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

Overview

Journal Open Forum Infect Dis

Specialty Infectious Diseases

Date 2024 Sep 2

PMID 39220658

Authors

Joanne M Langley

Terry M Nolan

Mika Ramet

Peter C Richmond

Nelson Rosario 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 Callendret

Affiliations

Soon will be listed here.

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 × 10 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.

Citing Articles

Preventing RSV Infection in Children: Current Passive Immunizations and Vaccine Development.

Babawale P, Martinez-Espinoza I, Mitchell A, Guerrero-Plata A Pathogens. 2025; 14(2).

PMID: 40005481 PMC: 11858734. DOI: 10.3390/pathogens14020104.

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