A chimeric peptide of intestinal trefoil factor containing cholesteryl ester transfer protein B cell epitope significantly inhibits atherosclerosis in rabbits after oral administration

Vaccination against cholesteryl ester transfer protein (CETP) is proven to be effective for inhibiting atherosclerosis in animal models. In this study, the proteases-resistant intestinal trefoil factor (TFF3) was used as a molecular vehicle to construct chimeric TFF3 (cTFF3) containing CETP B cell epitope and tetanus toxin helper T cell epitope. It was found that cTFF3 still preserved a trefoil structure, and can resist proteases digestion in vitro. After oral immunization with cTFF3, the CETP-specific IgA and IgG could be found in intestine lavage fluid and serum, and the anti-CETP antibodies could inhibit partial CETP activity to increase high-density lipoprotein cholesterol, decrease low-density lipoprotein cholesterol, and inhibit atherosclerosis in animals. Therefore, TFF3 is a potential molecular vehicle for developing oral peptide vaccines. Our research highlights a novel strategy for developing oral peptide vaccines in the future.

Research highlights▶ The chimeric ITF containing CETP B cell epitope can form the correct trefoil structure. ▶ The chimeric ITF can resist the proteases digestion in vitro assay. ▶ The chimeric ITF can induce both of mucosal and systemic immune response in rabbits after oral administration. ▶ The anti-CETP antibodies induced by oral vaccination with cITF can inhibit CETP activity, increase HDL-C, decrease LDL-C and inhibit atherosclerosis in rabbits.