NEUTRALIZING ANTIBODY RESPONSES IN EARLY STAGES OF HIV-1 INFECTION

中和 HIV-1 感染早期阶段的抗体反应

• 批准号: 6235544
• 负责人: THOMAS J MATTHEWS
• 金额: $ 30.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235544
• 关键词: HIV envelope protein gp120; HIV envelope protein gp41; HIV infections; T lymphocyte; acute disease /disorder; antigen antibody reaction; antiviral antibody; clearance rate; clinical research; cross immunity; human immunodeficiency virus 1; human subject; humoral immunity; longitudinal human study; microorganism immunology; molecular cloning; neutralizing antibody; virus envelope; virus infection mechanism; virus load

This project examines the neutralizing antibody responses in the acute/early phases of HIV-1 infection. The ultimate goal is to determine if neutralizing antibodies play a role in virus clearance or reduction in virus load. Based on a limited number of studies, current evidence suggests neutralizing antibodies arise too late to contribute to these early processes. We will take advantage of the Trinidad cohort to examine these questions in more detail. The results will be compared to cellular effector mechanisms and other humoral reactivities proposed for study in other sections of the program. The project will also work closely with 9002 in the isolation and preparation of cloned virus isolates and chimeric virus clones. More specifically we will follow the development of antibody responses which neutralize autologous virus isolates derived from PBMCs as well as heterologous primary and prototypic virus isolates. We will concentrate these efforts on virus and sera obtained in the earliest phases of infection and also continue the analysis through the first several years post sero-conversion. We will also examine other aspects of the humoral immune response including antibody binding to envelope components that may represent targets of neutralizing antibody as well as antibodies that block binding of virus to CD4. In those cases in which autologous neutralization is apparent we will define serologic and/or virologic determinants involved. There remain serious questions about the validity of assays currently utilized to detect neutralization of primary isolates. Rules that govern neutralization of laboratory adapted virus isolates do not apply to primary isolates which seriously impacts on the interpretation of the results that will be obtained in this project. Therefore, an important component of our studies will be developmental efforts aimed at a better understanding of experimental variables that affect antibody neutralization. These will address the artificially activated PBMCs required for growth of most primary isolates and the genomic complexity of the virus preparations.

本项目研究了在人类中的中和抗体反应， HIV-1感染的急性/早期阶段。 最终目标是确定 如果中和抗体在病毒清除或减少中起作用， 病毒载量 根据有限数量的研究，目前的证据 表明中和抗体产生得太晚， 早期进程。 我们将利用特立尼达队列研究 这些问题更详细。 结果将与细胞 效应器机制和其他体液反应，建议在 节目的其他部分。 该项目还将与 9002的分离和制备克隆病毒分离株和嵌合体 病毒克隆 更具体地说，我们将跟踪抗体反应的发展， 其中和来自PBMC的自体病毒分离物以及 异源原代和原型病毒分离株。 我们将集中 这些对病毒和血清的研究是在早期阶段进行的， 感染，并在最初几年继续分析 血清转化后。 我们还将研究体液免疫的其他方面， 免疫应答包括抗体与包膜成分的结合，包膜成分可 代表中和抗体的靶标以及阻断 病毒与CD 4的结合。 在那些自体中和 很明显，我们将定义血清学和/或病毒学决定因素 涉案 目前，关于检测的有效性仍然存在严重的问题， 用于检测初级分离株的中和。 管理的规则 实验室适应性病毒分离株的中和不适用于原发性 严重影响结果解释的分离株， 将在该项目中获得。 因此，我们的重要组成部分 研究将是旨在更好地了解 影响抗体中和的实验变量。 这些将 解决大多数人生长所需的人工活化的PBMC 主要分离株和病毒制剂的基因组复杂性。