Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus (RSV) Vaccine in Healthy RSV-Seropositive Children 12–23 Months of Age
Javier Díez‐Domingo, Xavier Sáez‐Llorens, M. Weber, Cristina Epalza, Archana Chatterjee, Cheng‐Hsun Chiu, Chien‐Yu Lin, Andrea A. Berry, Federico Martinón‐Torres, Fernando Baquero‐Artigao, Joanne M. Langley, José Tomás Ramos Amador, Joseph B. Domachowske, Li‐Min Huang, Nan‐Chang Chiu, Susanna Esposito, Philippe Moris, Thi Lien-Anh Nguyên, Vanja Nikic, Wayne Woo, Yingjun Zhou, Ilse Dieussaert, Amanda Leach, Antonio López, Nicolas Vanhoutte
Abstract
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 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12-23-month-old RSV-seropositive children followed up for 2 years after vaccination. METHODS: Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti-RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2. RESULTS: Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for 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 after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1. CONCLUSIONS: Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted. CLINICAL TRIALS REGISTRATION: NCT02927873.