Long-term safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen: a cohort study of previously vaccinated adults and children in Sierra Leone (the EBOVAC-Salone extension study)

Background Ebola virus (EBOV) has caused large outbreaks in sub-Saharan Africa with devastating consequences. The two-dose Ad26.ZEBOV, MVA-BN-Filo vaccine regimen was safe and immunogenic in several studies. However, data on the regimen's long-term safety and immunogenicity are limited. Methods The EBOVAC-Salone Extension cohort study (NCT03820739) was conducted in Sierra Leone from July 2019 to July 2022. Adults and children who received at least one dose of the Ad26.ZEBOV, MVA-BN-Filo regimen in a previous trial (EBOVAC-Salone) were followed for five and four years respectively post-dose 1 (cohort 1). The study also followed one child for five years who was conceived by a female participant within three months of Ad26.ZEBOV vaccination (cohort 2). Primary outcomes were long-term safety, assessed for all participants by recording all serious adverse events (SAEs) and, in a subset of cohort 1, concentrations of binding antibodies against EBOV glycoprotein using the Filovirus Animal Non-Clinical Group enzyme-linked immunosorbent assay. Findings Cohort 1 included 265 adults and 387 children (125 aged 12–17 years, 130 aged 4–11 years, and 132 aged 1–3 years at the time of dose 1 vaccination). In the long-term follow-up period, 30 SAEs were reported in cohort 1, none considered related to the Ebola vaccine regimen. The child in cohort 2 completed the study without any SAEs. In adults vaccinated with the two-dose regimen, the binding antibody geometric mean concentration (GMC) five years post-dose 1 was 394 EU/mL (95% CI: 290; 536), with 61% considered vaccine responders. Adults who had received an additional Ad26.ZEBOV booster in the previous trial had an eight-fold higher GMC (3003 EU/mL, 95% CI: 2126; 4243), with 96% responders, compared with those who did not receive a booster. In children vaccinated with the two-dose regimen, GMCs of binding antibodies at four years post-dose 1 were 379 EU/mL (95% CI: 296; 486) in the 12–17-year age group, 414 EU/mL (95% CI: 323; 532) in the 4–11-year age group, and 694 EU/mL (95% CI: 553; 872) in the 1–3-year age group, with responder rates of 66%, 77%, and 91%, respectively. Interpretation The Ad26.ZEBOV, MVA-BN-Filo regimen demonstrated long-term safety and immunogenicity. Booster doses enhanced long-term immunogenicity, supporting their role in vaccination strategies. Funding Innovative Medicines Initiative 2 Joint Undertaking.