Autologous HIV antibodies for viral control

用于病毒控制的自体 HIV 抗体

• 批准号: 10327100
• 负责人: Jonathan Li
• 金额: $ 28.65万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10327100
• 关键词: AIDS clinical trial group; Address; Aftercare; Antibody Formation; Antibody Response; Antiviral Agents; Antiviral Response; Autologous; Automobile Driving; B-Lymphocytes; Biological Assay; Chronic; Development; Disease remission; Early treatment; Goals; HIV; HIV Antibodies; HIV Infections; Immune response; Individual; Infection; Interruption; Knowledge; Lead; Mediating; Participant; Persons; Plasma; Play; Population; Proviruses; Research; Resistance; Role; Stochastic Processes; Thailand; Therapeutic Intervention; Time; Variant; Viral; Viral Antibodies; Virus; Virus Replication; Withholding Treatment; acute infection; adaptive immune response; antiretroviral therapy; antiviral immunity; chronic infection; cohort; experience; neutralizing antibody; preservation; pressure; response; viral rebound; virology

PROJECT SUMMARY The primary goals of the proposed study are to determine the impact of autologous neutralizing antibodies in selecting the rebounding HIV variants after treatment interruption and contributing to HIV post-treatment control. Although the majority of HIV-infected persons will experience rapid viral rebound after ART interruption, there are rare individuals, termed post-treatment controllers (PTCs), who demonstrate sustained virologic suppression for months or years after treatment cessation. Our analysis of the CHAMP study of HIV PTCs has shown an increase in post-treatment control for individuals initiating ART early after infection. However, key knowledge gaps in the field include our incomplete understanding of which viral variants will lead to HIV rebound after treatment interruption (i.e., the “reboundable reservoir”) and mechanisms behind post- treatment control, including how early ART initiation lowers the barrier to HIV remission. Neutralizing antibodies represent a key adaptive immune response against a broad range of viruses. While anti-HIV antibodies arise during untreated acute infection, maturation of the immune response requires time, as it can take several months before potent autologous neutralizing antibodies (aNAbs) against HIV are developed. However, continuous viral replication in the absence of ART allows for rapid viral escape and renders the humoral response largely ineffective in controlling HIV infection. Early ART initiation has been found to restrict the size and diversity of the HIV reservoir, while preserving B-cell antiviral immunity. In this proposal, we plan to assess the role of aNAbs in selecting for rebounding viral variants and mediating post-treatment HIV control. The proposed studies have the potential to lead to key paradigm shifts in the field, including that anti-HIV immune responses can mature and evolve after early ART initiation, that the viral populations driving HIV rebound during ART interruption is not a purely stochastic process, and provide the first mechanistic explanation behind the ability of early-ART initiation to lower the barrier to HIV remission.

项目概要 拟议研究的主要目标是确定自体中和抗体对 选择治疗中断后反弹的 HIV 变异并促进治疗后的 HIV 变异 尽管大多数 HIV 感染者在 ART 后会经历病毒快速反弹。 中断期间，有极少数人被称为治疗后控制者（PTC），他们表现出持续的 治疗停止后数月或数年的病毒学抑制。我们对 HIV CHAMP 研究的分析。 PTC 已显示出感染后早期开始 ART 的个体的治疗后控制能力有所提高。 然而，该领域的关键知识差距包括我们不完全了解哪些病毒变种将导致 治疗中断后 HIV 反弹（即“可反弹储存库”）及其背后的机制 治疗控制，包括早期开始 ART 如何降低 HIV 缓解的障碍。 当抗HIV抗体出现时 在未经治疗的急性感染期间，免疫反应的成熟需要时间，因为可能需要数次 然而，在针对 HIV 的有效自体中和抗体 (aNAb) 开发出来之前的几个月。 在缺乏抗逆转录病毒治疗的情况下，病毒的持续复制可以使病毒快速逃逸，并使体液 研究发现，早期 ART 治疗在控制 HIV 感染方面基本上无效。 和 HIV 储存库的多样性，同时保留 B 细胞抗病毒免疫力。在本提案中，我们计划评估。 aNAb 在选择反弹病毒变异和介导治疗后 HIV 控制中的作用。 拟议的研究有可能导致该领域的关键范式转变，包括抗艾滋病毒免疫 早期 ART 启动后，反应可以成熟并发展，导致 HIV 病毒种群反弹 ART期间的中断不是一个纯粹的随机过程，并提供了背后的第一个机械解释 早期 ART 启动降低 HIV 缓解障碍的能力。