This application focuses on the development of a novel strategy for designing and delivery of peptide antigens for HIV vaccine. Specifically, it is proposed to develop new methodology for preparing and delivery of the ectodomain chemokine receptor mimetics as HIV vaccine candidate. The rationale for developing receptor mimetics as vaccine is based on the recent reports linking HIV infectivity, tropism, and AIDS progression to coreceptors which belong to the 7-transmembrane (TM), G protein-coupled receptor family and are activated by the chemokines. Reversible blockage of these coreceptors in vitro and individuals with homozygous defect in the coreceptor allele provide evidence of correlation of HIV resistance to HIV infection. It is hypothesized that vaccination with conformationally constrained peptidyl immunogens mimicking the extracellular surface ectodomain of these coreceptors may confer useful therapeutic or preventive intervention in HIV infectivity and AIDS progression. There are two major impediments in using these 7-TM coreceptors directly as immunogens for vaccination. These include their insolubility and low immunogenicity. The goals are to design and develop soluble mimetics of the extracellular domains of these 7-TM receptors as vaccination candidates, to verify and test the mimetics biochemically and structurally, and to develop a general strategy for immunization and delivery of the CC-R5 mimetics for eliciting high-titer antisera in small animals
