Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures.
Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defect...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009215 |
| _version_ | 1818348774410420224 |
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| author | Jessamine E Hazlewood Troy Dumenil Thuy T Le Andrii Slonchak Stephen H Kazakoff Ann-Marie Patch Lesley-Ann Gray Paul M Howley Liang Liu John D Hayball Kexin Yan Daniel J Rawle Natalie A Prow Andreas Suhrbier |
| author_facet | Jessamine E Hazlewood Troy Dumenil Thuy T Le Andrii Slonchak Stephen H Kazakoff Ann-Marie Patch Lesley-Ann Gray Paul M Howley Liang Liu John D Hayball Kexin Yan Daniel J Rawle Natalie A Prow Andreas Suhrbier |
| author_sort | Jessamine E Hazlewood |
| collection | DOAJ |
| description | Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such injection site vaccinology approaches should inform refinements in poxvirus-based vector design. |
| first_indexed | 2024-12-13T17:55:24Z |
| format | Article |
| id | doaj.art-51873aa015164c15b3f0332db477b26b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-13T17:55:24Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-51873aa015164c15b3f0332db477b26b2022-12-21T23:36:24ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-01-01171e100921510.1371/journal.ppat.1009215Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures.Jessamine E HazlewoodTroy DumenilThuy T LeAndrii SlonchakStephen H KazakoffAnn-Marie PatchLesley-Ann GrayPaul M HowleyLiang LiuJohn D HayballKexin YanDaniel J RawleNatalie A ProwAndreas SuhrbierPoxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such injection site vaccinology approaches should inform refinements in poxvirus-based vector design.https://doi.org/10.1371/journal.ppat.1009215 |
| spellingShingle | Jessamine E Hazlewood Troy Dumenil Thuy T Le Andrii Slonchak Stephen H Kazakoff Ann-Marie Patch Lesley-Ann Gray Paul M Howley Liang Liu John D Hayball Kexin Yan Daniel J Rawle Natalie A Prow Andreas Suhrbier Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. PLoS Pathogens |
| title | Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. |
| title_full | Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. |
| title_fullStr | Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. |
| title_full_unstemmed | Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. |
| title_short | Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures. |
| title_sort | injection site vaccinology of a recombinant vaccinia based vector reveals diverse innate immune signatures |
| url | https://doi.org/10.1371/journal.ppat.1009215 |
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