Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus
Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in haemorrhagic disease and high case fatality rates (>40%) in humans. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatit...
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2252513 |
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| author | Cecilia A. Prator Brianna M. Dorratt Kyle L. O’Donnell Justin Lack Amanda N. Pinski Stacy Ricklefs Craig A. Martens Ilhem Messaoudi Andrea Marzi |
| author_facet | Cecilia A. Prator Brianna M. Dorratt Kyle L. O’Donnell Justin Lack Amanda N. Pinski Stacy Ricklefs Craig A. Martens Ilhem Messaoudi Andrea Marzi |
| author_sort | Cecilia A. Prator |
| collection | DOAJ |
| description | Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in haemorrhagic disease and high case fatality rates (>40%) in humans. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development. Previously, a single 10 million PFU dose of VSV-MARV administered 1–5 weeks before lethal MARV challenge conferred uniform protection in nonhuman primates (NHPs), demonstrating fast-acting potential. Additionally, our group recently demonstrated that even a low dose VSV-MARV (1000 PFU) protected NHPs when given 7 days before MARV challenge. In this study, we longitudinally profiled the transcriptional responses of NHPs vaccinated with this low dose of VSV-MARV either 14 or 7 days before lethal MARV challenge. NHPs vaccinated 14 days before challenge presented with transcriptional changes consistent with an antiviral response before challenge. Limited gene expression changes were observed in the group vaccinated 7 days before challenge. After challenge, genes related to lymphocyte-mediated immunity were only observed in the group vaccinated 14 days before challenge, indicating that the length of time between vaccination and challenge influenced gene expression. Our results indicate that a low dose VSV-MARV elicits distinct immune responses that correlate with protection against MVD. A low dose of VSV-MARV should be evaluated in clinical rails as it may be an option to deliver beneficial public health outcomes to more people in the event of future outbreaks. |
| format | Article |
| id | doaj-art-5371d694e1424ff28dffc153b83eba32 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-5371d694e1424ff28dffc153b83eba322025-08-20T03:28:50ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112210.1080/22221751.2023.2252513Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virusCecilia A. Prator0Brianna M. Dorratt1Kyle L. O’Donnell2Justin Lack3Amanda N. Pinski4Stacy Ricklefs5Craig A. Martens6Ilhem Messaoudi7Andrea Marzi8Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USADepartment of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USANIAID Collaborative Bioinformatics Resource (NCBR), National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USADepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USAResearch Technology Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USAResearch Technology Branch, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USADepartment of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USAInfection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in haemorrhagic disease and high case fatality rates (>40%) in humans. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development. Previously, a single 10 million PFU dose of VSV-MARV administered 1–5 weeks before lethal MARV challenge conferred uniform protection in nonhuman primates (NHPs), demonstrating fast-acting potential. Additionally, our group recently demonstrated that even a low dose VSV-MARV (1000 PFU) protected NHPs when given 7 days before MARV challenge. In this study, we longitudinally profiled the transcriptional responses of NHPs vaccinated with this low dose of VSV-MARV either 14 or 7 days before lethal MARV challenge. NHPs vaccinated 14 days before challenge presented with transcriptional changes consistent with an antiviral response before challenge. Limited gene expression changes were observed in the group vaccinated 7 days before challenge. After challenge, genes related to lymphocyte-mediated immunity were only observed in the group vaccinated 14 days before challenge, indicating that the length of time between vaccination and challenge influenced gene expression. Our results indicate that a low dose VSV-MARV elicits distinct immune responses that correlate with protection against MVD. A low dose of VSV-MARV should be evaluated in clinical rails as it may be an option to deliver beneficial public health outcomes to more people in the event of future outbreaks.https://www.tandfonline.com/doi/10.1080/22221751.2023.2252513FilovirusMarburg virus AngolaMARVvesicular stomatitis virusnonhuman primatehost response |
| spellingShingle | Cecilia A. Prator Brianna M. Dorratt Kyle L. O’Donnell Justin Lack Amanda N. Pinski Stacy Ricklefs Craig A. Martens Ilhem Messaoudi Andrea Marzi Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus Emerging Microbes and Infections Filovirus Marburg virus Angola MARV vesicular stomatitis virus nonhuman primate host response |
| title | Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus |
| title_full | Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus |
| title_fullStr | Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus |
| title_full_unstemmed | Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus |
| title_short | Transcriptional profiling of immune responses in NHPs after low-dose, VSV-based vaccination against Marburg virus |
| title_sort | transcriptional profiling of immune responses in nhps after low dose vsv based vaccination against marburg virus |
| topic | Filovirus Marburg virus Angola MARV vesicular stomatitis virus nonhuman primate host response |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2252513 |
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