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Cross-neutralizing activity of human anti-V3 monoclonal antibodies derived from non-B clade HIV-1 infected individuals

机译:源自非B进化枝HIV-1感染者的人类抗V3单克隆抗体的交叉中和活性

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摘要

One approach to the development of an HIV vaccine is to design a protein template which can present gp120 epitopes inducing cross-neutralizing antibodies. To select a V3 sequence for immunogen design, we compared the neutralizing activities of 18 anti-V3 monoclonal antibodies (mAbs) derived from Cameroonian and Indian individuals infected with clade AG and C, respectively. It was found that V3 mAbs from the Cameroonian patients were significantly more cross-neutralizing than those from India. Interestingly, superior neutralizing activity of Cameroonian mAbs was also observed among the nine VH5-51/VL lambda genes encoding V3 mAbs which mediate a similar mode of recognition. This correlated with higher relative binding affinity to a variety of gp120s and increased mutation rates in V3 mAbs from Cameroon. These results suggest that clade C V3 is probably weakly immunogenic and that the V3 sequence of CRF02_AG viruses can serve as a plausible template for vaccine immunogen design.
机译:开发HIV疫苗的一种方法是设计一种蛋白质模板,该模板可以呈现可诱导交叉中和抗体的gp120表位。为了选择用于免疫原设计的V3序列,我们比较了分别来自感染了进化枝AG和C的喀麦隆和印度个体的18种抗V3单克隆抗体(mAb)的中和活性。发现来自喀麦隆患者的V3单克隆抗体比来自印度的V3单克隆抗体具有更大的交叉中和作用。有趣的是,在介导相似识别方式的编码V3 mAb的9个VH5-51 / VL lambda基因中,也观察到了喀麦隆mAb的优异中和活性。这与对各种gp120的较高相对结合亲和力和来自喀麦隆的V3 mAb的突变率增加相关。这些结果表明进化枝C V3可能是弱免疫原性的,并且CRF02_AG病毒的V3序列可以用作疫苗免疫原设计的合理模板。

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