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 secret ed gp120 or full-length gp160. Mice immunized with gp120 DNA developed strong antigen-specific antibody responses, CD8+ cytotoxic T lymphocy tes (CTL) (following in vitro restimulation with gp120-derived peptide ), and showed in vitro proliferation and Thl-like cytokine secretion [ gamma-interferon, interleukin (IL)-2 with little or no IL-4] by lympho cytes obtained from all lymphatic compartments tested (spleen, blood a nd inguinal, iliac, and mesenteric lymph nodes). This indicated that s ystemic anti-gp120 cell-mediated immunity was induced by this DNA vacc ine. Although similar antibody responses were observed in mice immuniz ed by either intramuscular or intradermal routes, T cell responses wer e significantly stronger in mice injected intramuscularly. Rhesus monk eys 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 immun ization elicits potent immune responses against HIV env in both a rode nt and a nonhuman primate species. (C) 1997 Elsevier Science Ltd.