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Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens

A successful HIV vaccine in addition to induction of antibody responses should elicit effective T cell responses. Here we described possible strategies for rational design of T-cell vaccine capable to induce high levels of both CD4+ and CD8+ T- cell responses. We developed artificial HIV-1 polyepito...

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Autores principales: Reguzova, Alena, Antonets, Denis, Karpenko, Larisa, Ilyichev, Alexander, Maksyutov, Rinat, Bazhan, Sergei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364888/
https://www.ncbi.nlm.nih.gov/pubmed/25786238
http://dx.doi.org/10.1371/journal.pone.0116412
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author Reguzova, Alena
Antonets, Denis
Karpenko, Larisa
Ilyichev, Alexander
Maksyutov, Rinat
Bazhan, Sergei
author_facet Reguzova, Alena
Antonets, Denis
Karpenko, Larisa
Ilyichev, Alexander
Maksyutov, Rinat
Bazhan, Sergei
author_sort Reguzova, Alena
collection PubMed
description A successful HIV vaccine in addition to induction of antibody responses should elicit effective T cell responses. Here we described possible strategies for rational design of T-cell vaccine capable to induce high levels of both CD4+ and CD8+ T- cell responses. We developed artificial HIV-1 polyepitope T-cell immunogens based on the conserved natural CD8+ and CD4+ T cell epitopes from different HIV-1 strains and restricted by the most frequent major human leukocyte antigen (HLA) alleles. Designed immunogens contain optimized core polyepitope sequence and additional “signal” sequences which increase epitope processing and presentation to CD8+ and CD4+ T-lymphocytes: N-terminal ubiquitin, N-terminal signal peptide and C-terminal tyrosine motif of LAMP-1 protein. As a result we engineered three T cell immunogens – TCI-N, TCI-N2, and TCI-N3, with different combinations of signal sequences. All designed immunogens were able to elicit HIV-specific CD4+ and CD8+ T cell responses following immunization. Attachment of either ubiquitin or ER-signal/LAMP-1 sequences increased both CD4+ and CD8+ mediated HIV-specific T cell responses in comparison with polyepitope immunogen without any additional signal sequences. Moreover, TCI-N3 polyepitope immunogen with ubiquitin generated highest magnitude of HIV-specific CD4+ and CD8+ T cell responses in our study. Obtained data suggests that attachment of signal sequences targeting polyepitope immunogens to either MHC class I or MHC class II presentation pathways may improve immunogenicity of T-cell vaccines. These results support the strategy of the rational T cell immunogen design and contribute to the development of effective HIV-1 vaccine.
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spelling pubmed-43648882015-03-23 Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens Reguzova, Alena Antonets, Denis Karpenko, Larisa Ilyichev, Alexander Maksyutov, Rinat Bazhan, Sergei PLoS One Research Article A successful HIV vaccine in addition to induction of antibody responses should elicit effective T cell responses. Here we described possible strategies for rational design of T-cell vaccine capable to induce high levels of both CD4+ and CD8+ T- cell responses. We developed artificial HIV-1 polyepitope T-cell immunogens based on the conserved natural CD8+ and CD4+ T cell epitopes from different HIV-1 strains and restricted by the most frequent major human leukocyte antigen (HLA) alleles. Designed immunogens contain optimized core polyepitope sequence and additional “signal” sequences which increase epitope processing and presentation to CD8+ and CD4+ T-lymphocytes: N-terminal ubiquitin, N-terminal signal peptide and C-terminal tyrosine motif of LAMP-1 protein. As a result we engineered three T cell immunogens – TCI-N, TCI-N2, and TCI-N3, with different combinations of signal sequences. All designed immunogens were able to elicit HIV-specific CD4+ and CD8+ T cell responses following immunization. Attachment of either ubiquitin or ER-signal/LAMP-1 sequences increased both CD4+ and CD8+ mediated HIV-specific T cell responses in comparison with polyepitope immunogen without any additional signal sequences. Moreover, TCI-N3 polyepitope immunogen with ubiquitin generated highest magnitude of HIV-specific CD4+ and CD8+ T cell responses in our study. Obtained data suggests that attachment of signal sequences targeting polyepitope immunogens to either MHC class I or MHC class II presentation pathways may improve immunogenicity of T-cell vaccines. These results support the strategy of the rational T cell immunogen design and contribute to the development of effective HIV-1 vaccine. Public Library of Science 2015-03-18 /pmc/articles/PMC4364888/ /pubmed/25786238 http://dx.doi.org/10.1371/journal.pone.0116412 Text en © 2015 Reguzova et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Reguzova, Alena
Antonets, Denis
Karpenko, Larisa
Ilyichev, Alexander
Maksyutov, Rinat
Bazhan, Sergei
Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens
title Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens
title_full Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens
title_fullStr Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens
title_full_unstemmed Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens
title_short Design and Evaluation of Optimized Artificial HIV-1 Poly-T Cell-Epitope Immunogens
title_sort design and evaluation of optimized artificial hiv-1 poly-t cell-epitope immunogens
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364888/
https://www.ncbi.nlm.nih.gov/pubmed/25786238
http://dx.doi.org/10.1371/journal.pone.0116412
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