Single-dose VSV-Sudan virus vaccine protects macaques from lethal Sudan virus infection within one week

Uganda’s most recent Sudan virus (SUDV) outbreak created a public health emergency in Uganda and the Eastern Africa region. Currently, there are licensed countermeasures for Ebola virus (EBOV); however, there are no licensed vaccines or therapeutics against SUDV.We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein as the viral antigen. Cynomolgus macaques were vaccinated with a single intramuscular (IM) dose of VSV-SUDV either one month or one week prior to SUDV challenge. A third group was vaccinated with a single IM dose of VSV-EBOV one month prior to SUDV challenge to assess its cross-protective potential since SUDV and EBOV are related filoviruses. All vaccinated nonhuman primates (NHPs) developed antigen-specific IgG within 2 weeks of vaccination, including cross-reactive responses as demonstrated by ELISA. After IM challenge with a lethal dose of SUDV, all VSV-SUDV-vaccinated NHPs were uniformly protected from disease. In contrast, the VSV-EBOV-vaccinated and control NHPs succumbed to disease between day 5 and 7 after challenge presenting with classical signs of Sudan virus disease associated with high titer viremia, high viral organ load, dysregulated cytokine profiles and typical pathological changes. The humoral immune response in the NHPs vaccinated with VSV-SUDV one month before challenge resulted in a profound and sustained antibody response with a diverse functionality profile which was not observed to the same extend in NHPs vaccinated one week before challenge.Taken together, we demonstrated that VSV-EBOV provided no relevant protection against SUDV infection in NHPs highlighting the need for species-specific vaccines against filoviruses. Furthermore, our data show that VSV-SUDV is a fast-acting single-dose vaccine ideal for use in future outbreaks.