Analysis of the neutralization breadth of the anti-V3 antibody F425-B4e8 and re-assessment of its epitope fine specificity by scanning mutagenesis
Analysis of the neutralization breadth of the anti-V3 antibody F425-B4e8 and re-assessment of its epitope fine specificity by scanning mutagenesis
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DOI：
10.1016/j.virol.2007.03.007
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发表时间：
2007-08-01
期刊：
影响因子：
3.7
通讯作者：
Burton, Dennis R.
中科院分区：
文献类型：
--
作者：
Pantophlet, Ralph;Aguilar-Sino, Rowena O.;Burton, Dennis R.
HIV-1的交叉中和抗体的鉴定对于设计旨在在免疫后引发类似抗体的抗原是重要的。先前已提出单克隆抗体（mAb）F425-B4 e8结合V3碱基处的表位，并显示中和两种主要HIV分离株。在这里，我们使用40个成员的原发性HIV-1组评估了mAb F425-B4 e8的中和宽度，并确定了mAb的表位特异性。该抗体能够中和8个进化枝B病毒（n=16）、1个进化枝C病毒（n=11）和2个进化枝D病毒（n=6），因此将其置于迄今为止描述的更广泛中和的抗V3抗体中。与最初的报道相反，我们对V3区进行扫描诱变得到的309个结果表明，mAb F425-B4 e8主要与V3的冠部/尖端相互作用，特别是Ile（309）、Arg（315）和Phe（317）。尽管mAb F425- 134 e8的中和宽度有些有限，但本文提供的结果，沿着其他交叉中和抗V3 mAb的分析，可能有助于基于模板设计靶向V3的抗原，并允许中和抗体可接近V3区的HIV-1毒株。(c)2007年爱思唯尔公司All rights reserved.
The identification of cross-neutralizing antibodies to HIV-1 is important for designing antigens aimed at eliciting similar antibodies upon immunization. The monoclonal antibody (mAb) F425-B4e8 had been suggested previously to bind an epitope at the base of V3 and shown to neutralize two primary HIV isolates. Here, we have assessed the neutralization breadth of mAb F425-B4e8 using a 40-member panel of primary HIV-1 and determined the epitope specificity of the mAb. The antibody was able to neutralize 8 clade B viruses (n=16), 1 clade C virus (n=11), and 2 clade D viruses (n=6), thus placing it among the more broadly neutralizing anti-V3 antibodies described so far. Contrary to an initial report, 309 results from our scanning mutagenesis of the V3 region suggest that mAb F425-B4e8 interacts primarily with the crown/tip of V3, notably Ile(309), Arg(315), and Phe(317). Despite the somewhat limited neutralization breadth of mAb F425-134e8, the results presented here, along with analyses from other cross-neutralizing anti-V3 mAbs, may facilitate the template-based design of antigens that target V3 and permit neutralization of HIV-1 strains in which the V3 region is accessible to antibodies. (c) 2007 Elsevier Inc. All rights reserved.