title: Impact of multiple antigenic epitopes from ApoB100, hHSP60 and Chlamydophila pneumoniae on atherosclerotic lesion development in Apob(tm2Sgy)Ldlr(tm1Her)J mice.
abstract: OBJECTIVE
  To assess whether immunizing Apob(tm2Sgy)Ldlr(tm1Her)J mice simultaneously with different atherosclerosis-related epitopes engineered in a single recombinant protein is effective in reducing atherosclerotic lesions.
  
  
  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(tm2Sgy)Ldlr(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.
authors.affiliation: The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, United Kingdom. xlu@tri-london.ac.uk
authors.forename: Xinjie
authors.initials: X
authors.lastname: Lu
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Valeria
authors.initials: V
authors.lastname: Endresz
authors.forename: Ildiko
authors.initials: I
authors.lastname: Faludi
authors.forename: Andrea
authors.initials: A
authors.lastname: Szabo
authors.forename: Eva
authors.initials: E
authors.lastname: Gonczol
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Mundkur
authors.forename: Daxin
authors.initials: D
authors.lastname: Chen
authors.forename: Vijay
authors.initials: V
authors.lastname: Kakkar
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D053299:Apolipoprotein B-100 / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004546:Elapid Venoms / Q000737:chemistry / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007114:Immunization; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D053299:Apolipoprotein B-100; D018834:Chaperonin 60; D004546:Elapid Venoms; D000939:Epitopes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074772:mambin