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

In its recommendations for COVID vaccines, the CDC has cited a study showing the risk of cardiac complications, including myocarditis (an inflammation of the heart muscle), in males 12-17 years old was 1.8–5.6 times higher after a COVID infection compared to after COVID vaccination.

In December 2020, Pfizer-BioNTech’s Phase 3 clinical data for its original vaccine showed 95% efficacy for preventing symptomatic COVID. Later data on real-world effectiveness for adults showed that the protection from the mRNA two-dose primary series waned over time, suggesting that updated vaccines would be needed to bring the immune system back to robust levels.

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.

Status: Moderna’s vaccine has been updated over time to target new virus variants. First introduced in December 2020, the original COVID mRNA vaccines from both Pfizer and Moderna protected against the original SARS-CoV-2 virus. They have been replaced three times since then with shots targeting different iterations of the Omicron strain. In 2022, “bivalent” vaccines targeted both the original virus and Omicron variants BA.4 and BA.5; in 2023, a monovalent shot targeted the XBB lineage of the Omicron variant; and in 2024, a new updated shot aims to protect against KP.2, which circulated in the U.S. earlier in the year. The previous vaccines are no longer in use.

Who can get it: People ages 6 months and older. The CDC has specific recommendations for the following groups, noting that anyone who recently had COVID may need to consider delaying their vaccination by 3 months:

• Children ages 6 months to 4 years need multiple doses (check the CDC website for more specific recommendations), including at least one dose of the 2024-2025 updated vaccine.

• Children ages 5 to 11 years may get one dose of the 2024-2025 updated vaccine.

• People ages 12 and older may get one dose of the 2024-2025 updated vaccine.

For adults ages 65 years and older, an additional COVID-19 vaccine dose—beyond what is listed here—is NOT currently recommended unless they are moderately or severely immunocompromised.

For people who are moderately or severely immunocompromised: Different recommendations can be found on the CDC website.

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 host cells in the body 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: The 2024-2025 updated vaccines were approved based on preclinical studies of their efficacy against the latest circulating strains. Some people may still become infected even though they have been vaccinated, but the goal of the vaccines now is to prevent severe disease, hospitalization, and death. Research has suggested that people who are infected after vaccination also are less likely to report Long COVID compared to those who were not vaccinated.

In its recommendations for COVID vaccines, the CDC has cited a study showing the risk of cardiac complications, including myocarditis (an inflammation of the heart muscle), in males 12-17 years old was 1.8–5.6 times higher after a COVID infection compared to after COVID vaccination.

Moderna’s initial Phase 3 clinical data in December 2020 was similar to Pfizer-BioNTech’s—both vaccines showed about 95% efficacy for prevention of COVID. Later data on real-world effectiveness for adults showed that the protection from the mRNA two-dose primary series wanes over time, but booster doses brought the immune system back to robust levels.

Novavax

The Novavax vaccine (brand names: Nuvaxovid and Covovax) was the fourth COVID vaccine to be administered in the U.S (after Johnson & Johnson, which is no longer available). The Novavax vaccine is the only non-mRNA updated COVID vaccine that has been available in the U.S. This vaccine is a protein adjuvant that had a 90% efficacy in its clinical trial, performing almost as well as the mRNA vaccines in their early trials. It is simpler to make than some of the other vaccines and can be stored in a refrigerator, making it easier to distribute.

Status: An updated 2024-2025 COVID vaccine from Novavax for children and adults ages 12 and older is not FDA-approved at this point. Novavax designed its updated shot to target JN.1, a predecessor of KP.2. Novavax’s 2023–2024 vaccine remains authorized but is no longer available in the United States, since all doses have expired, according to the CDC.