No single COVID vaccine is clearly “better” than the others. The three vaccines available in the United States for the 2024–2025 season, made by Moderna, Pfizer, and Novavax, all reduce the risk of hospitalization by a similar margin. Where they differ is in how they work, how they feel after injection, and which option fits best depending on your age and health status.
How Well Each Vaccine Works Right Now
All three vaccines were updated for the 2024–2025 season to target newer Omicron subvariants. Moderna and Pfizer formulated theirs around the KP.2 strain, while Novavax based its update on the closely related JN.1 strain. CDC data from September 2024 through January 2025 shows that the updated vaccines reduced COVID-related hospitalizations by about 45% in adults 65 and older without immune-compromising conditions, measured roughly two months after vaccination. For older adults with weakened immune systems, that protection was around 40%.
Those numbers don’t distinguish between brands because hospitalization rates were too low during the study period to break results out by manufacturer. That’s actually useful information in itself: the vaccines perform in a similar enough range that the CDC doesn’t recommend one over another for most people. Hospitalization rates were also low enough that researchers couldn’t calculate effectiveness against death or ICU admission separately.
How the Vaccines Differ Under the Hood
Moderna and Pfizer are both mRNA vaccines. They deliver genetic instructions that tell your cells to make a piece of the spike protein found on the surface of the virus. Your immune system then recognizes that protein as foreign and mounts a response. This process activates two major branches of your immune system: the antibody-producing side and the cell-killing side, which hunts down infected cells directly. That dual activation is a notable strength of the mRNA approach.
Novavax works differently. It’s a protein-based vaccine, meaning it delivers a pre-made version of the spike protein along with an ingredient that boosts your immune response. Your body still produces strong antibodies, but the cell-killing immune response tends to be less robust compared to mRNA vaccines. Research comparing the two approaches in animal models found that mRNA vaccines triggered significantly more memory T cells (the immune cells responsible for long-term cellular defense) and those cells were more active in producing signals that fight infection.
For most healthy people, this difference may not meaningfully change real-world protection against severe illness. But for people with weakened immune systems, the broader immune activation from mRNA vaccines could matter.
Side Effects: What to Expect
Side effects vary more by vaccine type than most people realize. mRNA vaccines (Moderna and Pfizer) tend to cause more injection site pain, reported by about 77% of recipients in one large study of healthcare workers. Protein-based and viral vector vaccines caused injection site soreness at a somewhat lower rate of around 69%.
The bigger gap shows up with whole-body symptoms. Fever after an mRNA vaccine occurred in roughly 10% of recipients, while headache and fatigue hit about 48%. Muscle pain affected around 28%, and joint pain about 14%. Novavax, being a protein-based vaccine, generally falls somewhere in between mRNA and older viral vector vaccines in terms of systemic side effects, with many recipients reporting a milder post-vaccination experience.
If you’ve had a rough time with side effects from mRNA shots in the past, Novavax offers a meaningfully different experience for many people. That’s one of the practical reasons it remains available as an option.
Myocarditis Risk by Age and Sex
Heart inflammation (myocarditis) emerged as a rare side effect of mRNA vaccines, particularly in younger males after the second dose. Among 18- to 29-year-olds in the U.S., there were an estimated 22.4 excess cases per million second doses of Pfizer and 31.2 per million second doses of Moderna. The risk is heavily concentrated in young men: males aged 16 to 17 had a reporting rate of about 76 per million after their second Pfizer dose, while females in the same age group had a rate of roughly 8 per million.
The risk drops sharply with age. For men 30 to 39, the rate fell to about 7.5 per million after dose two. For those 50 and older, it was below 1 per million. Booster doses also carried lower rates than the initial second dose across all age groups. Nearly all vaccine-associated myocarditis cases resolved with standard treatment, and the condition was typically mild compared to myocarditis caused by COVID infection itself.
Novavax has not shown the same signal for myocarditis in post-authorization surveillance, which makes it a reasonable alternative for younger men who are concerned about this specific risk.
How Quickly Protection Fades
Antibody levels decline after any COVID vaccine, but the timeline is fairly consistent across platforms. Studies of Pfizer recipients found that antibodies targeting the virus’s key binding site dropped roughly 16-fold over six months. Moderna showed a similar pattern: a 10-fold decline in binding antibodies and a 5-fold decline in virus-neutralizing antibodies over the same period, though nearly all participants still had detectable neutralizing antibodies at the six-month mark.
This waning is why updated doses are recommended annually, and why certain groups are advised to get more than one dose per season. The protection doesn’t vanish, but it weakens enough that a fresh dose provides a meaningful boost, particularly against hospitalization.
Recommendations for Older Adults and Immunocompromised People
The CDC’s Advisory Committee on Immunization Practices recommends that everyone 65 and older receive two doses of the 2024–2025 vaccine, spaced six months apart (with a minimum of two months between them). If you’re 65 or older and getting Novavax as your first-ever COVID vaccine, you’ll need a two-dose initial series followed by a third dose six months later.
People aged 6 months through 64 with moderate or severe immune compromise are also recommended to receive at least two doses of the current season’s vaccine. Based on discussion with a healthcare provider, some immunocompromised individuals may receive three or more doses in a single season. The data on seroconversion (whether the body produces a measurable antibody response) in immunocompromised patients showed similar rates between mRNA and non-mRNA vaccines, though the vast majority of studies focused on mRNA shots, making direct comparisons limited.
If You’ve Already Had COVID
Having had a previous COVID infection combined with vaccination, sometimes called hybrid immunity, provides the strongest measured protection. One large observational study found that people with a prior infection plus two doses of the Pfizer vaccine had 97.4% effectiveness against the Beta variant and 94.5% against Delta. Adding a third dose pushed effectiveness against Delta to 98.1%.
Hybrid immunity consistently outperformed either natural infection alone or vaccination alone, regardless of which variant was circulating or which mRNA vaccine was used. If you’ve had COVID before, getting vaccinated still adds a substantial and measurable layer of protection.
Vaccines for Young Children
For children under 5, Pfizer is given as a three-dose series at 3 micrograms per dose, a fraction of the 30-microgram adult dose. That lower dose was chosen because it produced immune responses comparable to older age groups while causing less fever. In clinical trials, the three-dose series was 73.2% effective against symptomatic COVID during the Omicron wave, measured from seven days after the third dose. Moderna’s pediatric vaccine uses a 25-microgram dose for young children in a two-dose series. Both are considered safe and effective for this age group.
Which One Should You Choose
For most people, the best vaccine is whichever one you’ll actually get. The protection against hospitalization is comparable across all three. If you’re a younger male concerned about the small myocarditis risk, Novavax is a reasonable choice. If you want the broadest possible immune activation, particularly if you’re immunocompromised, mRNA vaccines have the edge in stimulating both antibody and cellular responses. If you’ve had unpleasant side effects from mRNA shots before, switching to Novavax often means a milder experience. And if you’re 65 or older, the most important thing isn’t which brand you pick but making sure you get both recommended doses this season.