T-cell responses induced in normal volunteers immunized with a DNA-based vaccine containing HIV-1 env and rev

RR MacGregor, R Ginsberg, KE Ugen, Y Baine… - Aids, 2002 - journals.lww.com
RR MacGregor, R Ginsberg, KE Ugen, Y Baine, CU Kang, XM Tu, T Higgins, DB Weiner…
Aids, 2002journals.lww.com
Objective: An effective HIV-1 vaccine will likely need to induce strong cell-mediated
immunity in humans. Therefore, we examined the ability of a DNA HIV-1 vaccine to induce a
T-cell response in HIV-1 seronegative humans. Design: Individuals were enrolled in a phase
I clinical trial of safety and immune responses to an env/rev-containing plasmid at doses of
100, 300 or 1000 μg. Peripheral blood mononuclear cells (PBMC) samples were analyzed
by standard lymphocyte proliferation, cytotoxic T lymphocyte (CTL) and ELISPOT …
Abstract
Objective:
An effective HIV-1 vaccine will likely need to induce strong cell-mediated immunity in humans. Therefore, we examined the ability of a DNA HIV-1 vaccine to induce a T-cell response in HIV-1 seronegative humans.
Design:
Individuals were enrolled in a phase I clinical trial of safety and immune responses to an env/rev-containing plasmid at doses of 100, 300 or 1000 μg. Peripheral blood mononuclear cells (PBMC) samples were analyzed by standard lymphocyte proliferation, cytotoxic T lymphocyte (CTL) and ELISPOT techniques.
Results:
PBMCs from subjects immunized with doses as low as 300 μg proliferated in vitro to env (four of six) or rev (three of six) proteins. Importantly, when the dose of vaccine was increased to 1000 μg of DNA, lymphocytes secreted IFN-gamma in an ELISPOT assay following in vitro stimulation with env (three of six) or rev (four of six) proteins.
Conclusion:
We observed HIV-1 DNA plasmid vaccines induce CD4 T-helper cell responses in humans. We observed a discrepancy in the CD4 versus CD8 response suggesting the importance of analyzing both compartments in clinical evaluation. Furthermore, this report demonstrates the high level of immunogenicity of rev and its importance as a component of a prophylactic vaccine for HIV-1.
Lippincott Williams & Wilkins