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: 6347229
• 负责人: THOMAS J MATTHEWS
• 金额: $ 32.05万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347229
• 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.

这个项目检查了中和抗体的反应 艾滋病毒-1感染的急性/早期阶段。最终目标是确定 如果中和抗体在清除或减少病毒感染方面发挥作用 病毒载量。基于有限数量的研究，目前的证据 提示中和抗体出现得太晚，不能对这些起作用 早期流程。我们将利用特立尼达的队列来检查 这些问题更加详细。结果将与细胞细胞进行比较 建议研究的效应器机制和其他体液反应 该计划的其他部分。该项目还将与 9002在分离和制备克隆病毒分离株和嵌合体中的应用 病毒克隆。 更具体地说，我们将跟踪抗体反应的发展 它中和源自PBMC的自体病毒分离株，以及 异源的初级和原型病毒分离株。我们会集中精力 这些对病毒和血清的努力是在早期阶段获得的 感染，并在头几年继续进行分析 血清转换后。我们还将研究幽默的其他方面 包括与包膜成分结合的抗体的免疫反应 代表中和抗体和阻断抗体的目标 病毒与CD_4的结合。在那些自体中和的情况下 很明显，我们将定义血清学和/或病毒学决定因素 牵涉其中。 目前，化验的有效性仍然存在严重的问题。 用来检测初级分离物的中和作用。治理规则 实验室适应的病毒分离株的中和不适用于初级 严重影响结果解释的分离株 将在这个项目中获得。因此，我们的一个重要组成部分 研究将是发展的努力，旨在更好地了解 影响抗体中和的实验变量。这些遗嘱 解决MOST增长所需的人工激活PBMC 初级分离株和病毒制剂的基因组复杂性。