This is a Phase I proposal based on the potential protective immunogencity of DP-178 a 36mer peptide derived from the conserved alpha helical membrane-proximal domain of the HIV gp41 TM. This gp41 region is of interest because it is involved in membrane fusion and viral entry and the epitope of one neutralizing mAb, 2F5, overlaps this sequence. Based on preliminary data demonstrating HIV-neutralizing activity in sera from 2 of 3 DP-178-immunized guinea pigs, the PI proposes 3 Specific Aims: (1) to optimize the immune response to DP-178 in guinea pigs by adding terminal residues, conjugating to KLH, and employing different adjuvants; (2) to test the breadth of serum neutralization using a panel of HIV isolates; and (3) to map the epitopes responsible for neutralization. These studies are intended to serve as prelude to protective immunity experiments in macaques planned for Phase II.
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