Immunogenicity and safety of different dose levels of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 years and older: A randomized, double-blind, placebo-controlled, phase 2a study.

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe illness in older adults. A combination vaccine containing Ad26.RSV.preF and purified recombinant RSV preF protein has previously demonstrated efficacy and tolerability in older adults. We report results of a dose-ranging study to determine immunogenicity and safety of different doses of the Ad26.RSV.preF component in the combined Ad26.RSV.preF/RSV preF protein vaccine to support Ad26.RSV.preF drug product release and stability specifications. METHODS: In this randomized, double-blind, placebo-controlled, phase 2a study, adults aged ≥60 years in good or stable health were randomly assigned within 1 of 3 cohorts to receive either placebo or Ad26.RSV.preF/RSV preF protein, composed of different doses of Ad26.RSV.preF with a fixed dose of RSV preF protein (150 µg). Ad26.RSV.preF doses in Cohort 1 (4 dose-down groups) ranged from 3.7 × 109 to 1.0 × 1011 viral particles (vp). Doses in Cohorts 2 and 3 (2 dose-up groups, each) ranged from 1.0 to 1.6 × 1011 vp. Primary endpoints were immunogenicity (RSV preF protein antibody titers) for Cohort 1 and safety (solicited local and systemic adverse events [AEs] and unsolicited AEs) for Cohorts 2 and 3. Immunogenicity analyses (RSV preF protein antibody titers, RSV A2 neutralizing antibodies, and RSV-F-specific interferon-γ enzyme-linked immunosorbent spot) were performed on the day of vaccination and 14 days, 3 months, and 6 months postvaccination. Safety was monitored from vaccination until study end. RESULTS: Overall, 454 participants were enrolled and received 1 dose of study vaccine or placebo (Cohort 1, n = 226; Cohort 2, n = 124; Cohort 3, n = 104). No substantial differences in measured immune responses were observed between lower or higher Ad26.RSV.preF doses compared with Ad26.RSV.preF 1.0 × 1011 vp across all postvaccination time points. All Ad26.RSV.preF doses between 3.7 × 109 vp and 1.6 × 1011 vp were well tolerated, with no safety issues identified. CONCLUSIONS: Results of this dose-ranging study may be used to inform the refinement of Ad26.RSV.preF drug product release and stability specifications. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT04453202.