Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania

BACKGROUND:Ebola vaccine development was accelerated in response to the 2014 Ebola virus outbreak. This Phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous prime-boost Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malarial-endemic settings. METHODS:Healthy volunteers aged 18-50 years from Tanzania (n=25) and Uganda (n=47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (prime vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV, respectively (boost vaccination), with intervals of 28 or 56 days. RESULTS:72 adults were randomized to receive vaccination (N=60) or placebo (N=12). No vaccine-related serious adverse events (AEs) were reported. The most frequent solicited local and systemic AEs were injection site pain (frequency 70%, 66% and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV and placebo, respectively) and headache (57%, 56% and 46%, respectively). AE patterns were similar among regimens. At 21 days post boost, 100% of volunteers demonstrated binding antibody responses against EBOV glycoprotein and 87-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV priming induced more robust initial binding antibody and cellular responses than MVA-BN-Filo priming. CONCLUSIONS:Heterologous prime-boost vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola is well tolerated and immunogenic in healthy volunteers.