Every RSV vaccine approved or in late-stage development is built around the same molecular target: a stabilized version of the virus’s fusion protein, locked in its prefusion shape. The two licensed products, Arexvy and Abrysvo, deliver that protein directly as a purified ingredient. An mRNA candidate, mRNA-1345, instead delivers genetic instructions wrapped in lipid nanoparticles so your cells build the protein themselves. Beyond the active ingredient, what separates these vaccines from each other comes down to whether they include an adjuvant, whether they cover one RSV subgroup or two, and the supporting ingredients that keep everything stable in the vial.
The Prefusion F Protein
RSV uses a surface protein called the fusion (F) glycoprotein to break into human cells. Before it fuses with a cell membrane, the F protein sits in a shape researchers call the “prefusion” conformation. Once it does its job, it snaps irreversibly into a different shape known as “postfusion.” This matters because the prefusion form exposes molecular features that the immune system recognizes far more effectively. Antibodies trained against prefusion F are substantially better at neutralizing the virus than those trained against postfusion F.
The catch is that the prefusion shape is inherently unstable. Left alone, the protein tends to spring forward into its postfusion form, which would make it a poor vaccine ingredient. Researchers solved this by introducing specific mutations that lock the protein in place. One approach blocks the localized structural changes that normally trigger the large-scale rearrangement from prefusion to postfusion, essentially freezing the protein mid-stance.1PubMed. Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation This engineered, stabilized prefusion F protein is the active ingredient in both Arexvy and Abrysvo, and the protein encoded by the mRNA in Moderna’s candidate vaccine.
The F protein has several key spots where neutralizing antibodies like to bind. Two major neutralizing sites, called antigenic sites II and IV, exist on both the prefusion and postfusion forms of the protein.2PubMed Central. Neutralizing Epitopes on the Respiratory Syncytial Virus Fusion Glycoprotein But the prefusion shape also displays additional sites, sometimes referred to as site Ø and site V, that are among the most potent targets for virus-blocking antibodies. When the protein flips to postfusion, those sites disappear. This is why the entire vaccine strategy hinges on keeping the protein in its prefusion conformation: it presents the full menu of targets the immune system can learn from.
One Subgroup or Two
RSV circulates as two subgroups, RSV A and RSV B, which co-circulate each season in varying proportions. The F protein is fairly well conserved between the two subgroups, but the amino acid differences that do exist concentrate in the prefusion-specific antigenic sites, and those differences are more pronounced in RSV B.3PubMed Central. Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures In practical terms, this means a vaccine based solely on one subgroup’s F protein might protect against the other subgroup less strongly or for a shorter time.
The two licensed vaccines took different approaches to this problem. Arexvy (GSK) uses a single prefusion F protein derived from an RSV A sequence and pairs it with an adjuvant to boost the immune response. Abrysvo (Pfizer) contains stabilized prefusion F antigens from both RSV A and RSV B, making it a bivalent vaccine, but does not include an adjuvant.4Clinical Infectious Diseases. Efficacy, Immunogenicity, and Safety of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Vaccine in Older Adults Over 2 RSV Seasons Clinical data from bivalent vaccine studies show high efficacy against disease from both subgroups, while studies of the monovalent approach suggest that cross-protection against RSV B may not last as long.5PubMed Central. Adult RSV Vaccination: What Is the Role of RSV Subgroup in Disease Prevention? Each strategy has trade-offs: the bivalent vaccine covers both subgroups directly, while the monovalent vaccine compensates with an adjuvant designed to amplify the immune response.
In the Abrysvo multidose vial presentation, each dose contains 120 micrograms of the bivalent prefusion F protein.6PubMed Central. Safety and immunogenicity of bivalent RSVpreF vaccine formulated in a multidose vial in healthy female participants in the USA That protein is supplied as a freeze-dried powder and reconstituted before injection.
What the Adjuvant Does
Arexvy’s secret sauce, beyond the F protein itself, is its adjuvant system called AS01E. An adjuvant is a substance added to a vaccine specifically to strengthen the body’s immune response to the protein. Without one, a purified protein injected into the arm can sometimes produce a lackluster response, especially in older adults whose immune systems have slowed down. The adjuvant gives the immune system a sharper nudge.
