A Phase 1/2a Study Evaluating Safety and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers Aged 12-24 Months
Joanne M Langley, Terry M Nolan, Mika Rämet, Peter C Richmond, Nelson Rosário Filho, Wouter Haazen, Sara P H van den Berg, Kristi Williams, Arangassery Rosemary Bastian, Edmund Omoruyi, Joanna Williams Durkin, Nadine Salisch, Gunter Van Geet, Wilbert van Duijnhoven, Esther Heijnen, Benoit CallendretAbstract
Background
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.
Methods
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.
Results
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.
Conclusions
Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers.