Two decades of vaccine development against atherosclerosis

Atherosclerosis is an immune-mediated chronic inflammatory disease that leads to the development of fatty plaques in the arterial walls, ultimately increasing the risk of thrombosis, stroke, and myocardial infarction. The immune response in this complex disease is both atheroprotective and pro-atherogenic, involving both innate and adaptive immunity. Current treatments include the adjustment of lifestyle factors, cholesterol-lowering drugs such as statins, and immunotherapy, whereas vaccine development has received comparatively little attention. In this review, we discuss the potential of antigen-specific vaccination as a preventative approach based on more than 20 years of research and innovation. Vaccination targets include proteins that are more abundant in atherosclerotic patients, such as oxidized low-density lipoprotein (LDL), apolipoprotein B-100, proprotein convertase subtilisin/kexin type-9 serine protease (PCSK9), cholesteryl ester transfer protein (CETP), and heat shock proteins HSP60 and HSP65. Immunization with such proteins or their peptide epitopes has been shown to induce T-cell activation, produce antigen-specific antibodies, reduce the size of atherosclerotic lesions, and/or reduce serum cholesterol levels. Vaccination against atherosclerosis therefore offers a new strategy to address the burden on healthcare systems caused by cardiovascular disease, the leading cause of death worldwide.