Structure-Based Characterization of gp120 Non-V3 Variable Loop Epitopes

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DESCRIPTION (provided by applicant): We propose unconventional, unique and exceptionally novel methods to uncover the structure of broadly neutralizeable epitopes in the variable loops of gp120. This work challenges the standard paradigm that the variable loops of gp120 are too dynamic and variable to have conserved epitopes useful in a vaccine. We were able to devise a novel computational de-noising approach to the sequence and structural variability in these loops and have a high likelihood of identifying the first broadly neutralizing antibodies targeting epitopes in V1, V2 V4 and/or V5. We are confident of attaining this significant outcome based on our preliminary results with the V3 loop. The research group and the proposed research is uniquely suited to the stated goals of the HIT-IT initiative, rather than a conventional research grant (R01) application. This is because we have a proven track record of this kind of innovation targeting the V3 loop, and because the research addresses a problem that is both crucial to an HIV vaccine and simultaneously thought currently to be too challenging to address.