15 research outputs found
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 × 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
Reactogenicity to rVSVΔG-ZEBOV-GP vaccine until day 28 post-vaccination.
<p>Reactogenicity to rVSVΔG-ZEBOV-GP vaccine until day 28 post-vaccination.</p
Antibody responses to whole-virion ELISA (AEU/ml) by age group: Comparison of geometric mean concentration of IgG antibodies for children, adolescents, and adults vaccinated with the 2 × 10<sup>7</sup> PFU dose at day 0, 28, and 56.
<p>P < 0.05 indicates a statistical difference in antibody concentrations between age groups at the measured time points. AEU, arbitrary enzyme-linked immunosorbent assay units; ELISA, enzyme-linked immunosorbent assay; PFU, plaque-forming units; ZEBOV, Zaire Ebola virus.</p
Geometric mean titres, seropositivity rates, and proportions of seroresponders to rVSVΔG-ZEBOV-GP measured by ZEBOV PsVNA50 in adults.
<p>Geometric mean titres, seropositivity rates, and proportions of seroresponders to rVSVΔG-ZEBOV-GP measured by ZEBOV PsVNA50 in adults.</p
Glycoprotein antibody distribution by age group: Comparison of distribution of ZEBOV-GP IgG antibodies (AEU/ml) measured by USAMRIID ZEBOV-GP ELISA for dose 2 × 10<sup>7</sup> PFU administered to children, adolescents, and adults from day 0, 28, 56, 84, and 180.
<p>Data were not available for children and adolescents at D84. P < 0.05 indicates a statistical difference in ZEBOV-GP IgG between children, adolescents, and adults. AEU, arbitrary enzyme-linked immunosorbent assay units; ELISA, enzyme-linked immunosorbent assay; GP, glycoprotein; PFU, plaque-forming units; USAMRIID, US Army Medical Research Institute of Infectious Diseases; ZEBOV, Zaire Ebola virus.</p
Endpoint geometric mean titres measured by USAMRIID ZEBOV-GP ELISA in adults with and without baseline specific antibodies.
<p>Endpoint geometric mean titres measured by USAMRIID ZEBOV-GP ELISA in adults with and without baseline specific antibodies.</p
Geometric mean titres of ZEBOV antibodies in adults by baseline antibody status measured by whole-virion ELISA.
<p>Geometric mean titres of ZEBOV antibodies in adults by baseline antibody status measured by whole-virion ELISA.</p