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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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Official URL: https://doi.org/10.1038/s41598-017-13331-1

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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
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
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:
DateEvent
12 October 2017Published
1 January 2017Accepted
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:
Project/Grant IDRIOXX Funder NameFunder ID
CUTHIVAC 241904Seventh Framework Programmehttp://dx.doi.org/10.13039/100011102
083844/z/07/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
UNSPECIFIED[NIHR] National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
MRC_UU_12023/23[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265

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