HIV-1 gp120-Conjugate Vaccines

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DESCRIPTION (provided by applicant): HIV-1 envelope subunit vaccines generally fail to induce broadly cross-neutralizing antibodies against primary HIV-1 isolates. One possible reason is that carbohydrates covering the surface of gp120 may block efficient immune recognition/processing, thereby limiting immune recognition of neutralization epitopes. This proposal describes strategies to convert gp120 into a more immunogenic molecule capable of eliciting antibodies that neutralize a diversity of HIV-1 primary isolates. This proposal has one specific aim which is to test the hypothesis that a model vaccine consisting of gp120-cyanovirin complexes will elicit antibodies that neutralize a diversity of primary HIV-1 isolates in contrast to uncomplexed gp120, which does not induce such neutralizing antibody responses. Cyanovirin binds with high affinity and specificity to high mannose oligosaccharide moieties on HIV-1 gp120. We will immunize guinea pigs with gp120-CVN complexes and assess hurmoral immune responses. It is proposed that CVN complexed to gp120 will function as a carrier protein to change the immunogenicity of gp120 in several possible ways. Coating the sugars with a small protein may improve transport and processing. Secondly, the carrier protein may enhance immunity to gp120 by activating carrier-specific T cells will provide help in eliciting responses to less immunogenic epitopes of gp120. A third consideration is that immune recognition of the CD4 binding site on gp120 may be dampened by the binding of gp120 to CD4 positive cells in vivo. Cyanovirin is known to block binding of soluble gp120 to cellular CD4 and this property may allow more efficient presentation this potentially important group of epitopes. We will also explore the possibility that gp120-CVN complexes will induce antibodies similar to the HMAb2G12 which recognizes a glycan-dependent epitope that is weakly immunogenic in HIV infected patients.