Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth and potency.

Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth and potency.
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磨练出更有力的锤头可以提高广泛中和抗体的广度和效力。

DOI:
10.1172/jci82057
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发表时间:
2015
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Lewis,GeorgeK
Lewis,GeorgeK
中科院分区:
--
文献类型:
--
作者:
Lewis,GeorgeK

文献摘要

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虽然目前的HIV-1疗法极大地改善了感染者的生活质量和持续时间,但缺乏防止病毒传播的疫苗。已从HIV-1感染者中分离到具有中和多种HIV-1变异株能力的广谱中和单抗,由于它们有可能用于HIV-1疫苗接种,人们一直在努力研究这些bnmAb是如何产生的。在这一期的JCI中,Willis和他的同事应用计算方法来设计bnmAbPG9的变体,试图提高效力和中和广度。由于长重链互补决定区3(HCDR3)的稳定,其中一个变异体能够靶向多个耐PG9的菌株。这项研究的结果为优化HIV-1 bnmAbs提供了重要的洞察力和独特的方法。
While current HIV-1 therapies have greatly improved the quality and duration of life for infected individuals, a vaccine to prevent transmission of the virus is lacking. Broadly neutralizing monoclonal antibodies (bnmAbs) with the capacity to neutralize multiple HIV-1 variants have been isolated from HIV-1–infected individuals, and there has been a great effort to investigate how these bnmAbs arise, due their potential for HIV-1 vaccination. In this issue of theJCI, Willis and colleagues apply a computational approach to design variants of the bnmAb PG9 in an attempt to enhance potency and neutralization breadth. One of these variants was able to target multiple PG9-resistant strains, as the result of stabilization of the long heavy chain complementarity determining region 3 (HCDR3). The results of this study provide important insight and a unique approach to optimizing HIV-1 bnmABs.