Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex
Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex
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DOI：
10.1073/pnas.1415789111
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发表时间：
2014-12-09
影响因子：
11.1
通讯作者：
Burton, Dennis R.
中科院分区：
文献类型：
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作者：
Sok, Devin;van Gils, Marit J.;Burton, Dennis R.
针对HIV包膜三聚体顶点的广泛中和抗体（bnAbs）由于其巨大的中和广度和效力而成为疫苗设计和免疫治疗的首选候选物。然而，针对该位点分离bnab的方法受到表位区域的第四纪性质的限制。在这里，我们报道了使用重组HIV包膜三聚体BG505 SOSIP.664 gp140作为亲和试剂，从慢性感染供者的外周血单个核细胞中分离出四元依赖性bnAbs。新分离的bnAbs被命名为“PGDM1400-1412”，显示出广泛的中和广度和效力。其中一种变体PGDM1400异常广泛和有效，其跨枝中和覆盖率为83%，中位IC50为0.003 μ g/mL。总的来说，我们的结果突出了BG505 SOSIP的实用性。664 gp140作为分离四元依赖性抗体的工具，揭示了克隆家族中针对三聚体顶点的抗体反应的马赛克。
Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 mu g/mL. Overall, our results highlight the utility of BG505 SOSIP. 664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.