Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xia, Min, Chen, Daxin, Endresz, Valeria, Lantos, Ildiko, Szabo, Andrea, Kakkar, Vijay, Lu, Xinjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
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
_version_ 1782364583110901760
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
work_keys_str_mv AT xiamin modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice
AT chendaxin modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice
AT endreszvaleria modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice
AT lantosildiko modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice
AT szaboandrea modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice
AT kakkarvijay modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice
AT luxinjie modulationofrecombinantantigenicconstructscontainingmultiepitopestowardseffectivereductionofatheroscleroticlesioninb6129sldlrtm1herapobtm2sgyjmice