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

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Publication

Citation

Tapia, Milagritos D., Samba O. Sow, Khardiata D. Mbaye, Aliou Thiongane, Birahim P. Ndiaye, Cheikh T. Ndour, Souleymane Mboup, Babajide Keshinro, Thompson N. Kinge, Guy Vernet, Jean Joel Bigna, Stephen Oguche, Kwadwo A. Koram, Kwaku P. Asante, Patrice Gobert, Wayne R. Hogrefe, Iris De Ryck, Muriel Debois, Patricia Bourguignon, Erik Jongert, William R. Ballou, Marguerite Koutsoukos, François Roman, Senate Amusu, Leo Ayuk, Catherine Bilong, Owusu Boahen, Makhtar Camara, Fadima Cheick Haidara, Daouda Coly, Siry Dièye, David Dosoo, Melanie Ekedi, Irma Eneida Almeida Dos Santos, Seyram Kaali, Afoke Kokogho, Myron Levine, Nick Opoku, Seth Owusu-Agyei, Simon Pitmang, Fatima Sall, Moussa Seydi, Marcelo Sztein, Mathurin Tejiokem, Awa Traore, Marie-Astrid Vernet, and Abena Kunadu Yawson. 2020. "Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial." The Lancet Infectious Diseases.

Abstract

Background

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.

Methods

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.

Findings

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 symptoms of thrombocytopenia were reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentrations (GMC) in the ChAd3-EBO-Z/MenACWY-TT group were 1564 (95% CI 1340–1826) for those aged 13–17 years, 1395 (1175–1655) for 6–12 years, and 2406 (1942–2979) for 1–5 years. Anti-glycoprotein Ebola virus IgG antibody responses persisted up to 12 months post-vaccination, with a GMC of 716 (95% CI 619–828) for those aged 13–17 years, 752 (645–876) for 6–12 years, and 1424 (1119–1814) for 1–5 years.

Interpretation

ChAd3-EBO-Z was immunogenic and well tolerated in children aged 1–17 years. This study provides the first ChAd3-EBO-Z data in a paediatric population. Further development should focus on multivalent approaches including Sudan and Marburg strains, and heterologous prime-boost strategies, for instance using modified vaccinia Ankara-based vaccine to boost the immune response.

Funding

EU's Horizon 2020 research and innovation programme and GlaxoSmithKline Biologicals SA.

Accessibility

Through subscription on Lancet

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