Safety and immunogenicity of a ChAd155-vectored RSV vaccine (ChAd155-RSV) in healthy RSV-seropositive children 12-23 months of age

Background: Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing the F-, N- and M2-1 proteins, administered to 12-23-month-old RSV-seropositive children followed for 2 years post-vaccination. Methods: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (1:1) (Day 1 and 31). Doses escalated from 0.5 × 1010 low (LD) to 1.5 × 1010 medium (MD) to 5 × 1010 high (HD) viral particles after safety assessment. Study endpoints included anti-RSV-A neutralizing antibody (Nab) titers through Year 1, and safety through Year 2. Results: Eighty-two participants were vaccinated: 11 RSV-LD, 14 RSV-MD, 18 RSV-HD, 39 placebo. Solicited adverse events were similar across groups, except fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups post-dose 1 without further increase post-dose 2. RSV-A Nab titers remained higher than pre-vaccination levels at Year 1. Conclusions: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed post-dose 1 with no observed booster effect post-dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. Trial registration: clinicaltrials.gov NCT02927873, URL: https://www.clinicaltrials.gov/ct2/show/NCT02927873.