Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study

• Published in: The Lancet infectious diseases 2016-03, Vol.16 (3), p.311-320
• Main Authors: De Santis, Olga, MRes, Audran, Régine, PhD, Pothin, Emilie, PhD, Warpelin-Decrausaz, Loane, PhD, Vallotton, Laure, MD, Wuerzner, Grégoire, MD, Cochet, Camille, MD, Estoppey, Daniel, MD, Steiner-Monard, Viviane, MD, Lonchampt, Sophie, MSc, Thierry, Anne-Christine, BS, Mayor, Carole, BS, Bailer, Robert T, PhD, Mbaya, Olivier Tshiani, MD, Zhou, Yan, PhD, Ploquin, Aurélie, PhD, Sullivan, Nancy J, PhD, Graham, Barney S, MD, Roman, François, MD, De Ryck, Iris, MD, Ballou, W Ripley, MD, Kieny, Marie Paule, PhD, Moorthy, Vasee, MD, Spertini, François, MD, Genton, Blaise, Prof
• Format: Article
• Language: English
• Subjects: Adenoviridae; Adenoviridae - classification; Adenovirus; Adenoviruses; Adult; Antibodies, Viral - blood; Clinical trials; Dose-Response Relationship, Immunologic; Ebola Vaccines - administration & dosage; Ebola Vaccines - adverse effects; Ebola Vaccines - immunology; Ebola virus; Ebolavirus - immunology; Epidemics; Female; Fever - chemically induced; Health care; Hemorrhagic Fever, Ebola - prevention & control; Hemorrhagic Fever, Ebola - virology; Humans; Immunogenicity; Immunoglobulin G - blood; Infectious Disease; Infectious diseases; Male; Middle Aged; Military Personnel; Pan troglodytes; Public health; Safety; Vaccines; Vaccines, DNA - immunology; Young Adult
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(15)00486-7

Summary Background The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). Methods We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18–65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 1010 viral particles), low-dose vaccine (2·5 × 1010 viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT02289027. Findings Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola gly