Two Vaccines, One Structural Breakthrough: How Abrysvo and Arexvy Work

Both Abrysvo and Arexvy are protein subunit vaccines that exploit the same foundational scientific discovery: the stabilisation of the RSV fusion (F) protein in its prefusion conformation. This structural insight, first reported in a landmark 2013 paper in Science, revealed that the prefusion form of the F protein exposes potent neutralising epitopes that the post-fusion form does not. Targeting this conformation dramatically increases the antibody response elicited by vaccination and underpins both platforms.

Despite sharing the same scientific foundation, the two products differ in meaningful ways. Pfizer’s Abrysvo is a bivalent vaccine containing prefusion-stabilised F proteins from both RSV subtype A and RSV subtype B, formulated without an adjuvant. GSK’s Arexvy, by contrast, uses a monovalent prefusion F protein antigen from RSV subtype A combined with the company’s proprietary AS01E adjuvant system — the same adjuvant platform used in its approved shingles vaccine Shingrix. The AS01E system, which contains MPL (3-O-desacyl-4′-monophosphoryl lipid A) and QS-21 (a saponin), is designed to amplify and shape the immune response, potentially compensating for the use of a single-subtype antigen.

Both vaccines are administered as a single intramuscular dose and were approved by the FDA in May–June 2023, making them the first RSV vaccines approved for adults in more than five decades of vaccine research. Their approval marked the culmination of a scientific and commercial race that accelerated sharply after the 2013 structural breakthrough.

Pivotal Trial Efficacy: What the Phase 3 Data Showed

Both vaccines demonstrated strong first-season efficacy against RSV-associated lower respiratory tract disease (LRTD) in their respective Phase 3 pivotal trials, though direct head-to-head comparisons are not available and trial designs differed in ways that make numerical comparisons difficult. GSK’s AReSVi-006 trial and Pfizer’s RENOIR trial each enrolled tens of thousands of adults aged 60 and older across multiple countries and RSV seasons.

In the AReSVi-006 trial, Arexvy demonstrated approximately 82.6% efficacy against RSV-associated LRTD with at least two signs or symptoms, and approximately 94.1% efficacy against RSV-associated LRTD with at least three signs or symptoms in the first season. In the RENOIR trial, Abrysvo demonstrated approximately 66.7% efficacy against RSV-associated LRTD in adults 60 and older. Both trials also showed meaningful reductions in RSV-associated acute respiratory illness and, critically, demonstrated protection against severe lower respiratory tract disease — the outcome most relevant for preventing hospitalisation in older adults.

“Direct head-to-head comparisons between Abrysvo and Arexvy do not exist — differences in trial design, endpoint definitions, and RSV season timing mean that cross-trial efficacy numbers must be interpreted with significant caution.”

It is essential to note that the apparent numerical difference in first-season efficacy between the two vaccines cannot be used to conclude that one is superior to the other. The trials enrolled different populations, were conducted across different RSV seasons with differing circulating strain compositions, used different case definitions, and measured outcomes at different time points. According to guidance from WHO, indirect comparisons of vaccine efficacy across trials must account for these methodological differences before drawing any conclusions.

Durability and Waning Immunity: The Long-Term Efficacy Question

The most consequential unanswered question for both Abrysvo and Arexvy is how well protection persists beyond the first RSV season. Waning immunity is a known challenge for many respiratory virus vaccines, and RSV vaccines for older adults are no exception — particularly given the immunosenescence (age-related decline in immune function) that affects the very population these vaccines are designed to protect.

Second-season data from both pivotal trials has been published and shows, as expected, some degree of waning protection. For Arexvy, GSK has reported that efficacy against RSV-LRTD remained statistically significant into the second season, though point estimates were lower than in the first season. For Abrysvo, Pfizer has similarly reported continued but attenuated protection in the second year of follow-up. The precise magnitude of waning differs between the two products, and again, cross-trial comparisons must be made cautiously.

A critical consideration is whether waning efficacy against symptomatic RSV-LRTD translates into waning protection against the most severe outcomes — hospitalisation and death. Preliminary data from both trials and early real-world studies suggest that protection against severe disease may be more durable than protection against milder symptomatic illness, a pattern observed with other respiratory virus vaccines. This distinction matters clinically: even a vaccine with substantially waned efficacy against mild RSV-LRTD may still provide meaningful protection against the outcomes that drive healthcare utilisation and mortality in older adults.

