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首页> 外文期刊>AIDS Research and Human Retroviruses >Analysis of SIVmac Envelope-Specific Antibodies Selected Through Phage Display
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Analysis of SIVmac Envelope-Specific Antibodies Selected Through Phage Display

机译：通过噬菌体展示选择的SIVMAC包膜特异性抗体分析

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We have constructed a single chain fragment variable (scFv) phage display library from a simian immunodeficiency virus (SIV)-infected rhesus macaque that developed unusually high-titer neutralizing antibody responses against tier-3, neutralization-resistant SIVmac239. The library was screened using trimeric (gp140) and monomeric (gp120) forms of the SIVmac239 envelope (Env) glycoprotein. We also cloned variable-heavy and variable-light (VH-VL) antibody fragments from seven previously described rhesus macaque B-cell lines (BLCLs) that produce SIV gp120-specific monoclonal antibodies (mAbs). Thirty-two gp140-specific mAbs were selected along with 20 gp120-specific ones. gp120-specific mAbs were only from the VH4 family, while gp41-specific mAbs were primarily from VH1, followed by VH4 and VH3. Rhesus macaque BLCL-derived mAbs belonged primarily to the VH4 family of antibodies followed by VH3 and a smaller number of VH1s. A preferential VH combination with Vλ light chain was observed with phage display-selected SIV Env-specific mAbs (gp120 and gp140), but not with BLCL-derived antibodies or the unpanned library. None of the tested antibodies had detectable neutralizing activity against tier-3 SIVmac239. The majority of gp120-specifc mAbs potently neutralized tier-1 SIVmac316 with 50% inhibitory concentration (IC50) values below 1?μg/ml. For gp140-specific antibodies, which were all specific for the gp41-subunit, 2 out of 11 tested neutralized SIVmac316 (IC50 of 7 and 5?μg/ml, respectively). These data suggest an order of preferential VH segment usage for SIV-specific antibodies in rhesus macaques. These antibodies will be useful in assessing the contribution of non-neutralizing antibodies to inhibition of SIV infection in vitro and in vivo .
机译：我们已经构建了一种来自Simian免疫缺陷病毒（SIV）的单链片段变量（SCFV）噬菌体展示库（SIV） - 摄入的恒星，其显影出对Tier-3的中和中和抗体反应的异常高滴度的抗体反应。使用三聚体（GP140）和SiVMac239封套（ENV）糖蛋白的单体（GP120）形式进行筛选文库。我们还克隆了来自七个先前描述的恒河猴B细胞系（Blcls）的可变重和可变光（VH-VL）抗体片段，其产生SIV GP120特异性单克隆抗体（MAb）。选择三十二个GP140特异性mAb，以及20gP120特异性的MAb。 GP120特异性mAb仅来自VH4家族，而GP41特异性mAb主要来自VH1，其次是VH4和VH3。恒河猴的Blcl衍生的mAb主要属于VH4抗体，其次是VH3和较少的VH1。用噬菌体显示选择的SIV特异性mAb（GP120和GP140）观察到与Vλ轻链的优先VH组合，但不具有Blcl衍生的抗体或未阻碍的文库。没有测试的抗体对Tier-3 SiVMac239具有可检测的中和活性。大多数GP120-ICITIMC MAbs有效地中和Tier-1 SiVMac316，具有50％抑制浓度（IC50）值低于1〜μg/ ml。对于GP140特异性抗体，其全部对GP41-亚基特异性，其中11个测试中和的SiVMac316中的2个（分别为7和5≤μg/ ml）。这些数据表明恒河猴中SIV特异性抗体的优先VH段使用顺序。这些抗体可用于评估非中和抗体在体外和体内抑制SIV感染的贡献。

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