A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit

Yi Wei Liaw, Chi Yu Lin, Yu Sheng Lai, Tzu Chung Yang, Chau Jong Wang, Jacqueline Whang-Peng, Leroy F. Liu, Chia Po Lin, Shin Nieh, Shao Chun Lu, Jaulang Hwang

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Article numbere111529
JournalPLoS One
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 8 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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