A key component of AS01E is QS-21, a molecule originally derived from the bark of the Quillaja saponaria tree. QS-21 is a potent immunostimulant that promotes both antibody production and cellular immunity, working in part by activating antigen-presenting cells and stimulating pathways that help T cells mount a more focused attack.7PubMed Central. From bark to bench: innovations in QS-21 adjuvant characterization and manufacturing AS01E also contains MPL (monophosphoryl lipid A), a detoxified version of a bacterial component that triggers innate immune sensors, and liposomes that help deliver both QS-21 and MPL to the right immune cells.
Abrysvo, by contrast, contains no adjuvant. It relies on the bivalent antigen design and the inherent immunogenicity of the prefusion F protein to drive a sufficient response. This adjuvant-free profile is part of what made it suitable for approval in pregnant women, where minimizing inflammatory stimulation is a safety consideration.
How well does the adjuvanted approach work in the people who need it most? Data on Arexvy show that one month after vaccination, neutralizing antibody titers rose roughly 9- to 11-fold against RSV A and 8- to 9-fold against RSV B across different age brackets. Notably, even pre-frail and frail older adults saw comparable or even slightly higher fold-rises, suggesting the adjuvant helps overcome some of the immune sluggishness that comes with age and declining health.8Oxford Academic (Open Forum Infectious Diseases). Robust and Consistent Immune Response of the Adjuvanted Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) Across Different Age Ranges and Frailty Status in Older Adults
The mRNA Approach
Moderna’s mRNA-1345 takes a fundamentally different route to the same destination. Instead of delivering prefusion F protein directly, it delivers a strand of messenger RNA that encodes the protein. Once injected, that mRNA enters cells near the injection site, and those cells use it as a blueprint to manufacture the stabilized prefusion F protein themselves. The immune system then encounters the protein in a context that closely resembles a natural viral infection, since the protein is being produced by the body’s own cellular machinery.
The mRNA is encased in lipid nanoparticles, tiny fat-based bubbles that protect the fragile RNA strand from degradation and help it slip into cells. These nanoparticles are composed of several lipid components: an ionizable lipid that helps with cell entry, cholesterol and helper lipids that provide structural integrity, and a polyethylene glycol (PEG)-lipid coating that prevents the particles from clumping together. This is essentially the same delivery technology used in the COVID-19 mRNA vaccines, adapted for a different viral target.
Animal studies comparing lipid nanoparticle-based mRNA platforms for RSV vaccines have found that the LNP approach induces a strong cellular immune response with higher levels of Th1-type cytokines and effective neutralizing antibodies. Both LNP-delivered and alternative lipid-based platforms controlled viral load in the lungs after challenge with RSV A and RSV B strains.9International Immunopharmacology. Comparative evaluation of two platforms delivering RSV mRNA vaccines expressing modified extracellular domain of G glycoprotein in mice In human studies, revaccination with mRNA-1345 at least 12 months after an initial protein subunit RSV vaccine was well tolerated, with no safety concerns identified.10PubMed. Safety and immunogenicity of mRNA-1345 revaccination at least 12 months following primary vaccination with a licensed protein subunit RSV vaccine
Supporting Ingredients in the Vial
Beyond the active ingredient and any adjuvant, RSV vaccines contain excipients: inactive ingredients that keep the product stable, at the right pH, and in the correct physical state for injection. These are not unique to RSV vaccines and appear across many licensed vaccines.
Typical excipients in protein subunit RSV vaccines include buffers like tris(hydroxymethyl)aminomethane (Tris) to maintain pH, sodium chloride to match the salt concentration of body fluids, and sugars like sucrose or trehalose that act as stabilizers. Sucrose in particular is well established as a protectant for RSV-related biological materials, helping preserve protein structure during freeze-drying and storage.11PubMed Central. Sucrose stabilization of Respiratory Syncytial Virus (RSV) during nebulization and experimental infection Polysorbate 80, a common surfactant, may also appear to prevent protein aggregation. None of these excipients are pharmacologically active at the trace amounts present in a vaccine dose.
The mRNA vaccines have their own set of excipients related to the lipid nanoparticle system. In addition to the lipid components already described, the formulation includes buffers and cryoprotectants that keep the nanoparticles intact during frozen storage. The mRNA itself is manufactured enzymatically and purified to remove double-stranded RNA contaminants that could trigger unwanted inflammatory responses.
Why Prefusion and Not the Whole Virus
The reason every modern RSV vaccine is built around a carefully engineered protein rather than a killed or weakened virus traces back to a catastrophic clinical trial in the 1960s. Researchers at the time developed a formalin-inactivated RSV vaccine (FI-RSV) and tested it in infants. Instead of protecting the children, the vaccine primed their immune systems in a harmful way. When vaccinated children later encountered natural RSV, many developed enhanced respiratory disease far worse than what unvaccinated children experienced, and two toddlers died.
