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

• Published in: Molecular immunology Vol. 50; no. 4; pp. 193 - 199
• Main Authors: Karpenko, Larisa I., Scherbakova, Nadezhda S., Chikaev, Anton N., Tumanova, Olga Yu, Lebedev, Leonid R., Shalamova, Lyudmila A., Pyankova, Olga G., Ryzhikov, Alexander B., Ilyichev, Alexander A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2012
• Subjects: AIDS Vaccines - chemical synthesis; AIDS Vaccines - immunology; Amino Acid Sequence; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Blotting, Western; Broadly neutralizing antibodies 2G12; Data processing; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes; Epitopes, B-Lymphocyte - chemistry; Epitopes, B-Lymphocyte - immunology; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Gag protein; HIV Antibodies - chemistry; HIV Antibodies - immunology; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Immunization; Immunoblotting; Immunogenicity; Lymphocytes B; Mice; Mice, Inbred BALB C; Mimicry; Molecular Sequence Data; Monoclonal antibodies; Peptide libraries; Peptide Library; Peptide mimotope; Peptides - chemistry; Peptides - immunology; Phage peptide library; Phages; Polyepitope protein; synthetic peptides; Vaccines; Vaccines, Synthetic - immunology; Virus neutralization HIV-1; Broadly neutralizing antibodies 2G12; Virus neutralization HIV-1; Phage peptide library; Polyepitope protein; Peptide mimotope
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2012.01.003

► Peptide recognized by broadly neutralizing antibody 2G12 was selected with biopanning. ► Peptide was inserted into the artificial polyepitope protein TBI 2g12. ► TBI-2g12 induce HIV-neutralizing antibodies. 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’t 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.