The Lancet. Microbe · 2025
Fast-acting single-dose vesicular stomatitis virus-Sudan virus vaccine: a challenge study in macaques.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Fletcher Paige, O'Donnell Kyle L, Feldmann Friederike, Rhoderick Joseph F, Clancy Chad S, Haase Jil A, Prator Cecilia A, Smith Brian J, Gunn Bronwyn M, Feldmann Heinz, Marzi Andrea
Аннотация
BACKGROUND: 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.
METHODS: 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).
FINDINGS: 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.
INTERPRETATION: 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.
FUNDING: National Institutes of Health, US Department of Health and Human Services.
METHODS: 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).
FINDINGS: 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.
INTERPRETATION: 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.
FUNDING: National Institutes of Health, US Department of Health and Human Services.