Vaccines modulating lipoprotein autoimmunity as a possible future therapy for cardiovascular disease

Current strategies for prevention of cardiovascular disease focus on risk factor intervention. Although these have been proven both safe and effective results from randomized clinical trials suggest that it is difficult to achieve relative risk reductions exceeding 40% with this approach. To further improve efficacy future therapies must aim at targeting the actual disease process in the arterial wall. Emerging evidence have identified an important role of the immune system in atherosclerosis and suggest that modulation of autoimmune responses against oxidized LDL and other antigens in the atherosclerotic plaque represent one possible new approach to disease prevention. Oxidized LDL is targeted by both antibody-mediated and cellular immune responses and as much as 10% of the T cells in atherosclerotic plaques are oxidized LDL-specific. Immune activation in the atherosclerotic plaque is primarily of the pro-inflammatory Th1-type and inhibition Th1 immunity reduces atherosclerosis in experimental animals. Atherosclerosis vaccines based on antigens derived from LDL have been developed to modulate these processes. Their mechanisms of action remain to be full characterized but may involve expression of protective antibodies that facilitate the removal of oxidized LDL and antigen-specific regulatory T cells that counteract Th1 autoimmunity against oxidized LDL. In this review we will discuss the possibilities and challenges encountering the translation of immune-modulatory therapy for atherosclerosis from the experimental stage into the clinic.