Dataset Information

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.

SUBMITTER: O'Donnell KL

PROVIDER: S-EPMC9947254 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

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

O'Donnell Kyle L KL Feldmann Friederike F Kaza Benjamin B Clancy Chad S CS Hanley Patrick W PW Fletcher Paige P Marzi Andrea A

EBioMedicine 20230210

<h4>Background</h4>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. Prev ...[more]

PMID: 36774693

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Project description:The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSVDeltaG/SEBOVGP, VSVDeltaG/ZEBOVGP, and VSVDeltaG/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSVDeltaG/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species.

Dataset Information

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

Background

Methods

Results

Interpretation

Funding

Publications

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

Similar Datasets

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