Research Project
2071197
DESCRIPTION: (Adapted from the applicant's abstract) This Phase I application follows up on the collaborative efforts of Apollon and the Institute for Biotechnology and Advanced Molecular Medicine at the University of Pennsylvania. These efforts recently yielded a report describing the successful immunization of mice against the HIV-1 coat protein (gp160) using the technique of genetic vaccination. Animals were directly inoculated with DNA containing the HIV-1 gp160 gene, resulting in humoral and cellular immunity to the HIV gp160. More recent work has demonstrated protection from a normally lethal cell challenge with a murine myeloma expressing gp160. For the present application, various plasmids will be constructed, used alone or modified for inoculation, that will induce an immune response directed against either SIV or HIV-1 gene products. Plasmids will be modeled after the one used in the successful gp160 HIV experiments; however, the genes for many of the SIV and HIV proteins will be incorporated into the plasmids.Construction will be accomplished using standard recombinant DNA cloning techniques. Several of the HIV constructs or modified constructs will be designed to be safely compatible with human inoculation in anticipation of their use in human clinical trials. The immediate objectives of this Phase I study will be (i) construction of the plasmids, (ii) evaluation of the levels of protein expression in human rhabdomyosarcoma and murine myeloma cells that have been transfected with the constructs of interest, and (iii) evaluation of immunogenicity using mice and guinea pigs to provide a logical basis for the selection of plasmids for further development as components of a genetic vaccine for HIV-1 (GENEVAX-HIV). The long-term goal of this work will be the development and commercialization of GENEVAX-HIV for the possible treatment and/or prophylaxis of HIV-infected persons.
