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Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers uncleaved Env proteins and monomeric subunits

机译:中和性和非中和性抗体与天然样可溶性HIV-1 Env三聚体未切割的Env蛋白和单体亚基的差异结合

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摘要

BackgroundThe trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically.
机译:背景技术HIV-1病毒粒子表面的三聚体包膜糖蛋白(Env)是中和抗体(NAbs)的目标。尚无候选HIV-1免疫原诱导有效,广泛活性的NAb(bNAb)。部分解释可能是先前测试的Env蛋白不足以模拟功能性天然Env复合物。 Env前体的三聚化和蛋白水解加工成gp120和gp41极大地改变了抗原性,但是可溶性裂解的三聚体太不稳定而不能用作免疫原。通过引入稳定突变(SOSIP),我们构建了从HIV-1亚型A分离株BG505衍生而来的可溶性,裂解的Env三聚体,在结构和抗原上均类似于病毒体上的天然Env尖峰。

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