Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6–7 Months of age: A Phase 1/2 Randomized Trial
Xavier Sáez‐Llorens, Ximena Norero, Marisa Márcia Mussi‐Pinhata, Kathia Luciani, Ignacio Salamanca de la Cueva, Javier Díez‐Domingo, Eduardo López‐Medina, Cristina Epalza, Jerzy Brzostek, Henryk Szymański, François D. Boucher, Benhur Şirvan Çetin, Tirza De León, Ener Çağrı Dinleyici, Miguel Ángel Marín Gabriel, Tolga İ̇nce, Mercedes Macías-Parra, Joanne M. Langley, Federico Martinón‐Torres, Mika Rämet, Ernest Kuchar, Jorge Pinto, Thanyawee Puthanakit, Fernando Baquero‐Artigao, Guido Castelli Gattinara, J.M. Merino Arribas, José Tomás Ramos Amador, Leszek Szenborn, Bruce Tapiéro, Evan J. Anderson, James D. Campbell, Saul N. Faust, Vanja Nikic, Yingjun Zhou, Wenji Pu, Damien Friel, Ilse Dieussaert, Antonio López, Roderick McPhee, Sonia Stoszek, Nicolas Vanhoutte
Abstract
BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.