Single-dose VSV-Sudan virus vaccine protects from lethal Sudan virus infection within one week: a challenge study in macaques: VSV-SUDV but not VSV-EBOV protects NHPs from Sudan virus disease.

BACKGROUND: The Sudan virus (SUDV) outbreaks in recent years including the ongoing outbreak in Uganda created a public health emergency beyond the Eastern Africa region. Currently, there are licensed countermeasures for Ebola virus (EBOV); however, there are no licensed vaccines or therapeutics against SUDV. METHODS: We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein. Cynomolgus macaques were vaccinated intramuscularly with a single dose of VSV-SUDV either one month or one week prior to SUDV challenge. A third group was vaccinated with a single dose of VSV-EBOV one month prior to SUDV challenge to assess its cross-protective potential, and a control group received an unrelated VSV-based vaccine. RESULTS: All vaccinated nonhuman primates (NHPs) developed antigen-specific IgG within 2 weeks of vaccination, including cross-reactive responses. After 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. INTERPRETATION: We demonstrated that a single dose of VSV-SUDV protected NHPs from lethal SUDV infection within one week. The fast-acting nature makes VSV-SUDV an ideal countermeasure for ring vaccination during outbreaks of Sudan virus disease. In contrast, VSV-EBOV provided no relevant protection against SUDV infection in NHPs highlighting the need for species-specific filovirus vaccines.