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Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice
Atherosclerosis is increasingly recognized as a complex chronic inflammatory disease. Many more studies have extended vaccination against atherosclerosis by using epitopes from self-antigens or beyond and demonstrated that vaccination with antigens or derivatives could reduce the extent of the lesio...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382319/ https://www.ncbi.nlm.nih.gov/pubmed/25830298 http://dx.doi.org/10.1371/journal.pone.0123393 |
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author | Xia, Min Chen, Daxin Endresz, Valeria Lantos, Ildiko Szabo, Andrea Kakkar, Vijay Lu, Xinjie |
author_facet | Xia, Min Chen, Daxin Endresz, Valeria Lantos, Ildiko Szabo, Andrea Kakkar, Vijay Lu, Xinjie |
author_sort | Xia, Min |
collection | PubMed |
description | Atherosclerosis is increasingly recognized as a complex chronic inflammatory disease. Many more studies have extended vaccination against atherosclerosis by using epitopes from self-antigens or beyond and demonstrated that vaccination with antigens or derivatives could reduce the extent of the lesions in atherosclerosis-prone mice. Our previous study has demonstrated that construct AHHC [ApoB100(688-707) + hHSP60(303-312) + hHSP60(153-163) + Cpn derived peptide (C)] significantly reduced atherosclerotic lesion. The aim of this study was to investigate whether AHHC can be modulated towards increased lesion reduction in mice by creating two other derivatives with a sequential epitope-substitution named RHHC in which A was replaced by an “R” (C5aR(1-31)) and RPHC with a further “H” (hHSP60(303-312)) conversion into “P” (protease-activated receptor-1(42-55)) in mice. Antigenic epitopes were incorporated into a dendroaspin scaffold. Immunization of B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J mice with three constructs elicited production of high levels of antibodies against each epitope (apart from hHSP60(153-163) and P which induced a low antibody response). Histological analyses demonstrated that the mice immunized with either RPHC or RHHC showed significant reductions in the size of atherosclerostic lesions compared to those with AHHC (69.5±1.1% versus 55.7±3.4%, P<0.01 or 65.6±1.3% versus 55.7±3.4%, P<0.01). Reduction of plaque size in the aortic sinus and descending aorta correlated with alterations in cellular immune responses when compared with controls. We conclude that a recombinant construct RPHC may provide new antigenic and structural features which are favorable for significant reduction in atherosclerotic lesion formation. This approach offers a novel strategy for developing anti-atherosclerotic agents. |
format | Online Article Text |
id | pubmed-4382319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43823192015-04-09 Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice Xia, Min Chen, Daxin Endresz, Valeria Lantos, Ildiko Szabo, Andrea Kakkar, Vijay Lu, Xinjie PLoS One Research Article Atherosclerosis is increasingly recognized as a complex chronic inflammatory disease. Many more studies have extended vaccination against atherosclerosis by using epitopes from self-antigens or beyond and demonstrated that vaccination with antigens or derivatives could reduce the extent of the lesions in atherosclerosis-prone mice. Our previous study has demonstrated that construct AHHC [ApoB100(688-707) + hHSP60(303-312) + hHSP60(153-163) + Cpn derived peptide (C)] significantly reduced atherosclerotic lesion. The aim of this study was to investigate whether AHHC can be modulated towards increased lesion reduction in mice by creating two other derivatives with a sequential epitope-substitution named RHHC in which A was replaced by an “R” (C5aR(1-31)) and RPHC with a further “H” (hHSP60(303-312)) conversion into “P” (protease-activated receptor-1(42-55)) in mice. Antigenic epitopes were incorporated into a dendroaspin scaffold. Immunization of B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J mice with three constructs elicited production of high levels of antibodies against each epitope (apart from hHSP60(153-163) and P which induced a low antibody response). Histological analyses demonstrated that the mice immunized with either RPHC or RHHC showed significant reductions in the size of atherosclerostic lesions compared to those with AHHC (69.5±1.1% versus 55.7±3.4%, P<0.01 or 65.6±1.3% versus 55.7±3.4%, P<0.01). Reduction of plaque size in the aortic sinus and descending aorta correlated with alterations in cellular immune responses when compared with controls. We conclude that a recombinant construct RPHC may provide new antigenic and structural features which are favorable for significant reduction in atherosclerotic lesion formation. This approach offers a novel strategy for developing anti-atherosclerotic agents. Public Library of Science 2015-04-01 /pmc/articles/PMC4382319/ /pubmed/25830298 http://dx.doi.org/10.1371/journal.pone.0123393 Text en © 2015 Xia 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 Xia, Min Chen, Daxin Endresz, Valeria Lantos, Ildiko Szabo, Andrea Kakkar, Vijay Lu, Xinjie Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice |
title | Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice |
title_full | Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice |
title_fullStr | Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice |
title_full_unstemmed | Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice |
title_short | Modulation of Recombinant Antigenic Constructs Containing Multi-Epitopes towards Effective Reduction of Atherosclerotic Lesion in B6;129S-Ldlr(tm1Her)Apob(tm2Sgy)/J Mice |
title_sort | modulation of recombinant antigenic constructs containing multi-epitopes towards effective reduction of atherosclerotic lesion in b6;129s-ldlr(tm1her)apob(tm2sgy)/j mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382319/ https://www.ncbi.nlm.nih.gov/pubmed/25830298 http://dx.doi.org/10.1371/journal.pone.0123393 |
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