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

21 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

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cholesteryl ester transfer protein
Cholesterol Ester Transfer Proteins
High Fat Diet
Fatty Liver
high fat diet
Nutrition
atherosclerosis
Atherosclerosis
Vaccines
rabbits
Fats
Cholesterol
vaccines
Rabbits
lipids
cholesterol
Plasmas
immune response
diet
antigens

ASJC Scopus subject areas

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

Cite this

A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit. / Liaw, Yi Wei; Lin, Chi Yu; Lai, Yu Sheng; Yang, Tzu Chung; Wang, Chau Jong; Whang-Peng, Jacqueline; Liu, Leroy F.; Lin, Chia Po; Nieh, Shin; Lu, Shao Chun; Hwang, Jaulang.

In: PLoS One, Vol. 9, No. 12, e111529, 08.12.2014.

Research output: Contribution to journalArticle

Liaw, Yi Wei ; Lin, Chi Yu ; Lai, Yu Sheng ; Yang, Tzu Chung ; Wang, Chau Jong ; Whang-Peng, Jacqueline ; Liu, Leroy F. ; Lin, Chia Po ; Nieh, Shin ; Lu, Shao Chun ; Hwang, Jaulang. / A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit. In: PLoS One. 2014 ; Vol. 9, No. 12.
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AU - Wang, Chau Jong

AU - Whang-Peng, Jacqueline

AU - Liu, Leroy F.

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AU - Nieh, Shin

AU - Lu, Shao Chun

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