Autologous HIV antibodies for viral control

用于病毒控制的自体 HIV 抗体

• 批准号: 10438931
• 负责人: Jonathan Li
• 金额: $ 22.23万
• 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/10438931
• 关键词: AIDS clinical trial group; Address; Aftercare; Antibody Formation; Antibody Response; Antiviral Response; Autologous; Automobile Driving; B-Lymphocytes; Chronic; Development; Disease remission; Early treatment; Goals; HIV; HIV Antibodies; HIV Infections; Immune response; Individual; Infection; Interruption; Knowledge; Lead; Mediating; Neutralizing antibody assay; 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

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.

项目摘要 拟议研究的主要目标是确定自体中和抗体在 在治疗中断后选择反弹的艾滋病毒变体并导致艾滋病毒后治疗 控制。尽管大多数艾滋病毒感染者会在艺术后经历快速病毒反弹 中断，有罕见的人，称为治疗后控制器（PTC），他们证明了持续的 停止治疗后数月或数年的病毒学抑制。我们对艾滋病毒冠军研究的分析 PTC已显示出感染后早期开始ART的个体的治疗后控制增加。 但是，该领域的关键知识差距包括我们对哪些病毒变异的不完全理解 在治疗中断后（即“可恢复的储层”）和后背后的机制后，艾滋病毒反弹 治疗控制，包括早期艺术计划如何降低艾滋病毒缓解障碍。中和抗体 代表针对广泛病毒的关键适应性免疫响应。而抗HIV抗体发生 在未治疗的急性感染期间，免疫反应的成熟需要时间，因为它可能需要几个 在针对HIV的潜在自体中和抗体（ANAB）之前的几个月。然而， 在没有艺术的情况下，连续的病毒复制可以快速病毒逃生并使体液变得 反应在控制HIV感染方面基本无效。已经发现早期艺术倡议限制了规模 艾滋病毒储量的多样性，同时保留B细胞抗病毒免疫。在此提案中，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。这 拟议的研究有可能导致该领域的关键范式转移，包括抗HIV免疫 早期艺术倡议之后的反应可以成熟和发展，驱动HIV反弹的病毒种群 在艺术中​​，中断不是纯粹的随机过程，并提供了背后的第一个机械解释 早期倡议降低艾滋病毒缓解障碍的能力。