Predicting the efficacy of Ervebo against Bundibugyo virus disease

There is currently no clinical data for the effectiveness of the only licensed Ebola virus disease vaccine (Ervebo) against Bundibugyo virus disease. A number of studies have shown immune cross-reactivity with Bundibugyo virus after Ervebo vaccination. However, antibody recognition of Bundibugyo is around 2.8-fold lower than recognition of Ebola virus. Here, we aimed to infer how a 2.8-fold drop in immune recognition may affect Ervebo protection against Bundibugyo virus disease based on analysis of data on Ervebo immunogenicity and protection from Ebola virus disease. This work has three main components. Firstly, we analysed the timing of vaccine protection in the Ervebo pivotal ring vaccination clinical trial. Secondly, we performed a systematic review and meta-analysis of antibody responses to Ebola virus after Ervebo vaccination over time. Thirdly, we combined these data with previously reported data on the cross-reactivity to Bundibugyo virus to infer protection of Ervebo against Bundibugyo virus disease. We find that the clinical trial data for Ervebo supports vaccine protection beginning earlier than 10 days after vaccination. Secondly, binding antibody levels against Ebola virus on day 28 post vaccination (peak responses) were on average 12.9-fold (95% confidence interval, CI: 6.4 - 26.0) higher than on day 7, 6.3-fold (95% CI: 3.7 -10.8) higher than on day 10, and 2.5-fold (95% CI: 1.4 - 4.4) higher than on day 14 (neutralising antibodies showed similar results). Finally, we consider the scenarios where antibody levels to Ebola virus at day 7 or 10 are putative protective thresholds against Ebola virus disease, and we assume these thresholds also apply for Bundibugyo virus disease. Then, with a 2.8-fold reduction of responses to Bundibugyo compared to Ebola virus, we predict antibody responses to Bundibugyo virus after Ervebo vaccination are likely above these putative protective thresholds.