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

Background Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD) which has a case fatality rate up to similar 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 1 x 107 plaque-forming units (PFU) administered 7 days before challenge resulted in uniform protection from disease in cynomolgus macaques.Methods As we sought to lower the vaccination dose to achieve a higher number of vaccine doses per vial, we administered 1 x 105 or 1 x 103 PFU 14 days or 1 x 103 PFU 7 days before challenge to cohorts of cynomolgus macaques and investigated immunity as well as protective efficacy.Results 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. The cellular response after vaccination was characterized by an 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.Interpretation 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.Funding This work was funded by the Intramural Research Program NIAID, NIH.Copyright Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Marburg virus (MARV) is a highly pathogenic agent with no available treatments or vaccines. This study demonstrates that a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV-Angola glycoprotein has a potential as a viable and fast-acting MARV vaccine candidate, providing uniform protection against the virus when administered in lower doses.