Article
Author: Macias-Parra, Mercedes ; Langley, Joanne M ; De Leon, Tirza ; Anderson, Evan J ; Dinleyici, Ener Cagri ; Stoszek, Sonia K ; Ramos Amador, Jose Tomas ; Szymański, Henryk ; Faust, Saul N ; Díez-Domingo, Javier ; Lopez, Antonio Gonzalez ; McPhee, Roderick ; Pinto, Jorge ; Nikic, Vanja ; Campbell, James D ; Sáez-Llorens, Xavier ; Puthanakit, Thanyawee ; Gabriel, Miguel Ángel Marín ; Friel, Damien ; Cetin, Benhur S ; Pu, Wenji ; Martinón-Torres, Federico ; Lopez-Medina, Eduardo ; Arribas, Jose Manuel Merino ; Ince, Tolga ; Tapiero, Bruce ; Rämet, Mika ; de la Cueva, Ignacio Salamanca ; Zhou, Yingjun ; Luciani, Kathia ; Kuchar, Ernest ; Szenborn, Leszek ; Baquero-Artigao, Fernando ; Mussi-Pinhata, Marisa Márcia ; Brzostek, Jerzy ; Vanhoutte, Nicolas ; Gattinara, Guido Castelli ; Dieussaert, Ilse ; Norero, Ximena ; Epalza, Cristina ; Boucher, François D
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.