Efficacy and safety of Ebola vaccines in children: a systematic review and meta-analysis

Abstract Background Ebola virus disease is a fever with high case-fatality rates and disproportionate impacts on children. Ebola vaccines have shown efficacy in adults, evidence on their performance in children remains limited. This meta-analysis assesses the efficacy and safety of Ebola vaccines in pediatric populations, to inform immunization strategies and outbreak preparedness. Methods Following PRISMA statement, we included trials in Phase IIb-IV trials and post-marketing studies retrieved from PubMed, SCOPUS, Web of Science, ClinicalTrial.gov, ISRCTN, EUCTR, CTIS, PACTR, evaluating any Ebola vaccine (Ad26.ZEBOV and MVA-BN-Filo, rVSV-ΔG-ZEBOV, ChAd3 EBO-Z) in children (<18 years), with comparators receiving no vaccine or alternative vaccines. The outcomes were immunogenicity (seroconversion) and safety (serious adverse events, SAEs). Proportion and head-to-head meta-analyses were performed with subgroup analyses by vaccine type. Results Seven datasets (110,258 participants) were included. After the first dose, pooled seroconversion was 89%: rVSV 92%, Ad26/MVA 82%, ChAd 99%. After full vaccination, it rose to 96%: rVSV 92% and 96% (one vs two doses), Ad26/MVA 98%, ChAd 99%. At one year, seroconversion declined slightly to 91%. Head-to-head meta-analyses showed RR = 15.06 (p < 0.001) after the first dose, RR = 16.88 (p < 0.001) after full vaccination, and RR = 7.7 (p = 0.005) at one year. No major differences were observed between one and two rVSV doses (RR 8.24 vs 8.47, p = 0.05). rVSV and Ad26/MVA maintained high immunogenicity across timepoints. SAEs were 1% (RR = 0.86, p = 0.834), mostly unrelated to vaccination. Conclusions Ebola vaccines are immunogenic and well-tolerated in children, with one dose of rVSV showing slightly superior short-term performance and Ad26/MVA achieving robust responses at completion. These results support including children in Ebola vaccination campaigns. Immunization protocols should be tailored considering vaccine-specific profiles and outbreak contexts. Key messages • Ebola vaccines are safe and highly immunogenic in children, supporting their inclusion in both outbreak responses and scheduled vaccination. • rVSV-ΔG-ZEBOV and Ad26.ZEBOV/MVA-BN-Filo vaccines offer different immunogenicity profiles; both are viable pediatric options.