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

• Published in: Open forum infectious diseases Vol. 11; no. 9; p. ofae453
• Main Authors: Langley, Joanne M, Nolan, Terry M, Rämet, Mika, Richmond, Peter C, Rosário Filho, Nelson, Haazen, Wouter, van den Berg, Sara P H, Williams, Kristi, Bastian, Arangassery Rosemary, Omoruyi, Edmund, Williams Durkin, Joanna, Salisch, Nadine, Van Geet, Gunter, van Duijnhoven, Wilbert, Heijnen, Esther, Callendret, Benoit
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.09.2024
• Subjects: pediatric vaccination; adenovirus serotype 26; respiratory syncytial virus vaccine; respiratory syncytial virus
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofae453

Abstract 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 viral particles) 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 after each vaccination), unsolicited AEs (28 days postvaccination), and serious AEs (first vaccination until study end). Participants were monitored for RSV-respiratory tract infection to assess infection rates and for severe RSV-lower respiratory tract infection 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 (predose), 8, and 85, and after 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 serious AEs were reported. Five of 19 participants receiving Ad26.RSV.preF and 2/18 receiving placebo or placebo/Nimenrix had confirmed RSV-respiratory tract infection 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. In this phase 1/2a study, 3 doses of the Ad26.RSV.preF vaccine (2.5 × 1010 vp) was well tolerated and elicited an immunogenic response in RSV-seronegative toddlers aged 12–14 months through 2 RSV seasons.