Autologous HIV antibodies for viral control

项目总结 这项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变异株并促进治疗后HIV感染 控制力。虽然大多数艾滋病毒感染者在接受抗逆转录病毒治疗后将经历病毒的快速反弹 中断，有罕见的个体，被称为治疗后控制者(PTCs)，他们表现出持续的 停止治疗后几个月或几年的病毒学抑制。我们对CHAMP艾滋病毒研究的分析 PTCS显示，感染后早期开始抗逆转录病毒治疗的个体在治疗后控制方面有所增加。 然而，该领域的关键知识空白包括我们对哪些病毒变异将导致 治疗中断后HIV的反弹(即“回弹库”)及其背后的机制 治疗控制，包括早期抗逆转录病毒治疗如何降低艾滋病毒缓解的障碍。中和抗体 代表了针对广泛病毒的关键适应性免疫反应。当抗HIV抗体出现的时候 在未经治疗的急性感染期间，免疫反应的成熟需要时间，因为这可能需要几个小时 在开发出针对艾滋病毒的有效的自体中和抗体(ANAbs)之前的几个月。然而， 在没有ART的情况下，持续的病毒复制允许病毒快速逃逸，并呈现体液 应对措施在控制艾滋病毒感染方面很难奏效。早期的艺术启蒙被发现限制了大小 在保持B细胞抗病毒免疫的同时，保持艾滋病毒储存库的多样性。在这份提案中，我们计划评估 ANAbs在选择反弹病毒变异株和调节治疗后HIV控制中的作用。这个 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 在早期ART启动后，应答可以成熟和进化，推动艾滋病毒反弹的病毒群体 艺术过程中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制解释 早期抗逆转录病毒治疗的能力，以降低艾滋病毒缓解的障碍。

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.