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Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine
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. The...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947254/ https://www.ncbi.nlm.nih.gov/pubmed/36774693 http://dx.doi.org/10.1016/j.ebiom.2023.104463 |
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author | O'Donnell, Kyle L. Feldmann, Friederike Kaza, Benjamin Clancy, Chad S. Hanley, Patrick W. Fletcher, Paige Marzi, Andrea |
author_facet | O'Donnell, Kyle L. Feldmann, Friederike Kaza, Benjamin Clancy, Chad S. Hanley, Patrick W. Fletcher, Paige Marzi, Andrea |
author_sort | O'Donnell, Kyle L. |
collection | PubMed |
description | 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 × 10(7) 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 × 10(5) or 1 × 10(3) PFU 14 days or 1 × 10(3) 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 10.13039/100000060NIAID, 10.13039/100000002NIH. |
format | Online Article Text |
id | pubmed-9947254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99472542023-02-24 Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine O'Donnell, Kyle L. Feldmann, Friederike Kaza, Benjamin Clancy, Chad S. Hanley, Patrick W. Fletcher, Paige Marzi, Andrea eBioMedicine Articles 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 × 10(7) 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 × 10(5) or 1 × 10(3) PFU 14 days or 1 × 10(3) 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 10.13039/100000060NIAID, 10.13039/100000002NIH. Elsevier 2023-02-10 /pmc/articles/PMC9947254/ /pubmed/36774693 http://dx.doi.org/10.1016/j.ebiom.2023.104463 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles O'Donnell, Kyle L. Feldmann, Friederike Kaza, Benjamin Clancy, Chad S. Hanley, Patrick W. Fletcher, Paige Marzi, Andrea Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine |
title | Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine |
title_full | Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine |
title_fullStr | Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine |
title_full_unstemmed | Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine |
title_short | Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine |
title_sort | rapid protection of nonhuman primates against marburg virus disease using a single low-dose vsv-based vaccine |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9947254/ https://www.ncbi.nlm.nih.gov/pubmed/36774693 http://dx.doi.org/10.1016/j.ebiom.2023.104463 |
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