A biologics targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis (NASH) in rabbit.

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, Taivital Biopharmaceutical Co. LTD. have successfully developed a novel anti-CETP biologics (Fc-CETP6) to overcome the low immunogenicity of CETP and for long-term inhibition of CETP activity. The anti-CETP biologics 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 anti-CETP biologics. The Fc-CETP6 anti-CETP biologics 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 anti-CETP biologics 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 anti-CETP biologics may improve atherosclerosis and NASH and has high potential for clinical use.

 
Reference:
Liaw Yi-Wei, Lin Chi-Yu, Lai Yu-Sheng, Yang Tzu-Chung, Wang Chau-Jong, Whang-Peng J., Liu Leroy F, Lin Chia-Po, Nieh Shin, Lu Shao-Chun, Hwang J. A vaccine targeted at CETP alleviates high fat and high cholesterol diet-induced atherosclerosis and non-alcoholic steatohepatitis in rabbit. PLoS ONE; 2014, 9(12): e111529. doi:10.1371/journal.pone.0111529