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Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity

Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structura...

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Autores principales: Ito, Masaki, Hayashi, Kazumi, Adachi, Eru, Minamisawa, Tamiko, Homma, Sadamu, Koido, Shigeo, Shiba, Kiyotaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208766/
https://www.ncbi.nlm.nih.gov/pubmed/25343355
http://dx.doi.org/10.1371/journal.pone.0110425
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author Ito, Masaki
Hayashi, Kazumi
Adachi, Eru
Minamisawa, Tamiko
Homma, Sadamu
Koido, Shigeo
Shiba, Kiyotaka
author_facet Ito, Masaki
Hayashi, Kazumi
Adachi, Eru
Minamisawa, Tamiko
Homma, Sadamu
Koido, Shigeo
Shiba, Kiyotaka
author_sort Ito, Masaki
collection PubMed
description Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment.
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spelling pubmed-42087662014-10-27 Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity Ito, Masaki Hayashi, Kazumi Adachi, Eru Minamisawa, Tamiko Homma, Sadamu Koido, Shigeo Shiba, Kiyotaka PLoS One Research Article Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment. Public Library of Science 2014-10-24 /pmc/articles/PMC4208766/ /pubmed/25343355 http://dx.doi.org/10.1371/journal.pone.0110425 Text en © 2014 Ito 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
Ito, Masaki
Hayashi, Kazumi
Adachi, Eru
Minamisawa, Tamiko
Homma, Sadamu
Koido, Shigeo
Shiba, Kiyotaka
Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity
title Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity
title_full Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity
title_fullStr Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity
title_full_unstemmed Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity
title_short Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity
title_sort combinatorial contextualization of peptidic epitopes for enhanced cellular immunity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208766/
https://www.ncbi.nlm.nih.gov/pubmed/25343355
http://dx.doi.org/10.1371/journal.pone.0110425
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