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Published: February 10, 2023
DOI: https://doi.org/10.1016/j.ebiom.2023.104463
Kyle L. O'Donnell, Friederike Feldmann, Benjamin Kaza, Chad S. Clancy, Patrick W. Hanley, Paige Fletcher, Andrea Marzi
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 × 107plaque-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.
https://www.thelancet.com/action/sho...2823%2900028-2
DOI: https://doi.org/10.1016/j.ebiom.2023.104463
Kyle L. O'Donnell, Friederike Feldmann, Benjamin Kaza, Chad S. Clancy, Patrick W. Hanley, Paige Fletcher, Andrea Marzi
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 × 107plaque-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.
https://www.thelancet.com/action/sho...2823%2900028-2