Modulation of recombinant Antigenic constructs containing multi-epitopes towards effective reduction of atherosclerotic lesion in B6;129S-Ldlrtm1HerApobtm2Sgy/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...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
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Public Library of Science (PLoS)
2015
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| Sorozat: | PLOS ONE
10 No. 4 |
| doi: | 10.1371/journal.pone.0123393 |
| mtmt: | 2884381 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/10428 |
| Tartalmi kivonat: | 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 [ApoB100688-707 + hHSP60303-312 + hHSP60153-163 + 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" (C5aR1-31) and RPHC with a further "H" (hHSP60303-312) conversion into "P" (protease-activated receptor-142-55) in mice. Antigenic epitopes were incorporated into a dendroaspin scaffold. Immunization of B6;129S-Ldlrtm1HerApobtm2Sgy/J mice with three constructs elicited production of high levels of antibodies against each epitope (apart from hHSP60153-163 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. Copyright: © 2015 Xia et al. |
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| Terjedelem/Fizikai jellemzők: | Terjedelem: 21 p.-Azonosító: e0123393 |
| ISSN: | 1932-6203 |