Safety and Immunogenicity of Heterologous and Homologous Two Dose Regimens of Ad26- and MVA-Vectored Ebola Vaccines: A Randomized, Controlled Phase 1 Study.

Background This phase 1 placebo-controlled study assessed safety and immunogenicity of two-dose regimens of Ad26.ZEBOV (Ad26) and MVA-BN-Filo (MVA) vaccines with booster vaccination at Day 360. Methods Healthy US adults (N = 164) randomized into 10 groups received saline placebo, standard or high doses of Ad26 or MVA in two-dose regimens in 7-, 14-, 28-, or 56-day intervals; eight groups received booster Ad26 or MVA vaccinations on Day 360. Participants reported solicited and unsolicited reactogenicity; we measured IgG binding, neutralizing antibodies and cellular immune responses to Ebolavirus (EBOV) glycoprotein. Results All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA or MVA,Ad26) and homologous Ad26,Ad26 regimens induced humoral and cellular immune responses 21 days post-dose 2; responses were higher following heterologous regimens. Booster vaccination elicited anamnestic responses in all participants. Conclusions Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous two-dose Ad26,MVA regimens containing an EBOV insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the two-dose regimen.