Real-World Effectiveness: Evidence from the 2023–2024 RSV Season

Real-world effectiveness (RWE) data from the first RSV season following the 2023 approvals provides an important complement to pivotal trial results, capturing the performance of both vaccines across the diverse older adult population in routine clinical practice rather than the controlled conditions of a randomised trial.

Observational studies and surveillance data from the 2023–2024 RSV season, including analyses published through the CDC‘s Influenza and Other Viruses in the Acutely Ill (IVY) Network and similar platforms in Europe, have generally confirmed meaningful protection against RSV-associated hospitalisation in adults 60 and older who received either vaccine. These studies face inherent methodological limitations — including healthy vaccinee bias, potential confounding by indication, and the challenge of ascertaining RSV vaccination status in medical records — but their overall direction is consistent with pivotal trial findings.

An important nuance in interpreting real-world data is that many studies in the first season could not separately analyse Abrysvo and Arexvy recipients due to limited sample sizes for each product. As uptake grows and multiple seasons of data accumulate, more granular product-specific real-world effectiveness estimates are expected to emerge. The PatSnap Life Sciences platform allows researchers and pharmaceutical teams to track publication activity and regulatory submissions related to RSV vaccine effectiveness as the evidence base develops.

A further consideration for real-world interpretation is population heterogeneity. Older adults with underlying cardiopulmonary disease, immunocompromising conditions, or frailty may respond differently to vaccination than the healthier trial populations. Both manufacturers have conducted or are conducting analyses in higher-risk subgroups, and regulatory agencies are monitoring these data as part of their post-marketing commitments. The CDC’s ACIP has noted that individuals with underlying conditions associated with high risk of severe RSV disease may derive the greatest benefit from vaccination, supporting targeted use even in the context of shared clinical decision-making guidance.

Patent Landscape: The IP Battle Behind the RSV Vaccine Race

The commercial success of Abrysvo and Arexvy rests not only on clinical efficacy but on extensive and contested intellectual property portfolios that shape competitive dynamics, licensing opportunities, and the prospects for next-generation RSV vaccines. Understanding this patent landscape is essential for pharmaceutical companies, biotech firms, and investors navigating the RSV space.

The foundational patents covering prefusion-stabilised RSV F proteins trace back to work conducted at the National Institutes of Health (NIH) and subsequently licensed to multiple vaccine developers. The NIH’s Vaccine Research Center, led by Barney Graham and Jason McLellan, filed key patents covering the DS-Cav1 prefusion-stabilised F protein design — a series of mutations that lock the F protein in its prefusion conformation. These patents, licensed to multiple parties, have been central to patent disputes and licensing negotiations across the RSV vaccine industry, as documented in filings tracked by WIPO.

Beyond the foundational antigen patents, both Pfizer and GSK have built layered patent portfolios covering formulation, manufacturing processes, adjuvant compositions (in GSK’s case), and combination vaccine approaches. GSK’s AS01E adjuvant system is itself protected by an extensive patent estate that creates a significant barrier to replication by competitors. Pfizer’s bivalent approach — covering both RSV-A and RSV-B F proteins — is similarly protected by composition-of-matter and method-of-use patents.

The RSV vaccine patent landscape is also evolving rapidly as new entrants — including mRNA-based RSV vaccines and combination RSV/influenza products — advance through clinical development. Patent filings in the RSV space have accelerated since 2013, with activity from established vaccine manufacturers, mRNA platform companies, and academic institutions. Monitoring this activity through platforms such as PatSnap allows R&D and IP teams to anticipate competitive moves, identify white-space opportunities, and manage portfolio risk as the market matures.

For pharmaceutical companies considering entry into the RSV vaccine market — whether through novel antigens, adjuvant systems, delivery platforms, or combination products — a thorough freedom-to-operate analysis covering the NIH foundational patents, the Pfizer and GSK portfolios, and the growing body of academic and biotech filings is essential. PatSnap Eureka’s AI-powered patent search and analysis capabilities are purpose-built for this type of landscape mapping.