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PLoS Med. 2017 Oct 6;14(10):e1002402. doi: 10.1371/journal.pmed.1002402. eCollection 2017 Oct.

Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

Author information

1
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
2
Institut für Tropenmedizin, Universitätsklinikum Tübingen, Tübingen, Germany.
3
German Centre for Infection Research (DZIF) partner sites Universitätsklinikum Tübingen and Gießen-Marburg-Langen, Germany.
4
Bernhard Nocht Hospital for Tropical Diseases, Bernhard Nocht Institute for Tropical Medicine and University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
6
Institute for Virology, Philipps-Universität Marburg, Marburg, Germany.
7
Centre for Diagnostics and Antimicrobial Resistance, Institute for Infection & Immunity, St. George's, University of London, London, United Kingdom.
8
US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.
9
World Health Organization, Geneva, Switzerland.
10
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
11
St. George's University Hospitals NHS Foundation Trust, London, United Kingdom.

Abstract

BACKGROUND:

The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data.

METHODS AND FINDINGS:

A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine induced high GMTs of ZEBOV-GP-specific antibodies at day 28 in adolescents, 1,428 (95% CI: 1,025-1,989), and children, 1,620 (95% CI: 806-3,259), and in both groups antibody titres increased up to day 180. The absence of a control group, lack of stratification for baseline antibody status, and imbalances in male/female ratio are the main limitations of this study.

CONCLUSIONS:

Our data confirm the acceptable safety and immunogenicity profile of the 2 × 107 PFU dose in adults and support consideration of lower doses for paediatric populations and those who request boosting.

TRIAL REGISTRATION:

Pan African Clinical Trials Registry PACTR201411000919191.

PMID:
28985239
PMCID:
PMC5630143
DOI:
10.1371/journal.pmed.1002402
[Indexed for MEDLINE]
Free PMC Article

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