Envelope characteristics in individuals who developed neutralizing antibodies targeting different epitopes in HIV-1 subtype C infection.

Envelope characteristics in individuals who developed neutralizing antibodies targeting different epitopes in HIV-1 subtype C infection.
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DOI:
10.1016/j.virol.2020.03.003
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发表时间:
2020-07
期刊:
影响因子:
3.7
通讯作者:
Ndung'u T
Ndung'u T
中科院分区:
医学3区
文献类型:
--
作者:
Ndlovu B;Gounder K;Muema D;Raju N;Hermanus T;Mthethwa Q;Robertson K;Walker BD;Georgiev IS;Morris L;Moore PL;Ndung'u T

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广泛中和抗体(bNAb)可能构成HIV-1保护性疫苗的重要组成部分,但没有免疫原能够引发它们。为了表征HIV-1 C亚型感染个体中bNAb的发展,使用一组18种Env假型病毒筛选18名研究参与者。针对Env突变体和MPER嵌合体绘制血浆中和的特异性。通过单基因组扩增和测序来表征包膜(env)基因序列进化。18个个体中有3个产生了广泛的血浆中和活性(>60%宽度)。三个参与者中的两个可以分别靶向包括在CD 4结合位点中的D环的位置276处的聚糖和332聚糖超位点处的聚糖的表位。这些聚糖的缺失与中和抗性相关。我们的研究描述了血浆中和活性的发展动力学,并确定了氨基酸残基的变化,提示对假定表位的免疫压力。这项研究增强了我们对HIV-1亚型C感染过程中中和宽度如何发展的理解。
Broadly neutralizing antibodies (bNAbs) may constitute an essential component of a protective vaccine against HIV-1, yet no immunogen has been able to elicit them. To characterize the development of bNAbs in HIV-1 subtype C infected individuals, a panel of 18 Env-pseudotyped viruses was used to screen 18 study participants. The specificity of plasma neutralization was mapped against Env mutants and MPER chimeras. Envelope (env) gene sequence evolution was characterized by single genome amplification and sequencing. Three out of eighteen individuals developed broad plasma neutralizing activity (>60% breadth). Two of the three participants may target epitopes comprising glycans at position 276 of the D loop in the CD4 binding site and 332 glycan supersite, respectively. Deletion of these glycans was associated with neutralization resistance. Our study describes the kinetics of the development of plasma neutralizing activity and identified amino acid residue changes suggestive of immune pressure on putative epitopes. The study enhances our understanding of how neutralization breadth develops in the course of HIV-1 subtype C infection.
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