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

Autor:	Tapia MD; Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: mtapia@som.umaryland.edu., Sow SO; Centre pour le Développement des Vaccins, Bamako, Mali., Mbaye KD; University Cheikh Anta Diop, Dakar, Senegal., Thiongane A; University Cheikh Anta Diop, Dakar, Senegal., Ndiaye BP; Le Dantec Laboratory of Bacteriology and Virology, Dakar, Senegal; Institut de Recherche en Santé, de Surveillance Epidemiologique et de Formations, Dakar, Senegal., Ndour CT; University Cheikh Anta Diop, Dakar, Senegal., Mboup S; Le Dantec Laboratory of Bacteriology and Virology, Dakar, Senegal; Institut de Recherche en Santé, de Surveillance Epidemiologique et de Formations, Dakar, Senegal., Keshinro B; Walter Reed Program, Abuja, Nigeria., Kinge TN; Bamenda Regional Hospital, Bamenda, Cameroon., Vernet G; Centre Pasteur du Cameroun, Yaounde, Cameroon., Bigna JJ; Centre Pasteur du Cameroun, Yaounde, Cameroon., Oguche S; University of Jos and Jos University Teaching Hospital, Jos, Nigeria., Koram KA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana., Asante KP; Kintampo Health Research Centre, Kintampo, Ghana., Gobert P; Quintiles, La Defense Cedex, France., Hogrefe WR; Q(2) Solutions, San Juan Capistrano, CA, USA., De Ryck I; GSK, Wavre, Belgium., Debois M; GSK, Wavre, Belgium., Bourguignon P; GSK, Wavre, Belgium., Jongert E; GSK, Wavre, Belgium., Ballou WR; GSK, Rockville, MD, USA., Koutsoukos M; GSK, Wavre, Belgium., Roman F; GSK, Wavre, Belgium.
Jazyk:	angličtina
Zdroj:	The Lancet. Infectious diseases [Lancet Infect Dis] 2020 Jun; Vol. 20 (6), pp. 719-730. Date of Electronic Publication: 2020 Mar 19.
DOI:	10.1016/S1473-3099(20)30019-0
Abstrakt:	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. (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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