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Clinical Trial
. 2022 Dec 28;227(1):71-82.
doi: 10.1093/infdis/jiac407.

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months

Arabella S V Stuart  1 , Miia Virta  2 , Kristi Williams  3 , Ilkka Seppa  2 , Robyn Hartvickson  4 , Melanie Greenland  1 , Edmund Omoruyi  5 , Arangassery Rosemary Bastian  3 , Wouter Haazen  3 , Nadine Salisch  3 , Efi Gymnopoulou  5 , Benoit Callendret  3 , Saul N Faust  6   7 , Matthew D Snape  1   8 , Esther Heijnen  3
Affiliations
Clinical Trial

Phase 1/2a Safety and Immunogenicity of an Adenovirus 26 Vector Respiratory Syncytial Virus (RSV) Vaccine Encoding Prefusion F in Adults 18-50 Years and RSV-Seropositive Children 12-24 Months

Arabella S V Stuart et al. J Infect Dis. .

Abstract

Background: Respiratory syncytial virus (RSV) remains a leading cause of pediatric morbidity, with no approved vaccine. We assessed the safety and immunogenicity of the Ad26.RSV.preF vaccine candidate in adults and children.

Methods: In this randomized, double-blind, phase 1/2a, placebo-controlled study, 12 adults (18-50 years) and 36 RSV-seropositive children (12-24 months) were randomized 2:1 to Ad26.RSV.preF (1 × 1011 viral particles [vp] for adults, 5 × 1010 vp for children) or placebo, at day 1 and 29, with 6-month immunogenicity and 1-year safety follow-up. Respiratory syncytial virus infection was an exploratory outcome in children.

Results: In adults, solicited adverse events (AEs) were generally mild to moderate, with no serious AEs. In children, no vaccination-related serious AEs were reported; fever was reported in 14 (58.3%) Ad26.RSV.preF recipients. Baseline pediatric geometric mean titers for RSV A2 neutralization increased from 121 (95% confidence interval [CI], 76-191) to 1608 (95% CI, 730-3544) at day 29, and 2235 (95% CI, 1586-3150) at day 57, remaining elevated over 7 months. Respiratory syncytial virus infection was confirmed in fewer children receiving Ad26.RSV.preF (1, 4.2%) than placebo (5, 41.7%).

Conclusions: Ad26.RSV.preF demonstrated immunogenicity in healthy adults and toddlers, with no safety concerns raised. Evaluations in RSV-seronegative children are underway.

Keywords: adenovirus vectors; pediatric; respiratory syncytial virus; seropositive; vaccine.

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Conflict of interest statement

Potential conflicts of interest. M. D. S. was an NIHR Senior Investigator and receives salary support from the Oxford NIHR Biomedical Research Centre when undertaking this work. S. N. F. is an NIHR Senior Investigator and receives salary support from the NIHR Southampton Clinical Research Facility and Biomedical Research Centre. K. W., A. R. B., W. H., N. S., E. G., E. O., and B. C., and E. H. are employees of Janssen and may be Johnson & Johnson stockholders. M. D. S. received research grants (through The University of Oxford) from the following: GlaxoSmithKline, Pfizer, Janssen, MCM vaccines, MedImmune, and AstraZeneca, vaccine from Novavax for COVID-19 vaccine studies. He received no personal payment for this work. MDS was a member of medical advisory boards for the Meningitis Research Foundation. From September 2022 MDS is employed by Moderna Biotech UK; this work was completed prior to this employment. S. N. F. received research grants (through University Hospital Southampton) from the following: Johnson & Johnson, Pfizer, Sanofi, GlaxoSmithKline, Merck, AstraZeneca, and Valneva; honoraria from Johnson & Johnson and Pfizer; he has been an advisor for AstraZeneca, MedImmune, Sanofi, Pfizer, Seqirus, Merck, Johnson & Johnson, and GlaxoSmithKline (but received no personal payments for this work, all honoraria were paid to University Hospital Southampton NHS Foundation Trust); and he acted as a paid chair of UK NICE Sepsis and Lyme Disease Guidelines. I. S. received expenses from Janssen to cover travel to an investigator meeting. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Consort flow of participants by cohort. Ad26.RSV.preF, adenovirus serotype 26 prefusion conformation-stabilized F protein; IMP, investigational medicinal product; RSV, respiratory syncytial virus; vp, viral particles.
Figure 2.
Figure 2.
Solicited local adverse events in days 0–7 postvaccination by worst severity grade, dose, and study arm in children (full analysis set, Ad26.RSV.preF n = 24, placebo n = 12). Ad26.RSV.preF, adenovirus serotype 26 prefusion conformation-stabilized F protein.
Figure 3.
Figure 3.
Solicited systemic adverse events in days 0–7 postvaccination by worst severity grade, dose, and study arm in children (full analysis set, Ad26.RSV.preF n = 24, placebo n = 12). Ad26.RSV.preF, adenovirus serotype 26 prefusion conformation-stabilized F protein.
Figure 4.
Figure 4.
Neutralizing antibody titers over time in children (per-protocol immunogenicity set*, n = 26). (A) Respiratory syncytial virus (RSV) A2 strain. (B) Pre-fusion (pre-F) antibodies. (C) Post-fusion (post-F) antibodies, (D) neutralizing antibodies over time, by participant. Geometric mean with 95% confidence interval shown in the figure. N, number of participants with data at baseline. *Data for some subjects are not available due to no sample availability and/or low sample quality for the planned immunogenicity analyses. Ad26.RSV.preF, adenovirus serotype 26 prefusion conformation-stabilized F protein; ELISA, enzyme-linked immunosorbent assays; EU, ELISA units; GMT, geometric mean titer; vp, viral particles.
Figure 5.
Figure 5.
Total cytokine response (mock subtracted intracellular cytokine staining) over time in children (per-protocol immunogenicity set*, n = 22). (A) CD4+ T-cell response. (B) CD8+ T-cell response. Values below 0.001% were imputed with 0.0005%. Total cytokine response after in vitro respiratory syncytial virus (RSV) F-protein peptide stimulation was reported as the percentage of CD4+ and CD8+ T cells that produce at least 1 of 3 cytokines (interferon γ [IFNγ], tumor necrosis factor α, and/or interleukin-2). Th1-type response was defined as an increase in the percentage of CD4+IFNγ+ T cells. *Data for some subjects are not available due to no sample availability and/or low sample quality for the planned immunogenicity analyses. †n = 13 with sample available after day 1. Ad26.RSV.preF, adenovirus serotype 26 prefusion conformation-stabilized F-protein; F-protein, fusion protein; vp, viral particles.
Figure 6.
Figure 6.
T-helper cell type 1 (Th1) and Th2 profiles in children (per-protocol immunogenicity set*, n = 21). Values below 0.001% were imputed with 0.0005%. *Data for some subjects are not available due to no sample availability and/or low sample quality for the planned immunogenicity analyses. Ad26.RSV.preF, adenovirus serotype 26 prefusion conformation-stabilized F protein.
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