is currently being distributed in the United Kingdom and other countries, is distinguished from some of its competitors by its lower cost—it’s cheaper to make per dose, and while some of the other vaccines must be stored frozen, this one can be stored in normal refrigeration for at least six months, making it easier to distribute.

Oxford-AstraZeneca is currently studying the efficacy of a booster shoot.

Status: Not available in the U.S., authorized for emergency use in other countries, including in the European Union (under the name Vaxzevria) and the United Kingdom.

Recommended for: Adults 18 and older

Dosage: Two doses, four to 12 weeks apart

Possible side effects: Tenderness, pain, warmth, redness, itching, swelling or bruising at the injection site, all of which generally resolve within a day or two.

Rare side effects: Some countries temporarily suspended use of this vaccine in March after a small number of recipients developed blood clots and some died. In April, a European Medicines Agency (EMA) safety committee concluded "unusual blood clots with low blood platelets should be listed as very rare side effects" that could occur within two weeks of receiving the vaccine, and stressed that the benefits still outweigh the risks. In July, a study by the drugmaker, published in the Lancet, estimated the rate of thrombosis with thrombocytopenia syndrome, a clotting disorder, at 8.1 cases per million in those who received a first dose of the vaccine, and 2.3 per million after the second dose, which is comparable to incidence in the general population.

How it works: Similar to the Johnson & Johnson vaccine, this is a carrier vaccine. Scientists engineer a harmless adenovirus as a shell to carry genetic code on the spike proteins to the cells. Once the code is inside the cells, the cells produce a spike protein to train the body’s immune system, which creates antibodies and memory cells to protect against an actual SARS-CoV-2 infection.

How well it works: AstraZeneca updated its data analysis of its phase 3 trials in March 2021, showing its vaccine to be 76% effective at reducing the risk of symptomatic disease 15 days or more after receiving the two doses, and 100% against severe disease. The company also said the vaccine was 85% effective in preventing COVID-19 in people over 65.

How well it works on virus variants: Scientists are still learning about how effective the vaccine is against the Omicron variant. Researchers in Israel are testing a fourth dose of this vaccine against Omicron. 

Note: None of the COVID-19 vaccines change—or interact with—a recipient’s DNA. 

[Visit Yale Medicine's Vaccine Content Center for more stories on COVID-19 vaccines.]

Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.  

This article was reviewed by Yale Medicine infectious diseases specialist  Jaimie Meyer, MD, MS .