The RSV vaccines approved in the United States use two different technologies: protein subunit and mRNA. The two protein subunit vaccines, Arexvy (GSK) and Abrysvo (Pfizer), were approved first in 2023. Moderna’s mRESVIA, an mRNA vaccine, followed as the third option. All three target the same part of the virus, but they get your immune system’s attention in different ways.
Protein Subunit Vaccines: Arexvy and Abrysvo
Most people receiving an RSV vaccine today will get a protein subunit shot. This is one of the oldest and most straightforward vaccine technologies. Instead of using a live or weakened virus, these vaccines contain a purified piece of the RSV virus, specifically a protein found on its surface called the fusion protein, or F protein. Your immune system recognizes this protein as foreign, mounts a response, and builds memory so it can fight the real virus later.
What makes these vaccines effective is which version of the F protein they use. The RSV fusion protein changes shape during infection. Before it attaches to a cell, it sits in a “prefusion” form. After it fuses with a cell, it flips into a different “postfusion” shape. Research showed that antibodies targeting the prefusion form are far more potent at neutralizing the virus. Both Arexvy and Abrysvo use a stabilized version of the prefusion F protein, locking it in the shape that produces the strongest immune response. A single dose generates a diverse wave of antibodies that recognize multiple vulnerable spots on the virus.
Arexvy includes an additional component called an adjuvant, a substance that amplifies the immune response. Its adjuvant system contains two immune-stimulating compounds embedded in tiny fat particles called liposomes. This combination triggers a rapid burst of immune activity within 24 hours of vaccination, leading to stronger antibody production and better immune memory. The same adjuvant technology is used in GSK’s shingles vaccine. It is particularly useful for older adults whose immune systems may not respond as vigorously on their own. Abrysvo does not contain an adjuvant.
mRNA Vaccine: mRESVIA
Moderna’s mRESVIA uses mRNA technology, the same platform behind the company’s COVID-19 vaccine. Rather than delivering the prefusion F protein directly, it delivers a strip of genetic instructions (messenger RNA) wrapped in a lipid nanoparticle. Once injected, your cells read those instructions, build copies of the prefusion F protein themselves, and display them for the immune system to learn from. The mRNA breaks down naturally within days and never enters the cell’s nucleus or alters your DNA.
The end result is similar: your body produces antibodies against the prefusion F protein. The difference is in the delivery method. Because your own cells manufacture the protein, the immune system may encounter it in a way that closely mimics a natural infection, though all three vaccines ultimately train the body to recognize the same target.
How Well Each Type Works
All three vaccines showed strong protection in clinical trials among older adults during their first season after vaccination. Arexvy demonstrated 94.1% efficacy against severe RSV-related lower respiratory tract disease. Abrysvo showed 85.7% efficacy against RSV illness with at least three symptoms. mRESVIA came in at 83.7% efficacy against RSV disease with at least two symptoms. These numbers come from slightly different trial designs, so direct head-to-head comparisons aren’t perfect, but all three clearly reduced serious illness.
Who Gets Which Vaccine
The CDC recommends a single dose of RSV vaccine for all adults 75 and older, and for adults 50 to 74 who have conditions that raise their risk of severe RSV illness. That includes chronic heart or lung disease, diabetes with organ damage, severe obesity (BMI of 40 or higher), moderate to severe immune compromise, chronic liver or kidney disease, neurologic conditions that weaken breathing muscles, and residence in a nursing home.
Abrysvo has a unique additional use: it is the only RSV vaccine approved for pregnant women. Given as a single dose during weeks 32 through 36 of pregnancy, between September and January, it allows the mother to build antibodies that cross the placenta and protect the baby from birth through their first RSV season. Babies are typically born one to two months after vaccination and have immediate protection.
RSV Vaccines vs. Monoclonal Antibodies for Infants
If you’ve heard of nirsevimab (Beyfortus) for babies, it’s worth knowing that this is not a vaccine. It’s a monoclonal antibody, a lab-made version of a single protective antibody injected directly into the infant. It provides immediate, temporary protection rather than training the baby’s own immune system. Infants whose mothers received the RSV vaccine during pregnancy generally do not need nirsevimab, since they already carry protective antibodies passed from the mother. It is recommended for babies whose mothers were not vaccinated or whose vaccination status is unknown.
Safety Signals to Know About
Common side effects of all three RSV vaccines are typical for any shot: soreness at the injection site, fatigue, headache, and muscle pain. These generally resolve within a few days.
A more serious but rare concern has emerged with the two protein subunit vaccines. The FDA now requires a warning on the prescribing information for both Arexvy and Abrysvo regarding a possible increased risk of Guillain-Barré syndrome (GBS), a nerve disorder that can cause muscle weakness, within 42 days of vaccination. Postmarketing data estimated roughly 7 excess cases per million doses of Arexvy and 9 excess cases per million doses of Abrysvo in people 65 and older. The FDA notes that while the evidence suggests an increased risk, it is not yet sufficient to confirm a direct causal link. This risk is part of why the current recommendation targets people at highest risk of severe RSV, where the benefit of vaccination is clearest.