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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 无法诱导保护性的体液反应，朝着HIV-1疫苗迈进的进展受到阻碍。特征良好的中和表位对大多数患者分离株上的免疫原性或有效掩盖。较新的证据表明，即使是高度掩盖的原发性分离株也具有敏感的中和靶标，这些靶标被自体患者血清识别，偶尔通过异源血清识别。这表明映射所涉及的表位可以确定能够诱导广泛中和活动的新目标。 在这个项目中，我们正在识别具有广泛中和活性的主要分离株活性的亚型B和C的亚型，并将定位目标表位。我们在介导自体和异源进化枝B和进化枝C病毒包膜（ENV）糖蛋白的抗体活性中很有趣。正在筛选从北美和非洲人群获得的大量患者样品进行跨中和活动，并选择具有有趣的中和特性的样品以详细表征。预计这些研究将定义出在典型的耐耐中和原代分离株上暴露的新靶标。 迄今为止，我们已经从赞比亚人群中筛选了50多个血浆样品，从赞比亚人群感染的受试者进行了一组跨层参考参考小组，以量化交叉中和非中和活性的效率和广度。亚型感染的患者总体产生的抗体可以中和效力低下的异源环境，尽管这些抗体的靶标和性质尚不清楚。我们已经确定了一个对异源环境具有广泛和有效的中和活性的受试者，并且正在表征该患者中自体病毒ENV和抗体中和活性的过程，并产生单克隆抗体。