. The focus of the proposed research is to target HIV-1 gene products to major histocompatibility class II (MHC II) pathways for antigen processing and presentation. Towards this goal, the investigator has developed a novel series of gene constructs encoding chimeric HIV antigens fused to the targeting sequence of lysosomal membrane glycoproteins (LAMP). In preliminary studies, the investigator has shown that HIV envelope protein fused with the LAMP cytoplasmic tail sequence exhibited an enhanced immune response which is attributed to increase in the MHC II peptide concentration presented to CD4+ T cells by antigen presenting cells. The investigator proposes three specific aims:
Specific Aim 1 : The application of LAMP-targeting of HIV-1 env, gag, pol and nef antigens to MHC II pathway so as to increase the CD4+ helper T cell response with a consequent increase in the immune response to these antigens.
Specific Aim 2 : An emphasis on the CTL response of cytoplasmic/nuclear proteins as a means to promote cytolytic response against conserved viral proteins in HIV-1 infected cells.
Specific Aim 3 : To apply procedures developed at the investigator's institution for conjunction of LAMP targeting DNAs to promote transfection of antigen presenting cells when the plasmid DNA is injected intramuscularly. The investigator points out that the SIV-LAMP chimeras will be constructed using a recombinant vaccinia vector suitable for immunization of non-human primates and made available for analysis of protective immunization in the SIV models.
| Truong-Le, V L; August, J T; Leong, K W (1998) Controlled gene delivery by DNA-gelatin nanospheres. Hum Gene Ther 9:1709-17 |
