Anti-HIV env immunities elicited by nucleic acid vaccines.
Plasmid DNA vaccines encoding HIV-1 env were used to immunize mice and nonhuman primates. Plasmids were prepared that produced either secreted gp120 or full-length gp160. Mice immunized with gp120 DNA developed strong antigen-specific antibody responses, CD8+ cytotoxic T lymphocytes (CTL) (following in vitro restimulation with gp120-derived peptide), and showed in vitro proliferation and Th1-like cytokine secretion [gamma-interferon, interleukin (IL)-2 with little or no IL-4] by lymphocytes obtained from all lymphatic compartments tested (spleen, blood, and inguinal, iliac, and mesenteric lymph nodes). This indicated that systemic anti-gp120 cell-mediated immunity was induced by this DNA vaccine. Although similar antibody responses were observed in mice immunized by either intramuscular or intradermal routes, T cell responses were significantly stronger in mice injected intramuscularly. Rhesus monkeys immunized with both gp120 and gp160 DNAs exhibited significant CD8+ CTL responses, following in vitro restimulation of peripheral blood lymphocytes with antigen. These experiments demonstrate that DNA immunization elicits potent immune responses against HIV env in both a rodent and a nonhuman primate species.
Shiver
J W
JW
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.
Davies
M E
ME
Yasutomi
Y
Y
Perry
H C
HC
Freed
D C
DC
Letvin
N L
NL
Liu
M A
MA
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D004279:DNA, Viral / Q000276:immunology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics*; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D004279:DNA, Viral; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C082068:HIV-1 IIIB gp120 subunit vaccine; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic