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Combined skin and muscle vaccination differentially impact the quality of effector T cell functions : the CUTHIVAC-001 randomized trial
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Haidari, G., Cope, A., Miller, A., Venables, S., Yan, C., Ridgers, H., Reijonen, K., Hannaman, D., Spentzou, A., Hayes, P., Bouliotis, Georgios, Vogt, A., Joseph, S., Combadiere, B., McCormack, S. and Shattock, R. J. (2017) Combined skin and muscle vaccination differentially impact the quality of effector T cell functions : the CUTHIVAC-001 randomized trial. Scientific Reports, 7 (1). 13011. doi:10.1038/s41598-017-13331-1
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WRAP-combined-skin-muscle-vaccination-differentially-impact-quality-effector-T-cell-functions-Bouliotis-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1574Kb) | Preview |
Official URL: https://doi.org/10.1038/s41598-017-13331-1
Abstract
Targeting of different tissues via transcutaneous (TC), intradermal (ID) and intramuscular (IM) injection has the potential to tailor the immune response to DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1 negative volunteers we investigate whether the site and mode of DNA vaccination influences the quality of the cellular immune responses. We adopted a strategy of concurrent immunization combining IM injection with either ID or TC administration. As a third arm we assessed the response to IM injection administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B clade fusion protein designed to induce cellular immunity. The vaccine and regimens were well tolerated. We observed differential shaping of vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM + EP promoted strong IFN-γ responses and potent viral inhibition. ID + IM without EP resulted in a similar pattern of response but of lower magnitude. By contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated phenotype, associated with mucosal and epidermal protection. Whilst preliminary, these results offer new perspectives for differential shaping of desired cellular immunity required to fight the wide range of complex and diverse infectious diseases and cancers.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QR Microbiology | |||||||||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Cellular immunity, DNA vaccines, Antigen presenting cells | |||||||||||||||
| Journal or Publication Title: | Scientific Reports | |||||||||||||||
| Publisher: | Nature Publishing Group | |||||||||||||||
| ISSN: | 2045-2322 | |||||||||||||||
| Official Date: | 12 October 2017 | |||||||||||||||
| Dates: |
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| Date of first compliant deposit: | 10 October 2019 | |||||||||||||||
| Volume: | 7 | |||||||||||||||
| Number: | 1 | |||||||||||||||
| Article Number: | 13011 | |||||||||||||||
| DOI: | 10.1038/s41598-017-13331-1 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access | |||||||||||||||
| RIOXX Funder/Project Grant: |
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