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

描述（由申请人提供）：我们提出了非常规的，独特的和非常新颖的方法来揭示gp120可变环中广泛中和的表位结构。这项工作挑战了标准范式，即gp120的可变环过于动态和可变，无法在疫苗中具有有用的保守表位。我们能够设计一种新的计算去噪方法来处理这些环中的序列和结构变异性，并且很有可能鉴定出针对V1， V2， V4和/或V5表位的第一个广泛中和抗体。基于V3循环的初步结果，我们有信心取得这一重大成果。该研究小组和拟议的研究是唯一适合于HIT-IT计划的既定目标的，而不是传统的研究资助（R01）申请。这是因为我们在这种针对V3循环的创新方面有良好的记录，而且因为这项研究解决了一个对艾滋病毒疫苗至关重要的问题，同时也被认为是目前难以解决的问题。

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.