Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial

• Published in: The Lancet infectious diseases 2020-06, Vol.20 (6), p.719-730
• Main Authors: Tapia, Milagritos D, Sow, Samba O, Mbaye, Khardiata D, Thiongane, Aliou, Ndiaye, Birahim P, Ndour, Cheikh T, Mboup, Souleymane, Keshinro, Babajide, Kinge, Thompson N, Vernet, Guy, Bigna, Jean Joel, Oguche, Stephen, Koram, Kwadwo A, Asante, Kwaku P, Gobert, Patrice, Hogrefe, Wayne R, De Ryck, Iris, Debois, Muriel, Bourguignon, Patricia, Jongert, Erik, Ballou, William R, Koutsoukos, Marguerite, Roman, François, Amusu, Senate, Ayuk, Leo, Bilong, Catherine, Boahen, Owusu, Camara, Makhtar, Cheick Haidara, Fadima, Coly, Daouda, Dièye, Siry, Dosoo, David, Ekedi, Melanie, Eneida Almeida Dos Santos, Irma, Kaali, Seyram, Kokogho, Afoke, Levine, Myron, Opoku, Nick, Owusu-Agyei, Seth, Pitmang, Simon, Sall, Fatima, Seydi, Moussa, Sztein, Marcelo, Tejiokem, Mathurin, Traore, Awa, Vernet, Marie-Astrid, Yawson, Abena Kunadu
• Format: Article
• Language: English
• Subjects: Abnormalities; Adenoviruses; Antibodies; Children; Ebola virus; Ebolavirus; Enzyme-linked immunosorbent assay; Epidemics; Evaluation; Fatalities; Fever; Glycoproteins; IgG antibody; Immune response; Immune system; Immunization; Immunogenicity; Immunoglobulin G; Infectious diseases; Laboratories; Pan troglodytes; Randomization; Safety; Teenagers; Tetanus; Thrombocytopenia; Vaccination; Vaccines; Vaccinia; Viral diseases
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(20)30019-0

During the large 2013–16 Ebola virus outbreak caused by the Zaire Ebola virus, about 20% of cases were reported in children. This study is the first, to our knowledge, to evaluate an Ebola vaccine in children younger than 6 years. We aimed to evaluate the safety, reactogenicity, and immunogenicity of a monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in a paediatric population. This phase 2, randomised, observer-blind, controlled trial was done in a vaccine centre in Mali and a university hospital centre in Senegal. Healthy children were randomly assigned through a web-based system (1:1; stratified by age group, gender, and centre) to receive ChAd3-EBO-Z (day 0) and meningococcal serogroups A,C,W-135,Y tetanus toxoid conjugate vaccine (MenACWY-TT; month 6), or MenACWY-TT (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind from study start until interim day 30 analysis and became single-blind as of interim analysis. Primary outcomes assessed were serious adverse events (up to study end, month 12), solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0–6). As secondary endpoints, we evaluated anti-glycoprotein Zaire Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02548078. From Nov 11, 2015, to May 9, 2016, of 776 children screened for eligibility, 600 were randomly assigned (200 [33%] in each age strata: 1–5, 6–12, 13–17 years), 300 (50%) to the ChAd3-EBO-Z/MenACWY-TT group and 300 (50%) to the MenACWY-TT/ChAd3-EBO-Z group; all were included in the total vaccinated cohort. Post-day 0 vaccination, the most common solicited injection site symptom was pain (127 [42%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 60 [20%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group); the most common solicited general adverse event was fever (95 [32%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 28 [9%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group). Unsolicited adverse events post-day 0 vaccination were reported by 41 (14%) of 300 participants in the ChAd3-EBO-Z/MenACWY-TT group and 24 (8%) of 300 MenACWY-TT/ChAd3-EBO-Z recipients. Serious adverse events were reported for two (1%) of 300 children in each group; none were considered vaccination related. No clinical