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Increased breadth of HIV-1 neutralization achieved by diverse antibody clones each with limited neutralization breadth

机译：通过各自具有有限的中和广度的各种抗体克隆实现的HIV-1中和广度的增加

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Broadly neutralizing antibodies (bNAbs) are rarely elicited by current human immunodeficiency virus type 1 (HIV-1) vaccine designs, but the presence of bNAbs in naturally infected individuals may be associated with high plasma viral loads, suggesting that the magnitude, duration, and diversity of viral exposure may contribute to the development of bNAbs. Here, we report the isolation and characterization of a panel of human monoclonal antibodies (mAbs) from two subjects who developed broadly neutralizing autologous antibody responses during HIV-1 infection. In both subjects, we identified collections of mAbs that exhibited specificity only to a few autologous envelopes (Envs), with some mAbs exhibiting specificity only to a subset of Envs within the quasispecies of a particular sample at one time point. Neutralizing antibodies (NAbs) isolated from these subjects mapped mostly to epitopes in the Env V3 loop region and the CD4 binding site. None of the individual neutralizing mAbs recovered exhibited the cumulative breadth of neutralization present in the serum of the subjects. Surprisingly, however, the activity of polyclonal mixtures comprising individual mAbs that each possessed limited neutralizing activity, could achieve increased breadth of neutralizing activity against autologous isolates. While a single broadly neutralizing antibody targeting one epitope can mediate neutralization breadth, the findings presented here suggest that a cooperative polyclonal process mediated by diverse antibodies with more limited breadth targeting multiple epitopes also can achieve neutralization breadth against HIV-1.
机译：当前的人类免疫缺陷病毒1型（HIV-1）疫苗设计很少引起广泛中和抗体（bNAbs）的感染，但是自然感染个体中bNAbs的存在可能与血浆病毒载量高有关，这表明其强度，持续时间和病毒暴露的多样性可能有助于bNAb的发展。在这里，我们报道了从两个受试者中分离并鉴定出一组人类单克隆抗体（mAb），这些受试者在HIV-1感染期间发展了广泛中和自体抗体反应。在这两个主题中，我们确定了仅对少数几个自体包膜（Envs）表现出特异性的mAb集合，而某些mAb在某个时间点仅对特定样品的准种内的Envs子集具有特异性。从这些受试者中分离出的中和抗体（NAb）主要定位到Env V3环区域和CD4结合位点的表位。回收的个体中和mAb中没有一个表现出受试者血清中存在的累积中和宽度。然而，令人惊讶地，包含各自具有有限的中和活性的单个mAb的多克隆混合物的活性可以实现针对自体分离物的中和活性的广度增加。虽然靶向一个表位的单一广泛中和抗体可以介导中和广度，但此处提出的发现表明，由针对多个表位的广度有限的多种抗体介导的合作多克隆过程也可以实现针对HIV-1的中和广度。

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