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首页> 外文期刊>Vaccine >New approach for generation of neutralizing antibody against human T-cell leukaemia virus type-I (HTLV-I) using phage clones
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New approach for generation of neutralizing antibody against human T-cell leukaemia virus type-I (HTLV-I) using phage clones

机译:使用噬菌体克隆产生抗人I型T细胞白血病病毒(HTLV-1)的中和抗体的新方法

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We have screened a phage peptide library to address whether clones binding to a monoclonal antibody (mAb) could be isolated and if the selected phage particles would be able to elicit an in vivo immune response against the original antigen. A phage peptide library, consisting of seven random amino acids inserted in the minor coat protein (pIII), was screened for specific binding to a rat mAb LAT-27, which is capable of neutralizing human T-cell leukaemia virus type-l (HTLV-1) by binding to its envelope gp46 epitope, (amino acids LPHSNL). Total 37 clones were selected from the library and one clone named 4-2-22 was tested for its immunogenicity in three rabbits. The all rabbit immune sera showed strong binding activity to a gp46 peptide carrying the neutralization sequence, stained gp46-expressing cells and neutralized HTLV-1 in vitro as determined by cell fusion inhibition assay. These results show that the selected phage clone was capable of mimicking the epitope recognized by a HTLV-l neutralizing mAb, and it can be used as an immunogen to induce protective immune response against HTLV-1. Thus, the present methodology could be one of the approaches to develop vaccines against infectious agents in a simple and inexpensive way.
机译:我们已经筛选了噬菌体肽文库,以解决是否可以分离与单克隆抗体(mAb)结合的克隆,以及所选噬菌体颗粒是否能够引发针对原始抗原的体内免疫反应。筛选了由插入次要外壳蛋白(pIII)中的七个随机氨基酸组成的噬菌体肽文库与大鼠mAb LAT-27的特异性结合,该抗体能够中和人I型T细胞白血病病毒(HTLV) -1)通过与其包膜gp46表位结合(氨基酸LPHSNL)。从该文库中选择了总共37个克隆,并测试了一个名为4-2-22的克隆在三只兔子中的免疫原性。通过细胞融合抑制试验测定,所有兔免疫血清在体外均显示出与带有中和序列的gp46肽,染色的gp46表达细胞和中和的HTLV-1的强结合活性。这些结果表明,所选择的噬菌体克隆能够模拟被HTLV-1中和mAb识别的表位,并且可以用作诱导针对HTLV-1的保护性免疫应答的免疫原。因此,本方法学可以是以简单且廉价的方式开发针对传染剂的疫苗的方法之一。

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