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-γ responses with no measurable 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).
Highlights
The development of safe and effective antiretroviral therapy (ART) has led to almost near normal life expectancy in people living with HIV, if diagnosed early and established on treatment [1]
The CUTHIVTHER 001 was a Phase I/II randomized controlled clinical trial to investigate the safety and immunogenicity of the GTU R MultiHIV B clade DNA vaccine administered 3 times in people living with clade B HIV infection who were stable on antiretroviral therapy (ART)
There was no clear trend overall which may be masked with the higher baseline levels of cytokines observed. In this Phase I/II randomized controlled clinical trial we aimed to determine whether the mode of DNA vaccination could influence the quality and function of induced cellular immune responses compared to placebo, in an HIV positive cohort on ART
Summary
The development of safe and effective antiretroviral therapy (ART) has led to almost near normal life expectancy in people living with HIV, if diagnosed early and established on treatment [1]. The rationale for the development of a therapeutic HIV1 vaccine is based on several immunological factors. These include the inability of natural infection with HIV to elicit sufficient immunity to control replication, HIV infection itself causing major abnormalities in the cellular immune response and the failure of ART to eradicate established infection [4]. Several combination strategies are currently in progress including the use of a vaccine plus latency reversal agent known as the “shock and kill” approach [6, 7], gene therapy with modification of CCR5 expression on target cells [8], and the use of broadly neutralizing antibodies to induce ART-free viral suppression [9]
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