VSV-based vaccine provides species-specific protection against Sudan virus challenge in macaques

The ongoing Sudan virus (SUDV) outbreak in Uganda highlights the need for rapid response capabilities against emerging viruses with high public health impact. While such countermeasures have been established for Ebola virus (EBOV), they unfortunately do not exist for SUDV or any other human-pathogenic filovirus. Here, we describe the generation and characterization of the vesicular stomatitis virus (VSV)-based vaccine VSV-SUDV and demonstrate the protective efficacy following a single-dose vaccination against lethal SUDV infection in nonhuman primates (NHPs). As we repurposed NHPs from a successful VSV-EBOV vaccine efficacy study, we further demonstrate that VSV-SUDV can be used effectively in individuals previously vaccinated against EBOV. While the NHPs developed cross-reactive humoral responses to SUDV after VSV-EBOV vaccination and EBOV challenge, cross-protection was limited emphasizing the need for the development of specific countermeasures for each human-pathogenic ebolavirus. Additionally, our data provides evidence that while previous VSV-EBOV immunity is boosted after VSV-SUDV vaccination, it has only limited impact on the immunogenicity and protective efficacy of VSV-SUDV vaccination important for frontline outbreak workers.