title: 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.
authors.affiliation: State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region, 630559 Russia.
authors.forename: Larisa I
authors.initials: LI
authors.lastname: Karpenko
authors.forename: Nadezhda S
authors.initials: NS
authors.lastname: Scherbakova
authors.forename: Anton N
authors.initials: AN
authors.lastname: Chikaev
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Tumanova
authors.forename: Leonid R
authors.initials: LR
authors.lastname: Lebedev
authors.forename: Lyudmila A
authors.initials: LA
authors.lastname: Shalamova
authors.forename: Olga G
authors.initials: OG
authors.lastname: Pyankova
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Ryzhikov
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Ilyichev
mesh_terms: D016915:AIDS Vaccines / Q000138:chemical synthesis* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D000080908:Broadly Neutralizing Antibodies; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: C529157:2G12 monoclonal antibody; D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000080908:Broadly Neutralizing Antibodies; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019151:Peptide Library; D010455:Peptides; D014614:Vaccines, Synthetic