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: 8172428
• 负责人: Cynthia Ann Derdeyn
• 金额: $ 2.74万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172428
• 关键词: African American; Antibodies; Autologous; Computer Retrieval of Information on Scientific Projects Database; Epitope Mapping; Epitopes; Funding; Glycoproteins; Grant; HIV-1 vaccine; Institution; Masks; Mediating; Monoclonal Antibodies; Patients; Plasma; Process; Property; Research; Research Personnel; Resistance; Resources; Sampling; Serum; Source; United States National Institutes of Health; Viral; cohort; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 will localize the target epitopes. We are interesting in antibody activities that mediate neutralization of both autologous and heterologous clade B and clade C viral envelope (Env) glycoproteins. A large number of patient samples obtained from both North-American and African cohorts are being screened for cross-neutralizing activities, and samples with interesting neutralizing properties will be selected for detailed characterization. It is anticipated that these studies will define novel targets that are exposed on typical neutralization-resistant primary isolates. To date, we have screened over 50 plasma samples from chronically subtype C infected subjects from a Zambian cohort against a panel of cross-clade reference Envs to quantify the potency and breadth of cross-neutralizing activity. Subtype C infected patients in general produce antibodies that can neutralize heterologous Envs with low potency, although the targets and properties of these antibodies are not yet known. We have identified one subject that possesses both broad and potent neutralizing activity against heterologous Envs and are in the process of characterizing the autologous viral Env and antibody neutralizing activity in this patient, as well as generating monoclonal antibodies.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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，并将定位目标表位。我们对介导自体和异源 B 进化枝和 C 进化枝病毒包膜 (Env) 糖蛋白中和的抗体活性感兴趣。正在对从北美和非洲队列获得的大量患者样本进行交叉中和活性筛选，并将选择具有有趣的中和特性的样本进行详细表征。预计这些研究将确定暴露在典型的中和抗性初级分离株上的新靶标。 迄今为止，我们已经根据一组跨进化枝参考环境筛选了来自赞比亚队列的慢性 C 亚型感染受试者的 50 多个血浆样本，以量化交叉中和活性的效力和广度。 C亚型感染的患者通常会产生可以中和异源包膜的低效抗体，尽管这些抗体的靶标和特性尚不清楚。我们已经鉴定出一名受试者，该受试者对异源包膜蛋白具有广泛而有效的中和活性，并且正在表征该患者的自体病毒包膜蛋白和抗体中和活性，以及​​产生单克隆抗体。