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

Abstract

BACKGROUND:

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 1 × 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 × 105 or 1 × 103 PFU 14 days or 1 × 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.

• Authors: Kyle L O'Donnell, Friederike Feldmann, Benjamin Kaza, Chad S Clancy, Patrick W Hanley, Paige Fletcher, Andrea Marzi
• Journal: EBioMedicine (EBioMedicine) Vol. 89 Pg. 104463 (Mar 2023) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 36774693 (Publication Type: Journal Article)
• Copyright: Published by Elsevier B.V.

Chemical References

• Viral Vaccines
• Antibodies, Neutralizing

Topics

• Animals
• Humans
• Marburg Virus Disease (prevention & control)
• Viral Vaccines
• Macaca fascicularis
• Vaccination
• Antibodies, Neutralizing