Immune correlates of protection against RSV following Ad26.RSV.preF–RSV preF vaccination of adults aged >60 years

Abstract Respiratory syncytial virus (RSV) is a leading cause of respiratory illness and there is no universally accepted serological correlate of protection (CoP). We evaluated serum pre-fusion immunoglobulin G binding (preF-IgG) and RSV-A2 neutralizing antibodies (RSV-nAb) in adults aged >60 years following vaccination with investigational Ad26.RSV.preF–RSV preF vaccine. PreF-IgG and RSV-nAb measured pre-vaccination (Day 1) and Day 15 post-vaccination were assessed as CoPs against RSV-mediated acute respiratory infection (ARI) and lower respiratory tract disease (LRTD). An increase in both preF-IgG and RSV-nAb at Day 15 was significantly associated with reduced occurrence of RSV-mediated ARI and LRTD during follow-up. Based on controlled vaccine-efficacy curves and Prentice criteria, both markers were identified as CoPs for RSV-mediated ARI and LRTD. These results were validated using samples from a second randomized, phase 3 efficacy trial. Comprehensive profiling of preF-specific antibody responses showed that preF IgG3 and IgG2 may also contribute to protection from RSV.