An Adjuvanted, Postfusion F Protein–Based Vaccine Did Not Prevent Respiratory Syncytial Virus Illness in Older Adults

In a randomized, placebo-controlled, phase 2b clinical trial, an adjuvanted vaccine containing the respiratory syncytial virus (RSV) fusion protein was immunogenic but did not protect older adults from disease caused by RSV. Abstract Background Respiratory syncytial virus (RSV) is an important cause of illness in older adults. This study assessed efficacy of a vaccine for prevention of RSV-associated acute respiratory illness (ARI), defined by specified symptoms with virologic confirmation. Methods This phase 2b study evaluated RSV postfusion F protein (120 µg) with glucopyranosyl lipid adjuvant (5 µg) in 2% stable emulsion. Subjects aged ≥60 years were randomly assigned at a ratio of 1:1 to receive vaccine or placebo (all received inactivated influenza vaccine). Ill subjects recorded symptoms and provided blood and nasal swab samples. Results In the per-protocol population (n = 1894), the incidence of RSV-associated ARI occurring ≥14 days after dosing was 1.7% and 1.6% in the vaccine and placebo groups, respectively, for a vaccine efficacy (VE) of –7.1% (90% confidence interval [CI], –106.9%–44.3%). Efficacy was not observed in secondary analyses that included seroresponse to nonvaccine RSV antigens (VE, 8.9%; 90% CI, –28.5%–35.4%) or symptoms combined with seroresponse (VE, 10.0%; 90% CI, –45.4%–44.4%). On day 29, 92.9% of vaccinees had an anti-F immunoglobulin G antibody seroresponse. Overall, 48.5% and 30.9% of RSV vaccine recipients reported local and systemic solicited symptoms, respectively. Conclusion The RSV vaccine was immunogenic but did not protect older adults from RSV illness. Clinical Trials Registration NCT02508194.