Atherosclerosis, especially coronary heart disease (CHD), remains a most significant global public health problem. Highly effective LDL-lowering therapies have gained widespread adoption in the United States and throughout the developed world, but therapeutic options for raising low HDL, a key independent risk factor for CHD, remain limited. We are developing a vaccine approach to raising HDL, by inducing an immune response to endogenous cholesteryl ester transfer protein (CETP), and have demonstrated proof of principle in preclinical and clinical models. This vaccine approach may offer the opportunity to address low HDL with a cost-effective semi-annual injection.