Gp160, the major surface protein on HIV, is composed of 2 key subunits, gp120 and gp41. Within either subunit there can be found regions of interest for vaccine development efforts; both gp120 and gp41 contain zones or sub domains that play fundamental biochemical roles in the infection process. There also are key points of contact for targeting highly conserved regions of gp120 and gp41 with vaccine-inducing antibodies. These areas will remain well preserved despite most of the virus undergoing rapid mutational changes. So, a major goal of HIV vaccine design is to develop a vaccine that elicits antibodies that recognize the highly conserved and functional parts of gp160. At least 2 highly conserved functional regions can be found in the HIV envelope protein, gp160. 1 is the C4 domain found in gp120. The C4 domain is considered to be an integral component of gp120 that mediates the ability of the viral envelope to bind to cells in the first step of the HIV infection process. Without 1 specific amino acid in the C4 domain, HIV will not infect cells. A second highly conserved functional part of gp160 is the area in gp41 that is the epitope for 4E10, a broadly effective monoclonal antibody that blocks most strains and clades of HIV from infecting susceptible cells. The epitope for 4E10 is believed to play a major role in the fusion process that completes the infection process by literally fusing the recipient cell membrane with the HIV surface membrane. Both regions are unique in-so-far-as they are very highly conserved among all strains and clades of HIV. As such, an immunogen composed of a cocktail that elicits anti C4 domain and 4E10-like antibody responses in humans would be a huge advance toward the goal of designing a safe and effective vaccine against HIV. For over a decade, we have been developing methods in peptide chemistry to induce linear synthetic peptides to assume new conformations. For this study, we will focus exclusively on testing a cocktail of 2 new conformationally conserved biomaterials from the C4 domain of gp120 and the 4E10 epitope from gp41 as a potential vaccine against HIV. In rabbits, the 2 materials have been found to independently elicit antibodies that react with gp160 and they will be tested together for optimal immune responses. The commercial opportunities for a successful immunogen that acts to block HIV infection are enormous. ? This project is geared toward creating vaccine components for HIV that will resist the tendency of HIV to mutate and elude normal immune responses. Such novel vaccine components should be useful to combat HIV infection throughout all of the world. ? ? ?
