INDUCTION OF HUMORAL AND CELLULAR IMMUNE-RESPONSES TO THE HUMAN IMMUNODEFICIENCY TYPE-1 VIRUS IN NONHUMAN-PRIMATES BY IN-VIVO DNA INOCULATION

DNA inoculation has the potential to produce antigens in a native as well as a host-''customized'' form for presentation to the immune system. As such this technology may have relevance for vaccine/immune therapeutic strategies for a variety of infectious pathogens. In rodents in vivo inoculation of plasmid expression vectors encoding HIV-1 gene products leads to production of HIV-1 antigens in vivo, resulting in the production of both cellular and humoral immune responses. In primates only preliminary studies of serology have been reported. Here we report further evaluation of this new technology as a method to induce humoral and particularly cellular immune responses against a human pathogen, the HIV-1 virus, in nonhuman primates. Following inoculation and boosting of animals with an HIV gp160 plasmid expression vector we observed the induction of neutralizing responses against two diverse HIV-1 isolates in 2 of 3 vaccinated animals. T cell proliferative responses to HIV antigens were also observed in all plasmid-inoculated animals and specific cross-reactive cytotoxic T lymphocyte responses were developed in vaccinated animals. This report establishes the ability of DNA inoculation to induce cellular immune responses in nonhuman primates and suggests that further investigation of this technology with regard to human vaccine or immune therapeutic development is therefore warranted. (C) 1995 Academic Press, Inc.