A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit
Journal
PLoS ONE
Journal Volume
9
Journal Issue
12
Date Issued
2014
Author(s)
Liaw Y.-W.
Lin C.-Y.
Lai Y.-S.
Yang T.-C.
Wang C.-J.
Whang-Peng J.
Liu L.F.
Lin C.-P.
Nieh S.
SHAO-CHUN LU
Hwang J.
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. ? 2014 Liaw et al.
SDGs
Other Subjects
apolipoprotein A1; cholesterol; cholesterol ester transfer protein; cholesterol ester transfer protein antibody; fc cholesterol ester transfer protein 6 vaccine; high density lipoprotein cholesterol; oxidized low density lipoprotein; protein antibody; unclassified drug; vaccine; antibody; apolipoprotein A1; cholesterol; cholesterol ester transfer protein; hybrid protein; immunoglobulin Fc fragment; low density lipoprotein; oxidized low density lipoprotein; vaccine; animal cell; animal experiment; animal model; animal tissue; antibody production; aortic inflammation; Article; atherosclerosis; cholesterol blood level; cholesterol diet; controlled study; drug efficacy; enzyme activity; female; hepatitis; immunization; immunogenicity; inflammation; lipid diet; lipid storage; lipoprotein blood level; liver fibrosis; macrophage migration; nonalcoholic fatty liver; nonhuman; protein blood level; adverse effects; animal; atherosclerosis; blood; disease model; fibrosis; gene expression; genetics; human; immunology; lipid diet; metabolism; Non-alcoholic Fatty Liver Disease; pathology; rabbit; Oryctolagus cuniculus; Animals; Antibodies; Apolipoprotein A-I; Atherosclerosis; Cholesterol; Cholesterol Ester Transfer Proteins; Diet, High-Fat; Disease Models, Animal; Female; Fibrosis; Gene Expression; Humans; Immunoglobulin Fc Fragments; Lipoproteins, LDL; Non-alcoholic Fatty Liver Disease; Rabbits; Recombinant Fusion Proteins; Vaccines
Publisher
Public Library of Science
Type
journal article