title: A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit.
abstract: Low HDL-C levels are associated with atherosclerosis and non-alcoholic steatohepatitis, and increased levels may reduce the risk of these diseases. Inhibition of cholesteryl ester transfer protein (CETP) activity is considered a promising strategy for increasing HDL-C levels. Since CETP is a self-antigen with low immunogenicity, we developed a novel CETP vaccine (Fc-CETP6) to overcome the low immunogenicity of CETP and for long-term inhibition of CETP activity. The vaccine consists of a rabbit IgG Fc domain for antigen delivery to antigen-presenting cells fused to a linear array of 6 repeats of a CETP epitope to efficiently activate B cells. Rabbits were fed a high fat/cholesterol (HFC) diet to induce atherosclerosis and NASH, and immunized with Fc-CETP6 vaccine. The Fc-CETP6 vaccine successfully elicited anti-CETP antibodies and lowered plasma CETP activity. The levels of plasma HDL-C and ApoA-I were higher, and plasma ox-LDL lower, in the Fc-CETP6-immunized rabbits as compared to the unimmunized HFC diet-fed rabbits. Pathological analyses revealed less lipid accumulation and inflammation in the aorta and liver of the Fc-CETP6-immunized rabbits. These results show that the Fc-CETP6 vaccine efficiently elicited antibodies against CETP and reduced susceptibility to both atherosclerosis and steatohepatitis induced by the HFC diet. Our findings suggest that the Fc-CETP6 vaccine may improve atherosclerosis and NASH and has high potential for clinical use.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan; Department of Biochemistry, Medical College, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Liaw
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Biochemistry, Medical College, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lai
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Tzu-Chung
authors.initials: TC
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whang-Peng
authors.affiliation: Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan; Department of Pharmacology, The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey, United States of America.
authors.forename: Leroy F
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Division of Drug Biology, Bureau of Food and Drug Analysis, Department of Health, Executive Yuan, Taiwan.
authors.forename: Chia-Po
authors.initials: CP
authors.lastname: Lin
authors.affiliation: Department of Pathology, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nieh
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Lu
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan; Department of Biochemistry, Medical College, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jaulang
authors.initials: J
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014612:Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D007141:Immunoglobulin Fc Fragments; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C099252:oxidized low density lipoprotein; D002784:Cholesterol