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

Agnandji, ST; Fernandes, JF; Bache, EB; Obiang Mba, RM; Brosnahan, JS; Kabwende, L; Pitzinger, P; Staarink, P; Massinga-Loembe, M; Krähling, V; et al. Agnandji, ST; Fernandes, JF; Bache, EB; Obiang Mba, RM; Brosnahan, JS; Kabwende, L; Pitzinger, P; Staarink, P; Massinga-Loembe, M; Krähling, V; Biedenkopf, N; Fehling, SK; Strecker, T; Clark, DJ; Staines, HM; Hooper, JW; Silvera, P; Moorthy, V; Kieny, M-P; Adegnika, AA; Grobusch, MP; Becker, S; Ramharter, M; Mordmüller, B; Lell, B; VEBCON Consortium, ; Krishna, S; Kremsner, PG (2017) Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial. PLoS Med, 14 (10). e1002402. ISSN 1549-1676 https://doi.org/10.1371/journal.pmed.1002402
SGUL Authors: Staines, Henry Michael

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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.

Item Type: Article
Additional Information: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Keywords: General & Internal Medicine, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLoS Med
ISSN: 1549-1676
Language: eng
Dates:
DateEvent
6 October 2017Published
7 September 2017Accepted
Publisher License: Creative Commons: Public Domain Dedication
Projects:
Project IDFunderFunder ID
SPHQ14-LOA-255Wellcome Trusthttp://dx.doi.org/10.13039/100004440
SPHQ15-LOA-007Wellcome Trusthttp://dx.doi.org/10.13039/100004440
SPHQ14-LOA-327-REV1Bill and Melinda Gates Foundationhttp://dx.doi.org/10.13039/100000865
SPHQ14-LOA-327Bill and Melinda Gates Foundationhttp://dx.doi.org/10.13039/100000865
ZMV I 5-25 14 NIKBundesministerium für GesundheitUNSPECIFIED
UNSPECIFIEDLand Baden-WürttembergUNSPECIFIED
402-3-04-25German Center for Infection ResearchUNSPECIFIED
PubMed ID: 28985239
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/109199
Publisher's version: https://doi.org/10.1371/journal.pmed.1002402

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