The overall goal of this program is to examine the use of genetically modified antigen presenting cells as vaccines for both the prevention and treatment of AIDS. The primary issue that will be address is whether manipulation of the presentation of specific SIV or HIV antigens to the immune system through the engineered expression of those antigens and potential immunostimulatory gene products in different cell types might lead to more effective immune responses against SIV or HIV that other more conventional methods of vaccination. A variety of cell types with different antigen presentation properties will be transduced so as to express single or complex mixtures of viral gene products in conjunction with potential immunostimulatory gene products. The immune response to a variety of different strategies for vaccination administration will then be characterized in detail. In order to attempt to specifically model the ability of such vaccines to eradicate cellular reservoirs AIDS to mediate to either rejection of a number of will characterized murine tumors that have been engineered to express specific viral gene products, or rejection of normal CD4+ T cells expressing the viral gene products. A number of different models of immunodeficiency will be developed in order to assess the ability of specific vaccine candidates to stimulate immune responses in immunocompromised hosts. Based on the murine studies, candidate gene products and cell types will be identified, and the appropriate methods and reagents for testing cell-based vaccines in primates and man will be generated. Collaborations with other members of the NCDVG will then be established in order to compare to efficacy of the vaccines to other vaccine candidates.
| Segal, A H (1996) Anatomic predilection of the spondyloarthropathies(-)a case of the nerves? J Rheumatol 23:491-4 |
| Burns, D P; Collignon, C; Desrosiers, R C (1993) Simian immunodeficiency virus mutants resistant to serum neutralization arise during persistent infection of rhesus monkeys. J Virol 67:4104-13 |
| Burns, D P; Desrosiers, R C (1992) A caution on the use of SIV/HIV gag antigen detection systems in neutralization assays. AIDS Res Hum Retroviruses 8:1189-92 |
| Javaherian, K; Langlois, A J; Schmidt, S et al. (1992) The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89:1418-22 |
| Kim, S; Ikeuchi, K; Groopman, J et al. (1990) Factors affecting cellular tropism of human immunodeficiency virus. J Virol 64:5600-4 |
| Kim, S; Ikeuchi, K; Byrn, R et al. (1989) Lack of a negative influence on viral growth by the nef gene of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 86:9544-8 |
