Cytotoxic T lymphocyte and helper T cell responses following HIV polynucleotide vaccination.
Expression vectors encoding either HIV-1 gp160/rev, gp120, or rev alone were used for direct vaccination of mice and nonhuman primates. Each vaccine elicited long-lived (> 7 months) helper T cell responses in mice and monkeys as measured by in vitro proliferation of splenocytes following recombinant antigen treatment. Cytokine assays of the cell supernatants showed that approximately 100-fold more gamma-interferon than IL-4 was secreted during culture indicating that these vaccines elicited TH1-like responses. CD8+ CTL activities were also observed both in mice and rhesus. The gp120 and gp160/rev vaccines elicited antigen-specific antibodies, although these responses were more variable and lower magnitude for gp160/rev, and gp120 DNA-vaccinated African green monkeys had moderate levels of neutralizing antibodies. No antibodies were found against rev (an intracellular protein) with either rev vaccine. Similar antibody titers were obtained for gp120 by either intramuscular or intradermal injection although T cell responses were generally lower by intradermal route. These results indicate that DNA vaccines may provide a powerful means to elicit cellular and humoral immune responses against HIV.
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
J W
JW
Shiver
H C
HC
Perry
M E
ME
Davies
D C
DC
Freed
M A
MA
Liu
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D002522:Chlorocebus aethiops / Q000276:immunology; D004274:DNA, Recombinant; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015694:Gene Products, rev / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004274:DNA, Recombinant; D015686:Gene Products, env; D015694:Gene Products, rev; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D054321:rev Gene Products, Human Immunodeficiency Virus