Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study

作者：Beate Schmöele-Thoma, Agnieszka Zareba, Qin Jiang, Mohan S. Maddur, Rana Danaf, Alex Mann, Kingsley Eze, Juin Fok‐Seang, Golam Kabir, Andrew Catchpole, Daniel A. Scott, Alejandra Gurtman, Kathrin U. Jansen, William C. Gruber, Philip R. Dormitzer, Kena A. Swanson · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2116154 · 被引用次数：146 · 研究领域：Respiratory viral infections research、Virology and Viral Diseases、Cystic Fibrosis Research Advances

BACKGROUND: Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. METHODS: In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety. RESULTS: copies per milliliter) as measured by RT-qPCR assay was 0.0 (interquartile range, 0.0 to 19.0) in the vaccine group and 96.7 (interquartile range, 0.0 to 675.3) in the placebo group. The geometric mean factor increase from baseline in RSV A-neutralizing titers 28 days after injection was 20.5 (95% CI, 16.6 to 25.3) in the vaccine group and 1.1 (95% CI, 0.9 to 1.3) in the placebo group. More loca...