Traditionally, immune therapeutic vaccination against viruses has utilized either live attenuated preparations, whole killed virus or recombinant proteins. Of these approaches, only live attenuated virus preparations activate all arms of the immune system in a manner similar to infection. Genetic immunization is dependent upon injection of a nucleic acid sequence directly into a host target tissue. In theory, direct genetic immunization should mimic aspects of attenuated vaccines in that synthesis of specific foreign proteins would be accomplished in the host and become the subject of immune surveillance via both the MHC class I and class II pathways. The use of this new technology to immunize animals with human immunodeficiency virus type 1 (HIV-1) envelope gp 160 DNA constructs and achieve relevant immune responses has been reported by this group. Antisera from genetically immunized animals including, mice, rabbits and non-human primates, contains anti-HIV envelope glycoprotein immune responses. The antiserum neutralizes HIV 1 infection and inhibits cell to cell infection in vitro. This technology induced both T cell proliferation and isotype switching consistent with the production of relevant T helper immune responses. Heterologous lysis of relevant env expressing targets was induced by immune spleenocytes from mice and primates. This in vivo anti HIV-1 data support the utility of this technology for anti- HIV immune therapeutic strategies. The chimpanzee is the prototypic model for HIV infection studies. The goal of this project is to evaluate the safety and efficacy of genetic inoculation with human immunodeficiency virus (HIV) constructs encoding gap/pol or env given singly or in combination in chimpanzees infected with HIV-1. Additionally, the analysis of viral load and immune responses in infected animals following genetic inoculation will generate important data regarding the immunogenicity and utility of this approach as a therapeutic strategy for HIV-1 infection. Additionally, this project will focus on the detailed analysis of humoral and cellular immune responses of the patients participating in project 3 and for the SIV studies in project 1.
