Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine
Kyle L. O’Donnell, Friederike Feldmann, Benjamin Kaza, Chad S. Clancy, Patrick W. Hanley, Paige Fletcher, Andrea Marzi
Abstract
BACKGROUND: plaque-forming units (PFU) administered 7 days before challenge resulted in uniform protection from disease in cynomolgus macaques. METHODS: 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.