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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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。充分表征的中和表位在大多数患者分离株上的免疫原性差或被有效掩盖。较新的证据表明，即使是高度掩蔽的原代分离株也具有敏感的中和靶标，这些靶标可被自体患者血清识别，偶尔也可被异源血清识别。这表明，映射所涉及的表位可以鉴定能够诱导广泛中和活性的新靶标。在这个项目中，我们正在鉴定对主要分离株具有广泛中和活性的B和C亚型感染患者，并定位靶表位。 我们感兴趣的抗体活动，介导有效中和异源病毒包膜（Env）糖蛋白从各种亚型。我们筛选了100多份来自C亚型HIV-1的血浆样本，以检测其对异源Env的交叉中和活性，从而发现暴露于典型耐中和原代分离株上的新靶标。在过去的资助期间，我们确定了一个C亚型感染的受试者，其血浆具有特殊的广度和效力。我们正在表征该患者的自体病毒Env和抗体中和活性，以及从B细胞产生单克隆抗体。

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.