Heterologous vaccination with a next-generation vaccinia virus and Ad26 induces Ebola-specific immunity in macaques

Different ways of combining virus vector-based vaccines can impact the effectiveness of immune responses against specific antigens. In this study, we explored the effects of different immunization schedules on immune responses elicited by viral vector-based vaccines in monkeys, with a focus on the heterologous regimens with a next-generation attenuated vaccinia virus, Sementis Copenhagen vector (SCV), and human adenovirus serotype 26 (Ad26) expressing the Ebola glycoprotein (EBOV-GP). Our findings highlight that the order of administration of these vaccines plays a pivotal role in modulating cellular immune responses. We observed that initiating immunization with Ad26.EBOV followed by SCV.EBOV, significantly enhanced the magnitude and quality of antigen-specific memory CD4+ T-cell responses when compared to a homologous Ad26.EBOV regimen. Importantly, the binding antibody titers induced by this heterologous approach were similar to that elicited by a homologous Ad26.EBOV regimen, although we observed a transiently elevated neutralizing antibody titers at the peak of the response for the SCV.EBOV/Ad26.EBOV regimen. Our results suggest that a heterologous vaccination strategy combining Ad26.EBOV and SCV.EBOV could be an alternative to the currently used Ad26/MVA platform for Ebola vaccination, potentially mitigating some of the manufacturing challenges associated with Modified Vaccinia virus Ankara (MVA). The observed benefits of the heterologous regimen, particularly its capacity to enhance T-cell responses, reinforce its potential as a promising alternative to homologous regimens that warrants further investigation.