Decades of work eventually explained what went wrong. The formalin treatment denatured the virus’s proteins, pushing them into non-native conformations. The immune system generated antibodies against these malformed proteins, but those antibodies could not effectively neutralize the live virus. Worse, the vaccine triggered a lopsided immune memory dominated by a particular type of helper T cell response, which led to damaging inflammation, mucus overproduction, and immune complex deposits in the lungs when the real virus arrived.12PubMed Central. Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease Research confirmed that this skewed immune response drove the lower airway pathology and airway hypersensitivity that characterized the enhanced disease.13PLoS Pathogens. RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets
This disaster set the field back by decades, but it also shaped every design decision in today’s vaccines. The stabilized prefusion F protein generates the right kind of antibodies, ones that effectively neutralize the virus, while also stimulating a balanced T cell response rather than the harmful skew seen with FI-RSV. The use of specific adjuvants like AS01E further helps steer the immune response toward a protective pattern. Enhanced disease has not been observed with any of the modern prefusion-based RSV vaccines in clinical trials.
The Same Vaccine for Pregnant Women
Abrysvo holds a unique position: it is the only RSV vaccine approved for use in pregnant women, given during the third trimester to protect newborns through passively transferred antibodies. The vaccine itself is identical to the version given to older adults. The idea is straightforward. When a pregnant person receives the vaccine, their immune system produces high levels of antibodies against prefusion F. A specific class of these antibodies, IgG1, is selectively and actively transported across the placenta to the fetus via a receptor called FcRn.14PubMed Central. Immune Mechanisms Underlying Neonatal Protection Following Maternal RSV Vaccination
Timing matters. Antibody transfer across the placenta is not instantaneous; it takes weeks for the process to reach full efficiency. When vaccination occurred only two to three weeks before delivery, the ratio of cord blood antibodies to maternal antibodies was significantly lower than when vaccination happened more than five weeks before birth.15PubMed Central. Enhanced placental antibody transfer efficiency with longer interval between maternal respiratory syncytial virus vaccination and birth This is why the vaccine is recommended during a specific window of the third trimester rather than right before the due date.
The payoff can be substantial. Cord blood from vaccinated mothers showed neutralizing antibody levels roughly 6.5-fold higher against RSV A and about 10-fold higher against RSV B compared with cord blood from unvaccinated mothers.16Nature Communications. Maternal RSV vaccination generates high-affinity antibodies that efficiently transfer to infants, providing enhanced passive immunity How long that protection lasts in any given infant depends on several factors, including gestational age at birth, how strongly the mother responded to the vaccine, and when during RSV season the baby is born.17Journal of the Pediatric Infectious Diseases Society. New and Emerging Passive Immunization Strategies for the Prevention of RSV Infection During Infancy Preterm infants, who spend less time in utero during the peak antibody transfer window, tend to receive lower antibody levels even when their mothers are vaccinated, though the transfer efficiency itself remains consistent.
Monoclonal Antibodies Are Not Vaccines, but They Overlap
If you have heard about nirsevimab (sold as Beyfortus) in the same breath as RSV vaccines, it is worth understanding what that product actually is and how its contents differ. Nirsevimab is not a vaccine. It is a lab-made monoclonal antibody, a single pre-formed antibody that targets the same prefusion F protein the vaccines train your immune system to attack. Specifically, it binds to a conserved spot on the prefusion F surface called site Ø.18PubMed Central. Nirsevimab for respiratory syncytial virus prevention: A comprehensive product review
Because it is a ready-made antibody rather than an immune training exercise, nirsevimab provides immediate protection from a single injection. Its half-life has been engineered to be unusually long for an antibody, giving roughly a full RSV season of coverage. It is approved for all infants entering their first RSV season, regardless of risk level, and for some young children heading into their second season. Nirsevimab and maternal vaccination with Abrysvo are considered alternative strategies for protecting newborns, not complementary ones. Public health agencies generally recommend one or the other for a given infant, not both, since combining them has not been shown to add meaningful benefit and adds cost.
The contents of a nirsevimab injection are simpler than those of a vaccine. There is no antigen, no adjuvant, and no mRNA. The vial contains the purified antibody itself in a buffered solution with amino acids like histidine and L-arginine to maintain stability, along with sucrose and polysorbate 80 performing the same stabilizer and surfactant roles they play in other injectable biologics.