HUMORAL AND CELLULAR IMMUNITIES ELICITED BY HIV-1 DNA VACCINATION

Recently it has been shown that immunization with plasmid DNA encoding genes for viral or bacterial antigens can elicit both humoral and cel lular immune responses in rodents and nonhuman primates. In this study , mice and nonhuman primates were vaccinated by intramuscular injectio n with plasmids that express either a secreted form of HIV-1 gp120 or rev proteins. Mice receiving the tPA-gp120 DNA developed antigen-speci fic antibody responses against recombinant gp120 protein and the V3 pe ptide neutralization epitope as determined by ELISA. Vaccinated mice a lso exhibited gp120-specific T cell responses, such as in vitro prolif eration of splenocytes and MHC Class I-restricted cytotoxic T lymphocy te (CTL) activities, following antigen restimulation. In addition, sup ernatants from these lymphocyte cultures showed high levels of gamma-i nterferon production compared with IL-4, suggesting that primarily typ e 1-like helper T (Th1) lymphocyte responses were induced by both vacc ines. Th1-like responses were also obtained for mice vaccinated with r ev DNA. Immune responses induced by gp120 or rev vaccines were dose-de pendent, boostable, and long-lived (greater than or equal to 6 months) . Nonhuman primates vaccinated with tPA-gp120 DNA also showed antigen- specific T lymphocyte proliferative and humoral responses, including m oderate levels of neutralizing sera against homologous HIV. These resu lts suggest that plasmid DNA may provide a powerful means for elicitin g humoral and cellular immune responses against HIV.