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Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope

The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. W...

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Autores principales: Rudometov, Andrey P., Chikaev, Anton N., Rudometova, Nadezhda B., Antonets, Denis V., Lomzov, Alexander A., Kaplina, Olga N., Ilyichev, Alexander A., Karpenko, Larisa I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789618/
https://www.ncbi.nlm.nih.gov/pubmed/31390770
http://dx.doi.org/10.3390/vaccines7030083
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author Rudometov, Andrey P.
Chikaev, Anton N.
Rudometova, Nadezhda B.
Antonets, Denis V.
Lomzov, Alexander A.
Kaplina, Olga N.
Ilyichev, Alexander A.
Karpenko, Larisa I.
author_facet Rudometov, Andrey P.
Chikaev, Anton N.
Rudometova, Nadezhda B.
Antonets, Denis V.
Lomzov, Alexander A.
Kaplina, Olga N.
Ilyichev, Alexander A.
Karpenko, Larisa I.
author_sort Rudometov, Andrey P.
collection PubMed
description The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We developed a recombinant protein, referred to as nTBI, that contains epitopes recognized by broadly neutralizing HIV-1 antibodies (bNAbs) combined with Th-epitopes. This is a modified version of a previously designed artificial protein, TBI (T- and B-cell epitopes containing Immunogen), carrying four T- and five B-cell epitopes from HIV-1 Env and Gag proteins. To engineer the nTBI molecule, three B-cell epitopes of the TBI protein were replaced with the epitopes recognized by broadly neutralizing HIV-1 antibodies 10E8, 2F5, and a linear peptide mimic of VRC01 epitope. We showed that immunization of rabbits with the nTBI protein elicited antibodies that recognize HIV-1 proteins and were able to neutralize Env-pseudotyped SF162.LS HIV-1 strain (tier 1). Competition assay revealed that immunization of rabbits with nTBI induced mainly 10E8-like antibodies. Our findings support the use of nTBI protein as an immunogen with predefined favorable antigenic properties.
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spelling pubmed-67896182019-10-16 Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope Rudometov, Andrey P. Chikaev, Anton N. Rudometova, Nadezhda B. Antonets, Denis V. Lomzov, Alexander A. Kaplina, Olga N. Ilyichev, Alexander A. Karpenko, Larisa I. Vaccines (Basel) Article The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We developed a recombinant protein, referred to as nTBI, that contains epitopes recognized by broadly neutralizing HIV-1 antibodies (bNAbs) combined with Th-epitopes. This is a modified version of a previously designed artificial protein, TBI (T- and B-cell epitopes containing Immunogen), carrying four T- and five B-cell epitopes from HIV-1 Env and Gag proteins. To engineer the nTBI molecule, three B-cell epitopes of the TBI protein were replaced with the epitopes recognized by broadly neutralizing HIV-1 antibodies 10E8, 2F5, and a linear peptide mimic of VRC01 epitope. We showed that immunization of rabbits with the nTBI protein elicited antibodies that recognize HIV-1 proteins and were able to neutralize Env-pseudotyped SF162.LS HIV-1 strain (tier 1). Competition assay revealed that immunization of rabbits with nTBI induced mainly 10E8-like antibodies. Our findings support the use of nTBI protein as an immunogen with predefined favorable antigenic properties. MDPI 2019-08-06 /pmc/articles/PMC6789618/ /pubmed/31390770 http://dx.doi.org/10.3390/vaccines7030083 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rudometov, Andrey P.
Chikaev, Anton N.
Rudometova, Nadezhda B.
Antonets, Denis V.
Lomzov, Alexander A.
Kaplina, Olga N.
Ilyichev, Alexander A.
Karpenko, Larisa I.
Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
title Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
title_full Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
title_fullStr Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
title_full_unstemmed Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
title_short Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope
title_sort artificial anti-hiv-1 immunogen comprising epitopes of broadly neutralizing antibodies 2f5, 10e8, and a peptide mimic of vrc01 discontinuous epitope
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789618/
https://www.ncbi.nlm.nih.gov/pubmed/31390770
http://dx.doi.org/10.3390/vaccines7030083
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