Impact of multiple antigenic epitopes from ApoB100, hHSP60 and Chlamydophila pneumoniae on atherosclerotic lesion development in Apob^tm2SgyLdlr^tm1Her J mice

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• 作者：Xinjie Lu ; Min Xia ; Valeria Endresz ; Ildiko Faludi ; Andrea Szabo ; Eva Gonczol ; Lakshmi Mundkur ; Daxin Chen ; Vijay Kakkar
• 关键词：Immunization ; ApoB-100 ; hHSP60 ; C. pneumoniae ; Atherosclerosis
• 刊名：Atherosclerosis
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：225
• 期：1
• 页码：56-68
• 全文大小：3238 K

文摘

Aims

To assess whether immunizing Apob^tm2SgyLdlr^tm1Her J mice simultaneously with different atherosclerosis-related epitopes engineered in a single recombinant protein is effective in reducing atherosclerotic lesions.

Methods and results

Antigenic epitopes were incorporated into a dendroaspin scaffold: AHC (ApoB100 peptide?+?hHSP60 peptide [hHSP60_153-163]?+?putative epitope derived from Chlamydophila pneumoniae [Cpn]) and AHHC (AHC?+?hHSP60_303-312); and were compared with construct A (ApoB peptide), construct H (hHSP60_153-163), and construct AH (ApoB100 peptide?+?hHSP60_153-163). Immunization with 2 multiple-antigenic epitope constructs elicited high levels of antibodies against each epitope in Apob^tm2SgyLdlr^tm1Her J mice (apart from hHSP60_153-163, which induced a low antibody response). Histological analyses demonstrated that the mice immunized with AHHC and AHC showed significant reductions in the size of atherosclerostic lesions compared with controls (63.8 % and 63.2 % ; P?<?0.001, respectively), and significantly greater reductions in lesions size compared with those after immunization with construct A (24.9 % ; P?<?0.01), H (26.8 % ; P?<?0.05), and AH (42.9 % ; P?<?0.001). Moreover, combination of 2 short Cpn peptides along with ApoB and hHSP60 peptides had an additive effect on reducing the lesion without Cpn infection. Reduction in plaque size correlated with cellular infiltration and cytokine/chemokine secretion in serum or by stimulated spleen cells as well as specific cellular immune responses when compared with controls.

Conclusions

Immunization of mice with a single construct containing multiple epitopes derived from ApoB100, hHSP60 and Cpn was more effective in reducing early atherosclerotic lesions through the induction of a specific Treg-cell response than was the construct containing either mono- or bi-epitopes. This approach offers attractive opportunities for the design of protein-based, multivalent vaccines against atherosclerosis.