Immunogenicity and safety of Ebola vaccines in children: A systematic review and meta-analysis

Ebola virus disease has high fatality rates and disproportionately affects children. This meta-analysis evaluated the immunogenicity and safety of Ebola vaccines in children to guide immunization strategies and outbreak preparedness.

Following PRISMA, Phase IIb-IV trials and postmarketing studies published up to March 2025 were retrieved from major databases. Eligible studies assessed Ad26.ZEBOV/MVA-BN-Filo, rVSV-ΔG-ZEBOV, or ChAd3 EBO-Z in children (<18 years) versus no or alternative vaccines. Outcomes included immunogenicity (seroconversion) and safety (serious adverse events, SAEs). Meta-analyses were performed, including subgroup and head-to-head comparisons. (PROSPERO registration: CRD420251020027).

Seven datasets (110 258 participants; 50.7% female) were included. After the first dose, pooled seroconversion was 89% (I² = 97.3%). After full vaccination, it rose to 96% (I² = 90.7%). At one year, it declined slightly to 91% (I² = 96.5%). Head-to-head meta-analyses showed RR = 13.95 (I² = 91.0%, P<0.001) after one dose, 16.88 (I² = 89.2%, P<0.001) after full vaccination, and 7.7 (I² = 65.2%, P = 0.005) at one year. SAEs were 1% (RR = 0.86, I² = 85%, P = 0.834), mostly unrelated to vaccination.

Ebola vaccines are safe and immunogenic in children. Findings support including children in vaccination campaigns, tailoring protocols to vaccine profiles and outbreak contexts.

Review has no specific or external funding but is supported by the review team institution ("Sapienza" University of Rome).

RESEARCH IN CONTEXT : EVIDENCE BEFORE THIS STUDY: We searched across multiple databases, including PubMed, SCOPUS, Web of Science, for previously published systematic reviews and meta-analyses on immunogenicity and safety of Ebola vaccines in the pediatric population. The final search was completed in March 2025 and included studies published up to that date. The search strategy used combinations of the following terms: ("Ebola vaccine" OR "rVSV-ΔG-ZEBOV" OR "Ad26.ZEBOV" OR "MVA-BN-Filo" OR "ChAd3 EBO-Z") AND ("children" OR "pediatric" OR "infant" OR "adolescent") AND ("immunogenicity" OR "antibody" OR "seroconversion" OR "safety" OR "adverse events"). We found no previous systematic reviews or meta-analyses specifically focused on pediatric Ebola vaccination. In particular, no previous synthesis had evaluated seroconversion rates after the first and full vaccination doses, long-term immunogenicity, or the comparative safety of these vaccines in children.

To our knowledge, this is the first meta-analysis to systematically synthesize immunogenicity and safety data for all available Ebola vaccine platforms in pediatric populations. The findings confirm that Ebola vaccines are safe and elicit strong immune responses in children, supporting their use both in outbreak settings and in planned immunization strategies. Although rVSV-ΔG-ZEBOV and Ad26.ZEBOV and MVA-BN-Filo vaccines exhibit distinct immunogenicity profiles, both represent viable options for pediatric vaccination.

Available evidence supports the inclusion of children in Ebola vaccination strategies. rVSV-ΔG-ZEBOV and Ad26.ZEBOV and MVA-BN-Filo vaccines are both viable pediatric options, each with specific immunogenicity profiles that should guide protocol selection depending on outbreak context and logistical feasibility. Immunization policies should also consider vaccine-specific schedules, long-term protection, and potential co-administration with other routine childhood vaccines. Further research is needed to assess vaccine performance in younger age groups, including infants and neonates, and to evaluate the long-term effectiveness and immunological memory beyond one year. Continued monitoring of safety and the impact of booster doses or heterologous regimens is essential to inform future guidelines.