A Phase 1/2a Study Evaluating Safety and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers Aged 12-24 Months

Abstract

Respiratory syncytial virus (RSV) causes serious illness in children. The Ad26.RSV.preF vaccine candidate was immunogenic with acceptable safety in a phase 1/2a study of RSV-seropositive children. Here, we assessed its safety and immunogenicity in RSV-seronegative children. In this randomized, observer-blinded, placebo-controlled phase 1/2a study (NCT03606512; https://www.clinicaltrials.gov/ct2/show/NCT03606512), RSV-seronegative toddlers aged 12-24 months received Ad26.RSV.preF (2.5×1010 vp) or placebo on Days 1, 29, and 57 (a meningococcal vaccine [Nimenrix] could substitute for Day 57 placebo). Primary endpoints were solicited local and systemic adverse events (AEs; 7 days post each vaccination), unsolicited AEs (28 days postvaccination), and serious AEs (SAEs; first vaccination until study end). Participants were monitored for RSV-respiratory tract infection (RTI) to assess infection rates and for severe RSV-lower respiratory tract infection (RSV-LRTI) as an indication of enhanced disease. RSV-A2 neutralizing, RSV (A and B) preF binding, and RSV postF immunoglobulin G binding antibodies were evaluated on Days 1 (pre-dose), 8, and 85, and post–RSV season 1. Thirty-eight participants were enrolled and vaccinated (Ad26.RSV.preF, n=20; placebo, placebo/Nimenrix, n=18). Solicited AEs were more common following Ad26.RSV.preF than placebo; most were mild/moderate. No vaccine-related SAEs were reported. Five of 19 participants receiving Ad26.RSV.preF and 2/18 receiving placebo or placebo/Nimenrix had confirmed RSV-RTI or RSV-associated otitis media; none were considered severe. At the final season 1 study visit, most Ad26.RSV.preF recipients had ≥2-fold increases from baseline in RSV-A2 neutralizing, RSV A and B preF binding, and RSV postF antibodies. Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers.