Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine

Abstract

Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD) which has a case fatality rate up to ~90% in humans. Recently, there were cases reported in Guinea and Ghana highlighting this virus as a high-consequence pathogen potentially threatening global public health. There are no licensed treatments or vaccines available today. We used a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV-Angola glycoprotein (VSV-MARV) as the viral antigen. Previously, a single dose of 1x107 plaque-forming units (PFU) administered 7 days before challenge resulted in uniform protection from disease in cynomolgus macaques. Here, we sought to lower the vaccination dose to allow for more doses per vial in an emergency outbreak situation. We administered 1x105 or 1x103 PFU 14 days before challenge and achieved uniform protection in both groups. When we administered 1x103 PFU 7 days before challenge, vaccination resulted in uniform protection with no detectable viremia. Antigen-specific IgG responses were induced by both vaccine concentrations and were sustained until the study endpoint. Neutralizing antibody responses and antibody-dependent cellular phagocytosis were observed with both vaccination doses and timelines. The cellular response after vaccination was characterized by early induction of NK cell activation. Additionally, antigen-specific memory T cell subsets were detected in all vaccination cohorts indicating that while the primary protective mechanism of VSV-MARV is the humoral response, a functional cellular response is also induced. Overall, this data highlights VSV-MARV as a viable and fast-acting MARV vaccine candidate suitable for deployment in emergency outbreak situations and supports its clinical development. One Sentence SummaryA single low dose of VSV-MARV administered 14 or 7 days before challenge protects NHPs uniformly from lethal disease.