Use of broadly neutralizing antibodies for HIV-1 prevention.
Use of broadly neutralizing antibodies for HIV-1 prevention.
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DOI：
10.1111/imr.12511
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发表时间：
2017-01
影响因子：
8.7
通讯作者：
Haigwood NL
中科院分区：
文献类型：
--
作者：
Pegu A;Hessell AJ;Mascola JR;Haigwood NL
抗体在抗病毒治疗中有着悠久的历史，但直到最近，由于早期人类单克隆抗体（MAb）的效力和广度有限，以及难以克服的技术，财务和后勤障碍，它们还没有被积极地用于HIV-1。最近在鉴定和表征具有有效中和多种HIV-1分离株能力的单克隆抗体方面的进展重新激发了对这些产品在人体中的讨论和测试，因为新的广泛中和单克隆抗体（bnMAbs）更有可能有效对抗全球HIV-1菌株。在动物模型中，有大量证据表明bnMAb可以以剂量依赖性方式阻断感染，并且更有效的bnMAb将允许在实际可实现的输注剂量下进行临床测试。此外，抗体工程的最新进展正在提供MAb效力、宽度和半衰期的进一步改进。本文综述了bnMAb在动物模型中的保护领域的现状，以及对抗病毒活性至关重要的变量的审查。目前有几种bnMAb正在进行临床测试，我们提供了关于它们作为暴露前预防（PrEP）的观点，除了杀菌免疫之外的潜在益处，以及对未来设计新分子方法的讨论。
Antibodies have a long history in antiviral therapy, but until recently they have not been actively pursued for HIV-1 due to modest potency and breadth of early human monoclonal antibodies (MAbs) and perceived insurmountable technical, financial, and logistical hurdles. Recent advances in the identification and characterization of MAbs with the ability to potently neutralize diverse HIV-1 isolates has reinvigorated discussion and testing of these products in humans, since new broadly neutralizing MAbs (bnMAbs) are more likely to be effective against worldwide strains of HIV-1. In animal models, there is abundant evidence that bnMAbs can block infection in a dose dependent manner, and the more potent bnMAbs will allow clinical testing at infusion doses that are practically achievable. Moreover, recent advances in antibody engineering are providing further improvements in MAb potency, breadth and half-life. This review summarizes the current state of the field of bnMAb protection in animal models as well as a review of variables that are critical for antiviral activity. Several bnMAbs are currently in clinical testing, and we offer perspectives on their use as pre-exposure prophylaxis (PrEP), potential benefits beyond sterilizing immunity, and a discussion of future approaches to engineer novel molecules.