Active immunization using TRPM2 peptide vaccine attenuates atherosclerotic progression in a mouse model of atherosclerosis

Abstract

Atherosclerosis is one of the leading causes of cardiovascular diseases and mortality around the world. One exciting strategy for atherosclerosis treatment is immunotherapy, especially active immunization. Active immunization relies on the delivery of antigens in a vaccine platform to introduce humoral and cellular immunity alleviating atherosclerotic progression. TRPM2 is an ROS-activated Ca2+-permeable ion channel that can promote atherosclerosis via stimulating vascular inflammation. In the present study, we developed a strategy of active immunization with TRPM2 E3 domain peptide in a vaccine platform, aiming to induce endogenous production of anti-TRPM2 blocking antibody in mice in vivo, consequently inhibiting TRPM2 channel activity to alleviate atherosclerotic progression. The results show that immunization with a pig TRPM2 E3 region-based peptide (P1) could effectively alleviate high cholesterol diet-induced atherosclerosis in ApoE-/- mice. We worked out the best vaccine formulation for most effective atheroprotection, namely P1 at the dose of 67.5 µg per mouse (2.5 mg/kg body weight) with aluminium salts as adjuvant. The present study laid the foundation for future clinical trials using TRPM2 E3 vaccine for potential therapeutic option against atherosclerosis.