Five-year immunogenicity and safety follow-up of the PREVAC randomized Trial of Vaccines for Zaire Ebola Virus Disease

Background: The World Health Organization has expanded its recommendations for prophylactic Ebola vaccination for at-risk populations. Durable vaccine-induced immunity is important for sustaining outbreak preparedness in regions with recurrent Ebola virus disease (EVD). We assessed five–year persistence of vaccine-induced immune responses in adults and children from the PREVAC trial. Methods: Two large randomised phase 2 trials ( NCT02876328 ), in adults and children aged ≥1 year, were conducted in four west African countries. Participants were randomly assigned to placebo or to one of three Ebola vaccine strategies: Ad26.ZEBOV followed by MVA–BN–Filo at 56 days; rVSVΔG–ZEBOV–GP followed by placebo; or rVSVΔG–ZEBOV–GP followed by a homologous booster dose at 56 days. After 12 months of follow-up, the primary results were published, participants unblinded to their vaccine assignment, and follow–up continued for 60 months. After Month 24, placebo group recipients were offered active vaccination. Anti Ebola virus glycoprotein Immunoglobulin G (IgG) concentrations were measured for 5 years. Findings: 1401 adults and 1401 children were initially randomized, and 1315 (93.9%) adults and 1322 (94.4%) children attended at least one long-term visit. Retention was high, with 95% followed beyond 1 year and 83% completion at 5-year follow-up. For the three vaccine strategies, antibody geometric mean concentrations (GMC) declined modestly between Months 12 and 24, followed by a stable plateau from Months 24 to 60. At Month 60, antibody GMC were higher in the rVSV-based groups (1099 and 1216 EU/ml for adults; 1982 and 2347 EU/ml for children) than in the Ad26.ZEBOV, MVA–BN–Filo group (252 adults and 645 EU/ml children). Antibody persistence at Month 60 was heterogeneous, varying by age, sex, country, and baseline IgG concentration. Interpretation: Licensed Ebola vaccines induced sustained antibody responses in adults and children for up to 5 years. While the protective antibody level is unknown, these data demonstrate long–lasting immune responses from currently employed vaccine strategies.