Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine
Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo<sup>®</sup>), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/2/67 |
| _version_ | 1797409447088226304 |
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| author | Francesco Santoro Alessia Donato Simone Lucchesi Sara Sorgi Alice Gerlini Marielle C. Haks Tom H. M. Ottenhoff Patricia Gonzalez-Dias VSV-EBOVAC Consortium VSV-EBOPLUS Consortium Helder I. Nakaya Angela Huttner Claire-Anne Siegrist Donata Medaglini Gianni Pozzi |
| author_facet | Francesco Santoro Alessia Donato Simone Lucchesi Sara Sorgi Alice Gerlini Marielle C. Haks Tom H. M. Ottenhoff Patricia Gonzalez-Dias VSV-EBOVAC Consortium VSV-EBOPLUS Consortium Helder I. Nakaya Angela Huttner Claire-Anne Siegrist Donata Medaglini Gianni Pozzi |
| author_sort | Francesco Santoro |
| collection | DOAJ |
| description | Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo<sup>®</sup>), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific “blood transcription modules” (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres. |
| first_indexed | 2024-03-09T04:14:40Z |
| format | Article |
| id | doaj.art-0cc37b3556264c92acdea5514faf43ff |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T04:14:40Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-0cc37b3556264c92acdea5514faf43ff2023-12-03T13:55:46ZengMDPI AGVaccines2076-393X2021-01-01926710.3390/vaccines9020067Human Transcriptomic Response to the VSV-Vectored Ebola VaccineFrancesco Santoro0Alessia Donato1Simone Lucchesi2Sara Sorgi3Alice Gerlini4Marielle C. Haks5Tom H. M. Ottenhoff6Patricia Gonzalez-Dias7VSV-EBOVAC ConsortiumVSV-EBOPLUS ConsortiumHelder I. Nakaya8Angela Huttner9Claire-Anne Siegrist10Donata Medaglini11Gianni Pozzi12Laboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyMicrobiotec srl, 53100 Siena, ItalyDepartment of Infectious Diseases, Leiden University Medical Center, 2333 Leiden, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, 2333 Leiden, The NetherlandsDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-020, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-020, BrazilDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1211 Geneva, SwitzerlandLaboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, ItalyEbolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo<sup>®</sup>), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific “blood transcription modules” (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres.https://www.mdpi.com/2076-393X/9/2/67Ebolavirus Diseasetranscriptomicsrecombinant VSVVSV-ZEBOVvaccinelive viral vector |
| spellingShingle | Francesco Santoro Alessia Donato Simone Lucchesi Sara Sorgi Alice Gerlini Marielle C. Haks Tom H. M. Ottenhoff Patricia Gonzalez-Dias VSV-EBOVAC Consortium VSV-EBOPLUS Consortium Helder I. Nakaya Angela Huttner Claire-Anne Siegrist Donata Medaglini Gianni Pozzi Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine Vaccines Ebolavirus Disease transcriptomics recombinant VSV VSV-ZEBOV vaccine live viral vector |
| title | Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine |
| title_full | Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine |
| title_fullStr | Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine |
| title_full_unstemmed | Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine |
| title_short | Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine |
| title_sort | human transcriptomic response to the vsv vectored ebola vaccine |
| topic | Ebolavirus Disease transcriptomics recombinant VSV VSV-ZEBOV vaccine live viral vector |
| url | https://www.mdpi.com/2076-393X/9/2/67 |
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