No single RSV vaccine has proven clearly superior to the others in head-to-head trials, because no such trial exists. Three vaccines are FDA-approved for adults: GSK’s Arexvy, Pfizer’s Abrysvo, and Moderna’s mRESVIA. All three target the same viral protein in its prefusion shape, and pooled data from their clinical trials show similar overall efficacy. The differences that do exist come down to vaccine technology, how broad their coverage is, and early safety signals worth knowing about.
How the Three Vaccines Work
All three vaccines train your immune system to recognize the fusion protein on the surface of RSV, locked into the shape it takes before it enters your cells. That prefusion shape is the most effective target for generating protective antibodies. The difference is how each vaccine delivers it.
Arexvy (GSK) and Abrysvo (Pfizer) are protein-based vaccines, meaning they contain a lab-made version of the viral protein itself. mRESVIA (Moderna) is an mRNA vaccine, similar in concept to the mRNA COVID-19 vaccines: it delivers genetic instructions so your cells temporarily produce the protein on their own.
There’s also a coverage difference. Arexvy and mRESVIA each contain the fusion protein from only one RSV subtype (RSV A). Abrysvo includes fusion proteins from both RSV A and RSV B subtypes, making it a bivalent vaccine. In theory, covering both subtypes could offer broader protection, but clinical trial results haven’t shown a meaningful efficacy gap between the bivalent and single-subtype approaches so far.
Efficacy Numbers Are Similar
Because the three vaccines were tested in separate trials with different designs and populations, their efficacy numbers can’t be directly compared. However, pooled data from the GSK and Pfizer phase 3 trials, analyzed together by the CDC, gives a useful picture. Among adults 75 and older, vaccination reduced RSV-related lower respiratory tract disease by about 69% compared to placebo. Among adults 60 to 74 with risk factors for severe illness, efficacy was roughly 73%.
These pooled figures reflect high-certainty evidence, and neither vaccine consistently outperformed the other across age groups in the available data. Moderna’s mRESVIA showed comparable efficacy in its own trials, though it entered the market later and has less long-term follow-up.
How Long Protection Lasts
The most detailed durability data comes from Arexvy’s two-season trial. A single dose provided 82.6% efficacy against lower respiratory tract disease through the first RSV season, but that number gradually declined: 78.9% at one year, 77.3% by mid-second season, and 67.2% over two full seasons (a median follow-up of about 18 months). Protection against severe disease held up better, at 78.8% across both seasons.
One surprising finding: getting a second dose of Arexvy one year after the first did not improve efficacy over just the single dose. The two-dose group showed 67.1% protection against lower respiratory tract disease over two seasons, nearly identical to the single-dose group. Revaccination was well tolerated but didn’t seem to add a measurable benefit.
The CDC currently recommends only a single dose for eligible adults, regardless of which vaccine you receive. Long-term data on Abrysvo and mRESVIA durability is still accumulating.
The Safety Signal That Matters
The most significant safety concern across RSV vaccines is a rare neurological condition called Guillain-Barré syndrome (GBS), in which the immune system attacks nerve cells, causing weakness and sometimes temporary paralysis. A small increase in GBS risk has been observed after RSV vaccination.
An analysis from England estimated about 23 GBS cases per million RSV vaccine doses, with vaccinated individuals roughly 3.3 times more likely to develop GBS than expected. But the two protein-based vaccines may not carry equal risk. A U.S. analysis of 4.7 million vaccinated adults found 18.2 GBS cases per million doses of Abrysvo compared to 5.2 cases per million doses of Arexvy. A separate FDA analysis of 3.2 million Medicare recipients, however, did not find a statistically significant difference between the two products.
These are very small absolute numbers either way. For context, even the higher estimate means roughly 1 in 55,000 doses might be associated with a GBS case. But if you have a history of GBS or are weighing the vaccines against each other, this early signal favoring Arexvy on GBS risk is worth discussing with your provider.
Common, mild side effects like injection site pain, fatigue, and muscle aches are reported at similar rates across all three vaccines.
Who Should Get an RSV Vaccine
The CDC recommends RSV vaccination for all adults 75 and older, and for adults 50 to 74 who have increased risk of severe RSV illness. Risk factors include chronic heart or lung disease, a weakened immune system, other serious underlying conditions, and living in a nursing home.
You can receive an RSV vaccine at the same visit as your flu and COVID-19 vaccines. Clinical trials confirmed this is safe, though some people prefer to space them out. There’s no required waiting period between any of these vaccines.
Which One to Choose
Given the lack of a head-to-head trial, no definitive winner exists. Here’s what the available evidence suggests for practical decision-making:
- Arexvy (GSK): Has the most long-term efficacy data (two full seasons). The early GBS signal, while not conclusive, appears lower than Abrysvo’s in one large U.S. analysis. Protein-based, single subtype.
- Abrysvo (Pfizer): The only bivalent option, covering both RSV A and B subtypes. Also protein-based. Carries a potentially higher GBS signal in early surveillance, though this hasn’t been confirmed across all analyses. Also approved for use in pregnant women to protect newborns.
- mRESVIA (Moderna): The only mRNA option. May appeal to people who responded well to mRNA COVID vaccines or whose providers stock it. Has the least real-world safety and durability data of the three.
For most adults in the recommended age and risk groups, the best RSV vaccine is the one available to you. The efficacy differences between them are modest at best, and all three represent a significant reduction in the risk of serious RSV illness. If you have specific concerns about GBS or want bivalent coverage, those factors can help narrow the choice.