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

A novel Ad26 vector-based RSV vaccine encoding preF-protein given as 2 doses in a double-blind RCT of 12 adults and 36 RSV-seropositive toddlers showed acceptable safety and tolerability up to 1 year, with evidence of humoral and cellular immunogenicity. 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 x 10(11) viral particles [vp] for adults, 5 x 10(10) 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.

Automated summary

A randomized, double-blind study in adults and children showed that a novel Ad26 vector-based RSV vaccine encoding preF-protein given as two doses demonstrated acceptable safety and tolerability up to 1 year, with evidence of humoral and cellular immunogenicity.