Fast-acting single-dose vesicular stomatitis virus-Sudan virus vaccine: a challenge study in macaques.

Abstract

The Sudan virus (SUDV) outbreaks in recent years, including the most recent outbreak in Uganda, created a public health emergency in the eastern Africa region. There are no licensed vaccines or therapeutics approved against SUDV; however, we have previously developed a vesicular stomatitis virus (VSV)-based vaccine expressing the SUDV glycoprotein and showed its single-dose efficacy in non-human primates (NHPs) with pre-existing Ebola virus (EBOV) immunity. Here, we determined the fast-acting capacity of this vaccine in naive NHPs. In addition, we examined if the licensed VSV-EBOV vaccine would provide any prophylactic benefit against SUDV infection. We used four groups of male cynomolgus macaques (n=6 per group) aged 2·5-4·5 years and weighing 2·9-5·2 kg. NHPs were vaccinated by intramuscular injection 28 days before challenge with either 1 × 10⁷ plaque-forming units (PFUs) VSV-SUDV, VSV-EBOV, or control vaccine (VSV-LASV). Another group was vaccinated with 1 × 10⁷ PFU VSV-SUDV 7 days before challenge. On day 0, all 24 NHPs were challenged with a lethal dose of SUDV (1 × 10⁴ 50% tissue culture infectious doses [TCID₅₀] SUDV-Gulu, backtitred as 1·1 × 10⁴ TCID₅₀). We assessed anaesthetised NHPs on days -28, -21, -14, and -7 before challenge; days 0, 3, 6, 9, 14, 21, 28, and 35 after challenge; and at euthanasia (day 42 for survivors). All VSV-SUDV-vaccinated NHPs were protected from disease after the lethal SUDV challenge. In contrast, the VSV-EBOV-vaccinated and control NHPs succumbed to disease between days 5 and 7 after challenge presenting with classical signs of Sudan virus disease associated with high-titre viraemia (>1 × 10⁸ TCID₅₀ per mL), high viral organ load (>1 × 10⁸ TCID₅₀ per g), dysregulated cytokine profiles, and typical pathological changes. The humoral immune response in the NHPs vaccinated with VSV-SUDV 1 month before challenge resulted in a profound and sustained serum antibody response (20 000-30 000 U/mL) with a diverse functionality profile (antibody-dependent cellular phagocytosis and antibody-dependent complement), which was not observed to the same extent in NHPs vaccinated 1 week before challenge. We showed that a single dose of VSV-SUDV protected NHPs from lethal SUDV infection within 1 week. The fast-acting nature highlights VSV-SUDV as an ideal countermeasure for ring vaccination during outbreaks of Sudan virus disease pending further preclinical and clinical assessment. In contrast, VSV-EBOV provided no relevant protection against SUDV infection in NHPs, highlighting the need for species-specific filovirus vaccines. National Institutes of Health, US Department of Health and Human Services.