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

Background: the rvsvδg-zebov-gp vaccine prevented ebola virus disease when used at 2 × 107plaque-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 × 107pfu in 115 adults and a dose of 2 × 107pfu 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 × 107pfu 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 × 105pfu. adults with antibodies before vaccination had higher gmts throughout. neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105pfu. 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 × 107pfu dose in adults and support consideration of lower doses for paediatric populations and those who request boosting. © 2017,public library of science. all rights reserved.