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

Abstract:

: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.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Karpenko LI,Scherbakova NS,Chikaev AN,Tumanova OY,Lebedev LR,Shalamova LA,Pyankova OG,Ryzhikov AB,Ilyichev AA

doi

10.1016/j.molimm.2012.01.003

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

193-9

issue

4

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(12)00004-1

journal_volume

50

pub_type

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