Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults 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., Ndiaye BP; Le Dantec Laboratory of Bacteriology and Virology, Dakar, Senegal; Institut de Recherche en Santé, de Surveillance Epidemiologique et de Formations, Dakar, Senegal., Mbaye KD; University Cheikh Anta Diop, Dakar, Sénégal., Thiongane A; University Cheikh Anta Diop, Dakar, Sénégal., Ndour CT; University Cheikh Anta Diop, Dakar, Sénégal., Mboup S; Le Dantec Laboratory of Bacteriology and Virology, Dakar, Senegal; Institut de Recherche en Santé, de Surveillance Epidemiologique et de Formations, Dakar, Senegal., Ake JA; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA., Keshinro B; Walter Reed Program, Abuja, Nigeria., Akintunde GA; 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 & 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., Hogrefe WR; Q(2) Solutions, San Juan Capistrano, CA, USA., Günther S; Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany., Naficy A; Quintiles, La Défense Cedex, France., 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. 707-718. Date of Electronic Publication: 2020 Mar 19.
DOI:	10.1016/S1473-3099(20)30016-5
Abstrakt:	Background: The 2014 Zaire Ebola virus disease epidemic accelerated vaccine development for the virus. We aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in adults. Methods: This phase 2, randomised, observer-blind, controlled trial was done in study centres in Cameroon, Mali, Nigeria, and Senegal. Healthy adults (≥18 years) were randomly assigned with a web-based system (1:1; minimisation procedure accounting for age, gender, centre) to receive ChAd3-EBO-Z (day 0), or saline placebo (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind until planned interim day 30 analysis, single-blind until month 6, and open-label after month 6 vaccination. Primary outcomes assessed in the total vaccinated cohort, which comprised all participants with at least one study dose administration documented, were serious adverse events (up to study end, month 12); and for a subcohort were 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). Secondary endpoints (subcohort; per-protocol cohort) evaluated anti-glycoprotein Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02485301. Findings: Between July 22, 2015, and Dec 10, 2015, 3030 adults were randomly assigned; 3013 were included in the total vaccinated cohort (1509 [50·1%] in the ChAd3-EBO-Z group and 1504 [49·9%] in the placebo/ChAd3-EBO-Z group), 17 were excluded because no vaccine was administered. The most common solicited injection site symptom was pain (356 [48%] of 748 in the ChAd3-EBO-Z group vs 57 [8%] of 751 in the placebo/ChAd3-EBO-Z group); the most common solicited general adverse event was headache (345 [46%] in the ChAd3-EBO-Z group vs 136 [18%] in the placebo/ChAd3-EBO-Z group). Unsolicited adverse events were reported by 123 (16%) of 749 in the ChAd3-EBO-Z group and 119 (16%) of 751 in the placebo/ChAd3-EBO-Z group. Serious adverse events were reported for 11 (1%) of 1509 adults in the ChAd3-EBO-Z group, and 18 (1%) of 1504 in the placebo/ChAd3-EBO-Z group; none were considered vaccination-related. No clinically meaningful thrombocytopenia was reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentration was 900 (95% CI 824-983) in the ChAd3-EBO-Z group. There were no treatment-related deaths. Interpretation: ChAd3-EBO-Z was immunogenic and well tolerated in adults. Our findings provide a strong basis for future development steps, which should concentrate on multivalent approaches (including Sudan and Marburg strains). Additionally, prime-boost approaches should be a focus with a ChAd3-based vaccine for priming and boosted by a modified vaccinia Ankara-based vaccine. 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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