Polyepitope protein incorporated the HIV-1 mimotope recognized by monoclonal antibody 2G12

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• 作者：Larisa I. Karpenko^a ; Nadezhda S. Scherbakova^a ; ^b ; Anton N. Chikaev^a ; ^{chikaev@ngs.ru} ; Olga Yu. Tumanova^a ; Leonid R. Lebedev^a ; Lyudmila A. Shalamova^a ; ^b ; Olga G. Pyankova^a ; Alexander B. Ryzhikov^a ; Alexander A. Ilyichev^a ; ^b
• 关键词：Broadly neutralizing antibodies 2G12 ; Phage peptide library ; Peptide mimotope ; Polyepitope protein ; Virus neutralization HIV-1
• 刊名：Molecular Immunology
• 出版年：2012
• 期刊代码：112_01615890
• 类别：bio
• 出版时间：April, 2012
• 卷：50
• 期：4
• 页码：193-199
• 文件大小：776 K

摘要

A major goal in HIV-1 vaccine research is to develop an immunogen that can elicit broadly neutralizing antibodies that efficiently neutralize a wide range of the HIV-1 subtypes. Using biopanning procedure we have selected linear peptide VGAFGSFYRLSVLQS mimicking the structure of discontinuous binding sites of broadly neutralizing antibodies 2G12 from phage peptide library. As a protein carrier, we used the earlier designed artificial polyepitope immunogen named TBI (T- and B-cell immunogen), which comprises B-cell and T-helper epitopes from the HIV-1 Env and Gag proteins. On the base of selected peptide mimotope VGAFGSFYRLSVLQS the artificial protein TBI-2g12 was constructed and its immunogenic properties was investigated. It was shown that the TBI-2g12 as well as the original TBI induces antibodies that recognize HIV-1 proteins and TBI protein using ELISA and immunoblotting. However only anti-TBI-2g12 serum recognized the synthetic peptide mimotope VGAFGSFYRLSVLQS, whereas the antibodies against original TBI don鈥檛 recognize it.

The neutralization assay demonstrated that serum antibodies of the mice immunized with TBI-2g12 possess virus neutralizing activity. The addition of selected peptide leads to inhibition neutralizing activity of anti- TBI-2g12 serum. We conclude from these results that immunogen TBI-2g12 containing the selected peptide VGAFGSFYRLSVLQS elicits HIV-1 neutralizing antibodies during immunization. Our data suggest that this immunogen may be useful in designing effective HIV-vaccine candidates.