Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA
Focusing T cell responses on the most vulnerable parts of HIV-1, the functionally conserved regions of HIV-1 proteins, is likely a key prerequisite for vaccine success. For a T cell vaccine to efficiently control HIV-1 replication, the vaccine-elicited individual CD8+ T cells and as a population hav...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-03-01
|
| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050118301062 |
| _version_ | 1828498149869617152 |
|---|---|
| author | Nathifa Moyo Annette B. Vogel Søren Buus Stephanie Erbar Edmund G. Wee Ugur Sahin Tomáš Hanke |
| author_facet | Nathifa Moyo Annette B. Vogel Søren Buus Stephanie Erbar Edmund G. Wee Ugur Sahin Tomáš Hanke |
| author_sort | Nathifa Moyo |
| collection | DOAJ |
| description | Focusing T cell responses on the most vulnerable parts of HIV-1, the functionally conserved regions of HIV-1 proteins, is likely a key prerequisite for vaccine success. For a T cell vaccine to efficiently control HIV-1 replication, the vaccine-elicited individual CD8+ T cells and as a population have to display a number of critical traits. If any one of these traits is suboptimal, the vaccine is likely to fail. Fine-tuning of individual protective characteristics of T cells will require iterative stepwise improvements in clinical trials. Although the second-generation tHIVconsvX immunogens direct CD8+ T cells to predominantly protective and conserved epitopes, in the present work, we have used formulated self-amplifying mRNA (saRNA) to deliver tHIVconsvX to the immune system. We demonstrated in BALB/c and outbred mice that regimens employing saRNA vaccines induced broadly specific, plurifunctional CD8+ and CD4+ T cells, which displayed structured memory subpopulations and were maintained at relatively high frequencies over at least 22 weeks post-administration. This is one of the first thorough analyses of mRNA vaccine-elicited T cell responses. The combination of tHIVconsvX immunogens and the highly versatile and easily manufacturable saRNA platform may provide a long-awaited opportunity to define and optimize induction of truly protective CD8+ T cell parameters in human volunteers. Keywords: RNA vaccine, HIV vaccine, conserved regions, tHIVconsvX, simian adenovirus, MVA, T cell vaccine, heterologous prime-boost, in vivo killing, T cells |
| first_indexed | 2024-12-11T13:01:38Z |
| format | Article |
| id | doaj.art-4001d86cb5264b179c093c665745d71f |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-11T13:01:38Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-4001d86cb5264b179c093c665745d71f2022-12-22T01:06:27ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012019-03-01123246Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNANathifa Moyo0Annette B. Vogel1Søren Buus2Stephanie Erbar3Edmund G. Wee4Ugur Sahin5Tomáš Hanke6The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UKBiopharmaceutical New Technologies (BioNTech) Corporation, Mainz 55131, GermanyDepartment of Immunology and Microbiology, University of Copenhagen, Copenhagen 2200, DenmarkBiopharmaceutical New Technologies (BioNTech) Corporation, Mainz 55131, GermanyThe Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UKBiopharmaceutical New Technologies (BioNTech) Corporation, Mainz 55131, GermanyThe Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan; Corresponding author: Tomáš Hanke, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.Focusing T cell responses on the most vulnerable parts of HIV-1, the functionally conserved regions of HIV-1 proteins, is likely a key prerequisite for vaccine success. For a T cell vaccine to efficiently control HIV-1 replication, the vaccine-elicited individual CD8+ T cells and as a population have to display a number of critical traits. If any one of these traits is suboptimal, the vaccine is likely to fail. Fine-tuning of individual protective characteristics of T cells will require iterative stepwise improvements in clinical trials. Although the second-generation tHIVconsvX immunogens direct CD8+ T cells to predominantly protective and conserved epitopes, in the present work, we have used formulated self-amplifying mRNA (saRNA) to deliver tHIVconsvX to the immune system. We demonstrated in BALB/c and outbred mice that regimens employing saRNA vaccines induced broadly specific, plurifunctional CD8+ and CD4+ T cells, which displayed structured memory subpopulations and were maintained at relatively high frequencies over at least 22 weeks post-administration. This is one of the first thorough analyses of mRNA vaccine-elicited T cell responses. The combination of tHIVconsvX immunogens and the highly versatile and easily manufacturable saRNA platform may provide a long-awaited opportunity to define and optimize induction of truly protective CD8+ T cell parameters in human volunteers. Keywords: RNA vaccine, HIV vaccine, conserved regions, tHIVconsvX, simian adenovirus, MVA, T cell vaccine, heterologous prime-boost, in vivo killing, T cellshttp://www.sciencedirect.com/science/article/pii/S2329050118301062 |
| spellingShingle | Nathifa Moyo Annette B. Vogel Søren Buus Stephanie Erbar Edmund G. Wee Ugur Sahin Tomáš Hanke Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA Molecular Therapy: Methods & Clinical Development |
| title | Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA |
| title_full | Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA |
| title_fullStr | Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA |
| title_full_unstemmed | Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA |
| title_short | Efficient Induction of T Cells against Conserved HIV-1 Regions by Mosaic Vaccines Delivered as Self-Amplifying mRNA |
| title_sort | efficient induction of t cells against conserved hiv 1 regions by mosaic vaccines delivered as self amplifying mrna |
| url | http://www.sciencedirect.com/science/article/pii/S2329050118301062 |
| work_keys_str_mv | AT nathifamoyo efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna AT annettebvogel efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna AT sørenbuus efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna AT stephanieerbar efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna AT edmundgwee efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna AT ugursahin efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna AT tomashanke efficientinductionoftcellsagainstconservedhiv1regionsbymosaicvaccinesdeliveredasselfamplifyingmrna |