Safety and immunogenicity of the Ad26/protein preF RSV vaccine in adults aged 18 to 59 years with and without at-risk comorbidities for severe respiratory syncytial virus disease: A phase 3, randomized, controlled, immunobridging trial

Abstract

Background: Respiratory syncytial virus (RSV) causes a significant disease burden in adults with chronic comorbidities. Rates of severe RSV disease and death are as high, or higher in younger adults with risk factors than in healthy older adults in whom RSV vaccination is recommended. We conducted an immunobridging study using the Ad26/protein RSV preF vaccine, which previously demonstrated efficacy in adults aged ≥65 years to support extrapolation of efficacy demonstrated in an older population to younger adult populations at high risk of severe RSV disease.

Methods: This Phase 3 randomized, double-blind, placebo-controlled trial assessed the safety/tolerability and immunogenicity of Ad26/protein preF RSV in adults aged 18-59 years without (Cohort 1) and with (Cohort 2) chronic cardiac or pulmonary comorbidities, compared to adults aged ≥65 years (Cohort 3) in whom efficacy against RSV disease was demonstrated. Humoral and cellular immune responses were assessed at baseline, Days 15 and 183. Reactogenicity and safety were assessed in all participants.

Results: 1118 participants were enrolled (Cohort 1: 387; Cohort 2: 388; Cohort 3: 343). Compared to adults aged ≥65 years RSV neutralizing antibody titers were non-inferior in adults aged 18-59 years, including those at high risk. Levels of pre-F A IgG antibodies and frequencies of RSV-F specific interferon-gamma T-cells increased by Day 15 post-vaccination, and remained above baseline for at least 6 months in all cohorts. Reactogenicity and safety were clinically acceptable but age-dependent, with higher rates of Grade 3 systemic adverse events in adults aged 18-59-years than adults ≥65 years.

Conclusion: Ad26/protein preF RSV vaccine induced robust humoral and cellular immune responses in adults aged 18-59 years with or without chronic cardiac or pulmonary comorbidities, of similar magnitude to responses in older adults, allowing inference of efficacy and protection against RSV-associated respiratory disease in this population. www.

Clinicaltrials: govNCT05070546.

Keywords: Adult; Comorbidity; Immunogenicity; Respiratory syncytial virus; Safety; Vaccine.