V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1.
V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1.
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V1/V2中和表位在HIV-1的不同非M组中保守。
DOI：
10.1097/qai.0000000000000854
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Barin F
中科院分区：
文献类型：
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作者：
Morgand M;Bouvin-Pley M;Plantier JC;Moreau A;Alessandri E;Simon F;Pace CS;Pancera M;Ho DD;Poignard P;Bjorkman PJ;Mouquet H;Nussenzweig MC;Kwong PD;Baty D;Chames P;Braibant M;Barin F
补充数字内容可在正文中找到。从感染HIV-1 M组变种的个体中获得了高度有效的广中和单抗(BNAbs)。我们分析了这些bNAbs对Non-M初级分离株(PI)的跨群中和效力。用TZM-bl细胞进行中和试验，分析其对中和的敏感性。使用了23个bNAb，包括针对CD4结合位点、N160糖链-V1/V2位点、N332糖链-V3位点、gp41膜近端外区的试剂，以及跨越两个env亚基的复合表位。这项研究包括两种双特异性抗体(PG9-iMab和PG16-iMab)，它们结合了抗CD4抗体和PG9或PG16 bNAbs的抑制活性。只有靶向N160多糖-V1/V2位点的bNAbs才能观察到跨基团的中和作用。4个O组PI、1个N组PI和P组PI分别被低浓度(0.04~9.39μg/mL)的PG9和/或PG16或PGT145中和。除10E8弱中和2个N组PI和35O22弱中和1个O组PI外，其余非M组PI均未被最高浓度的针对其他区域的bNAbs所中和。除2株O群菌株外，双特异性bNAb对所有非MPI均有很好的中和作用，IC_(50)均在1μg/mL以下。N160-Glycan-V1/V2位点是4组HIV-1病毒中最保守的中和位点。这使得它成为开发艾滋病毒疫苗免疫原的一个有趣的目标。相应的bNAbs可用于非M变异体感染患者的免疫治疗策略。
Supplemental Digital Content is Available in the Text. Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI). The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs were included in the study (PG9-iMab and PG16-iMab). Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04–9.39 μg/mL). None of the non-M PIs was neutralized by the bNAbs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22 that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently all the non-M PIs with IC50 below 1 μg/mL, except 2 group O strains. The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4 groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic strategies in patients infected by non-M variants.