| Autor: |
Kyle L. O'Donnell, Friederike Feldmann, Benjamin Kaza, Chad S. Clancy, Patrick W. Hanley, Paige Fletcher, Andrea Marzi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 89, Iss , Pp 104463- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2023.104463 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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