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. 2024 Aug 8;11(9):ofae453.
doi: 10.1093/ofid/ofae453. eCollection 2024 Sep.

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

Joanne M Langley  1 , Terry M Nolan  2   3 , Mika Rämet  4 , Peter C Richmond  5   6 , Nelson Rosário Filho  7 , Wouter Haazen  8 , Sara P H van den Berg  8 , Kristi Williams  8 , Arangassery Rosemary Bastian  8 , Edmund Omoruyi  9 , Joanna Williams Durkin  10 , Nadine Salisch  8 , Gunter Van Geet  11 , Wilbert van Duijnhoven  11 , Esther Heijnen  8 , Benoit Callendret  8
Affiliations

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

Joanne M Langley et al. Open Forum Infect Dis. .

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.

Keywords: adenovirus serotype 26; pediatric vaccination; respiratory syncytial virus; respiratory syncytial virus vaccine.

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Conflict of interest statement

Potential conflicts of interests. J. M. L.'s employer, Dalhousie University, received funding from Janssen to complete this study; J. M. L.'s employer has received research grants from Pfizer, GSK, Merck, and Moderna to conduct clinical trials to prevent RSV. T. M. N. has been a data safety monitoring board member for vaccine studies conducted by Moderna, Clover, Novavax, CSL Seqirus, Arcturus, and SK Bioscience Korea; T. M. N. has received payment for advisory roles on vaccines from AstraZeneca, Moderna, MSD, Sanofi, CSL, and Pfizer; and T. M. N.'s employers, University of Melbourne and MCRI, have received funding to contribute to clinical trials sponsored by Moderna, Iliad, Dynavax, MSD, Sanofi, CSL Seqirus, and Pfizer. M. R. was employed by Tampere University (currently Finnish Vaccine Research Ltd.), which carries out clinical vaccine trials for Janssen and several other vaccine manufacturers. P. C. R.'s employer, University of Western Australia, has received research funding for RSV clinical trials, for this study from Janssen and from Novavax, Merck, AstraZeneca, Pfizer, and GSK; for investigator-led research from Merck and Sanofi; and for P. C. R.'s involvement in advisory boards from Merck, Pfizer, GSK, Sanofi, and Novavax. P. C. R. is also a member of the ReSViNET Board, which is an international advocacy group for RSV awareness, treatment, and prevention. N. R. F. received speaker fees from Sanofi, Novartis, AstraZeneca, GSK, AbbVie, Chiesi, Viatris, Danone, and Pfizer; and received research grants from AstraZeneca, Viatris, Sanofi-Regeneron, Janssen, Eurofarma, and Vertex. W. H., S. P. H. v. d. B., K. W., and N. S. are employees of Janssen Vaccines & Prevention B.V. and may own stock or stock options. E. O. formerly worked at Janssen Infectious Diseases as a consultant. J. W. D. is an employee of Janssen Biologics Europe. G. V. G. and W. v. D. are employees of Janssen Research & Development. A. R. B., E. H., and B. C. are former employees of Janssen Vaccines & Prevention B.V.

Figures

Figure 1.
Figure 1.
Participant disposition. RSV, respiratory syncytial virus; vp, viral particle. aSeventy-two prospective participants had failed screenings, 59 because of RSV seropositivity. bOne participant discontinued the study vaccine after the second dose because of an unsolicited adverse event (urticaria) that was considered related to the study vaccine. cOne participant was lost to follow-up. The participant who discontinued the study vaccine because of an adverse event (urticaria) subsequently discontinued the study for other reasons (moved from study area).
Figure 2.
Figure 2.
All solicited local AEs by worst severity grade after any vaccination (full analysis set). Ad26, adenovirus type 26 vector; AE, adverse event.
Figure 3.
Figure 3.
All solicited systemic AEs by worst severity grade after any vaccination (full analysis set). Ad26, adenovirus type 26 vector; AE, adverse event.
Figure 4.
Figure 4.
Titers of (A) RSV-A2 strain neutralizing antibodies and (B) RSV A preF, (C) RSV B preF, and (D) RSV postF binding antibodies (per-protocol immunogenicity analysis set). Ad26, adenovirus type 26 vector; ELISA, enzyme-linked immunosorbent assay; EoS, end of the first RSV season after study vaccination; EU, ELISA units; GMFI, geometric mean fold increase; GMT, geometric mean titer; postF, RSV postfusion conformation F protein; preF, RSV prefusion conformation F protein; RSV, respiratory syncytial virus; vp, viral particle.
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