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Published on: November 1, 2011
Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine
Kyle L O'Donnell1, Friederike Feldmann2, Benjamin Kaza1
1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
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.
Insights
A novel vesicular stomatitis virus (VSV)-based Marburg virus (MARV) vaccine candidate, VSV-MARV, demonstrated uniform protection in macaques with reduced doses. This fast-acting vaccine shows promise for emergency outbreak response.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Marburg virus disease (MVD) is a severe hemorrhagic fever with high fatality rates, posing a significant global health threat.
- Current treatment and vaccine options for MVD are limited, necessitating the development of effective countermeasures.
- Recent outbreaks in Guinea and Ghana underscore the urgent need for rapid-response Marburg virus vaccines.
Purpose of the Study:
- To evaluate the protective efficacy and immunogenicity of a reduced-dose vesicular stomatitis virus (VSV)-based Marburg virus (MARV) vaccine (VSV-MARV).
- To determine if lower vaccine doses administered at different time points before challenge can elicit protective immunity against Marburg virus.
- To investigate the immune responses, including humoral and cellular immunity, induced by the VSV-MARV vaccine.
Main Methods:
- Cynomolgus macaques were vaccinated with reduced doses (1 × 105 or 1 × 103 PFU) of VSV-MARV 14 or 7 days before Marburg virus challenge.
- Humoral immune responses, including antigen-specific IgG, neutralizing antibodies, and antibody-dependent cellular phagocytosis (ADCP), were assessed.
- Cellular immune responses, focusing on NK cell activation and antigen-specific memory T cell subsets, were analyzed post-vaccination.
Main Results:
- All vaccinated macaques exhibited uniform protection against Marburg virus challenge, with no detectable viremia.
- Vaccination with VSV-MARV induced sustained antigen-specific IgG responses and significant neutralizing antibody titers.
- Evidence of NK cell activation and antigen-specific memory T cell responses indicated a robust cellular immune component alongside the primary humoral response.
Conclusions:
- The VSV-MARV vaccine candidate provides rapid and complete protection in a non-human primate model at reduced doses.
- The vaccine elicits both humoral and cellular immune responses, contributing to its protective efficacy.
- VSV-MARV is a promising candidate for clinical development as a fast-acting vaccine for Marburg virus emergency situations.
