Haidari, G;
Day, S;
Wood, M;
Ridgers, H;
Cope, A;
Fleck, S;
Yan, C;
... Shattock, RJ; + view all
(2019)
The Safety and Immunogenicity of GTU (R) MultiHIV DNA Vaccine Delivered by Transcutaneous and Intramuscular Injection With or Without Electroporation in HIV-1 Positive Subjects on Suppressive ART.
Frontiers in Immunology
, 10
, Article 2911. 10.3389/fimmu.2019.02911.
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Abstract
Previous studies have shown targeting different tissues via the transcutaneous (TC) and intramuscular injection (IM) with or without electroporation (EP) has the potential to trigger immune responses to DNA vaccination. The CUTHIVTHER 001 Phase I/II randomized controlled clinical trial was designed to determine whether the mode of DNA vaccination delivery (TC+IM or EP+IM) could influence the quality and function of induced cellular immune responses compared to placebo, in an HIV positive clade B cohort on antiretroviral therapy (ART). The GTU®MultiHIV B DNA vaccine DNA vaccine encoded a MultiHIV B clade fusion protein to target the cellular response. Overall the vaccine and regimens were safe and well-tolerated. There were robust pre-vaccination IFN-g responses with nomeasurable change following vaccination compared to placebo. However, modest intracellular cytokine staining (ICS) responses were seen in the TC+IM group. A high proportion of individuals demonstrated potent viral inhibition at baseline that was not improved by vaccination. These results show that HIV positive subjects with nadir CD4+ counts ≥250 on suppressive ART display potent levels of cellular immunity and viral inhibition, and that DNA vaccination alone is insufficient to improve such responses. These data suggest that more potent prime-boost vaccination strategies are likely needed to improve pre-existing responses in similar HIV-1 cohorts (This study has been registered at http://ClinicalTrials.gov under registration no. NCT02457689).
| Type: | Article |
|---|---|
| Title: | The Safety and Immunogenicity of GTU (R) MultiHIV DNA Vaccine Delivered by Transcutaneous and Intramuscular Injection With or Without Electroporation in HIV-1 Positive Subjects on Suppressive ART |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2019.02911 |
| Publisher version: | https://doi.org/10.3389/fimmu.2019.02911 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, HIV-1, therapeutic vaccine, electroporation, transcutaneous, plasmid DNA, ASSAY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > VP: Health UCL > Provost and Vice Provost Offices > VP: Health > Translational Research Office |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10089451 |
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