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


METHODS
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 microg. 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 microg proliferated in vitro to env (four of six) or (three of six) proteins. Importantly, when the dose of vaccine was increased to 1000 microg 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.


CONCLUSIONS
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 and its importance as a component of a prophylactic vaccine for HIV-1.
MacGregor
Rob Roy
RR
Infectious Diseases Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Ginsberg
Richard
R
Ugen
Kenneth E
KE
Baine
Yaela
Y
Kang
Christina U
CU
Tu
Xin M
XM
Higgins
Terry
T
Weiner
David B
DB
Boyer
Jean D
JD
D016915:AIDS Vaccines / Q000276:immunology; D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env; D015694:Gene Products, rev; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015686:Gene Products, env; D015694:Gene Products, rev; D019444:Vaccines, DNA; D054321:rev Gene Products, Human Immunodeficiency Virus