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

介导 B 型和 C 型 HIV-1 分离株广泛中和的新表位

• 批准号: 8357473
• 负责人: Cynthia Ann Derdeyn
• 金额: $ 3.72万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357473
• 关键词: Antibodies; Autologous; B-Lymphocytes; Epitope Mapping; Epitopes; Funding; Glycoproteins; Grant; HIV-1; Masks; Mediating; Monoclonal Antibodies; National Center for Research Resources; Patients; Plasma; Primates; Principal Investigator; Process; Research; Research Infrastructure; Resistance; Resources; Sampling; Serum; Source; United States National Institutes of Health; Vaccines; Viral; cost; immunogenic; interest; neutralizing antibody; novel; response

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 HIV-1 疫苗的进展因无法诱导保护性体液反应而受到阻碍。充分表征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盖。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点，这些靶点可以被患者自体血清识别，有时也可以被异源血清识别。这表明绘制所涉及的表位可能会识别出能够诱导广泛中和活性的新靶标。在这个项目中，我们正在鉴定对初级分离株具有广泛中和活性的 B 和 C 亚型感染患者，并定位目标表位。 我们对介导有效中和来自不同亚型的异源病毒包膜 (Env) 糖蛋白的抗体活性感兴趣。我们筛选了 100 多个来自 C 亚型 HIV-1 的血浆样本，以检测针对异源 Env 的交叉中和活性，以便发现暴露于典型中和抗性初级分离株的新靶点。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。我们正在鉴定该患者的自体病毒 Env 和抗体中和活性，并从 B 细胞中产生单克隆抗体。