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中和威胁:利用抗HIV-1的广谱中和抗体进行治疗和预防。

Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention.

作者信息

Becerra Juan C, Hitchcock Lauren, Vu Khoa, Gach Johannes S

机构信息

Department of Medicine, Division of Infectious Diseases, University of California CA, Irvine, Irvine, 92697 USA.

出版信息

Microb Cell. 2024 Jul 3;11:207-220. doi: 10.15698/mic2024.07.826. eCollection 2024.

Abstract

Broadly neutralizing antibodies (bnAbs) targeting the human immunodeficiency virus-1 (HIV-1) have played a crucial role in elucidating and characterizing neutralization-sensitive sites on the HIV-1 envelope spike and in informing vaccine development. Continual advancements in identifying more potent bnAbs, along with their capacity to trigger antibody-mediated effector functions, coupled with modifications to extend their half-life, position them as promising candidates for both HIV-1 treatment and prevention. While current pharmacological interventions have made significant progress in managing HIV-1 infection and enhancing quality of life, no definitive cure or vaccines have been developed thus far. Standard treatments involve daily oral anti-retroviral therapy, which, despite its efficacy, can lead to notable long-term side effects. Recent clinical trial data have demonstrated encouraging therapeutic and preventive potential for bnAb therapies in both HIV-1-infected individuals and those without the infection. This review provides an overview of the advancements in HIV-1-specific bnAbs and discusses the insights gathered from recent clinical trials regarding their application in treating and preventing HIV-1 infection.

摘要

靶向人类免疫缺陷病毒1型(HIV-1)的广谱中和抗体(bnAbs)在阐明和表征HIV-1包膜刺突上的中和敏感位点以及为疫苗开发提供信息方面发挥了关键作用。在鉴定更有效的bnAbs方面的持续进展,以及它们触发抗体介导的效应功能的能力,再加上延长其半衰期的修饰,使它们成为HIV-1治疗和预防的有希望的候选者。虽然目前的药物干预在管理HIV-1感染和提高生活质量方面取得了重大进展,但迄今为止尚未开发出明确的治愈方法或疫苗。标准治疗包括每日口服抗逆转录病毒疗法,尽管其有效,但可能导致明显的长期副作用。最近的临床试验数据表明,bnAb疗法在HIV-1感染者和未感染者中都具有令人鼓舞的治疗和预防潜力。本综述概述了HIV-1特异性bnAbs的进展,并讨论了从最近的临床试验中获得的关于它们在治疗和预防HIV-1感染中的应用的见解。

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