E.E. Walsh, G. Pérez Marc, A.M. Zareba, A.R. Falsey, Q. Jiang, M. Patton, F.P. Polack, C. Llapur, P.A. Doreski, K. Ilangovan, M. Rämet, Y. Fukushima, N. Hussen, L.J. Bont, J. Cardona, E. DeHaan, G. Castillo Villa, M. Ingilizova, D. Eiras, T. Mikati, R.N. Shah, K. Schneider, D. Cooper, K. Koury, M.-M. Lino, A.S. Anderson, K.U. Jansen, K.A. Swanson, A. Gurtman, W.C. Gruber, B. Schmoele-Thoma
5 min
Respiratory syncytial virus (RSV) poses a significant health risk to older adults, often leading to severe respiratory illness, hospitalization, and mortality. Despite decades of research, no vaccine had been successfully licensed for this population. This phase 3 trial, known as RENOIR, aimed to evaluate the efficacy and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in adults aged 60 and older.
Researchers conducted a multicenter, double-blind, randomized, placebo-controlled trial involving over 34,000 participants. Participants were assigned in a 1:1 ratio to receive either a single 120-μg dose of the RSVpreF vaccine or a placebo. The primary endpoints were vaccine efficacy against RSV-associated lower respiratory tract illness (LRTI) defined by at least two or at least three signs or symptoms. The study also monitored safety through the reporting of adverse events and reactogenicity.
The vaccine met its primary efficacy endpoints during the first RSV season. Against LRTI with at least two symptoms, the vaccine showed 66.7% efficacy. Against more severe LRTI, defined by at least three symptoms, the efficacy was 85.7%. The vaccine also demonstrated 62.1% efficacy against RSV-associated acute respiratory illness. Safety data indicated that the vaccine had an acceptable profile; while local reactions were slightly more common in the vaccine group compared to the placebo group, systemic events were similar, and no significant safety concerns were identified.
This study provides evidence for a viable vaccine strategy to protect older adults from RSV. By targeting the prefusion form of the F protein, the vaccine successfully overcomes previous challenges related to poor immunogenicity in older populations. These results suggest that vaccination could substantially reduce the burden of RSV-related morbidity in older adults, potentially decreasing hospitalizations and severe respiratory complications.
BACKGROUND: Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown. METHODS: In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 μg (RSV subgroups A and B, 60 μg each) or placebo. The two primary end points were vaccine efficacy against seasonal RSV-associated lower respiratory tract illness with at least two or at least three signs or symptoms. The secondary end point was vaccine efficacy against RSV-associated acute respiratory illness. RESULTS: At the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 cases per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date. CONCLUSIONS: RSVpreF vaccine prevented RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (≥60 years of age), without evident safety concerns. (Funded by Pfizer; RENOIR ClinicalTrials.gov number, NCT05035212; EudraCT number, 2021-003693-31.).
Alex: The systemic event profile was comparable to placebo, which is reassuring. Local injection-site reactions were modestly elevated in the vaccine arm, but that's a typical pattern. Critically, there were no signals of enhanced respiratory disease — the historical concern that derailed earlier formalin-inactivated RSV candidates in the 1960s. So the platform clears the safety bar that tripped up previous attempts.
Sam: But you said this is interim data — how much weight can we actually put on these efficacy numbers?
Alex: That's the critical caveat. Case counts for the hardest endpoints — hospitalization, ICU admission — are still too sparse to support definitive conclusions. The 85% figure is against a symptom-defined endpoint, not a hospitalization endpoint. Those are related, but they're not the same thing, and a careful referee would push back hard on conflating them.
Sam: And there's a population generalizability issue too, right? Immunocompromised patients were excluded.
Alex: That's a significant gap. The people most likely to progress to severe RSV disease — transplant recipients, patients on immunosuppressive therapy, those with haematological malignancies — are precisely the group not represented here. Extrapolating these efficacy estimates to that subpopulation requires real caution.
Sam: So durability and high-risk subgroup performance are both still open questions.
Alex: They are. Waning immunity in older adults is well-documented — we've seen it with influenza, and there's no reason to assume RSV will be different. Whether a single dose maintains protection across multiple RSV seasons, or whether this becomes an annual or biennial regimen, is something only post-licensure surveillance will answer.
Sam: Given all that, how do you read the overall significance of the RENOIR data?
Alex: The prefusion F stabilization strategy has now demonstrated meaningful efficacy in a large, well-powered phase 3 trial in a genuinely difficult population. That resolves a mechanistic question that blocked the field for decades. But the interim framing means we're reading the first chapter. Durability, real-world effectiveness in immunocompromised patients, and impact on hard endpoints like hospitalization — those are the chapters that will determine whether this vaccine actually shifts how we manage winter respiratory burden in the elderly.
Sam: A meaningful proof of concept, with the harder questions still ahead.
Alex: That's a fair summary. The platform works. Whether it works well enough, for long enough, in the patients who need it most — that's what the next few years of surveillance will tell us. Thanks for listening to ResearchPod.