NOVEL EPITOPES THAT MEDIATE BROAD NEUTRALIZATION OF CLADE B AND C HIV-1 ISOLATES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 由于无法诱导保护性体液反应，HIV-1疫苗的进展受到阻碍。特征良好的中和表位要么免疫原性差，要么在大多数患者分离株上被有效掩蔽。新的证据表明，即使是高度掩蔽的初级分离株也具有敏感的中和靶点，这些靶点可以被自体患者血清识别，有时也可以被异源血清识别。这表明，绘制相关表位图可能会识别能够诱导广泛中和活性的新靶点。在这个项目中，我们正在鉴定对初级分离株具有广泛中和活性的B和C亚型感染者，并定位目标表位。 我们感兴趣的是抗体活性，它能有效中和来自不同亚型的异源病毒包膜(Env)糖蛋白。我们从C亚型HIV-1的100多个血浆样本中筛选出对异源环境的交叉中和活性，以发现暴露在典型的抗中和初级分离株上的新靶点。在过去的资助期间，我们发现了一名C亚型感染者，其血浆具有非凡的广度和效力。我们正在鉴定这位患者的自体病毒环境和抗体中和活性，以及从B细胞产生单抗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Progress towards an HIV-1 vaccine has been stymied by the inability to induce a protective humoral response. Well-characterized neutralization epitopes are either poorly immunogenic or effectively masked on the majority of patient isolates. Newer evidence suggests that even highly masked primary isolates possess sensitive neutralization targets that are recognized by autologous patient sera and occasionally by heterologous sera. This suggests that mapping the epitopes involved may identify novel targets that are capable of inducing broadly neutralizing activities. In this project, we are identifying subtype B and C infected patients that possess broadly neutralizing activities for primary isolates, and localize the target epitopes. We are interested in antibody activities that mediate potent neutralization of heterologous viral envelope (Env) glycoproteins from various subtypes. We screened more than 100 plasma samples from subtype C HIV-1 for cross-neutralizing activities against heterologous Envs in order to discover novel targets that are exposed on typical neutralization-resistant primary isolates. In the past funding period, we identified a subtype C infected subject whose plasma possesses exceptional breadth and potency. We are in the process of characterizing the autologous viral Env and antibody neutralizing activity in this patient, as well as generating monoclonal antibodies from B cells.