Clogged arteries (atherosclerosis) is the major cause of heart attacks and strokes worldwide and the primary underlying condition of most cardiovascular diseases. Although high LDL cholesterol levels, poor lifestyle habits and/or genetic disposition are often referred to as the most significant contributors to this disease, recent insights suggest the immune system may play a critical role in drive this disease. Data from the ReNewAthero consortium even suggests atherosclerosis is an auto-immune like disease, in a similar mold as Type I Diabetes, Rheumatoid Arthritis of Multiple Sclerosis, where immune cells attack an individuals own tissue. We hypothesize that by treating atherosclerosis as an auto-immune disease, we can target the root causes of it. We suggest to develop an mRNA vaccine that will train the immune system to stop attacking its own tissue. For this we will first identify which protein are attacked by the immune cells (so called antigens) and will use these antigens to construct a new type of mRNA vaccine. As current mRNA vaccine (such as the SARS-COV2 vaccines) provide the immune systems for instructions to attack antigens, we will first develop an mRNA vaccine formulation that provides the right instruction (tolerogenic vaccines). We assess whether the new vaccines are effective at manipulating the immune system and reducing atherosclerosis using murine and human models of disease. We expect that this approach improve our understanding of atherosclerosis and will accelerated the development of new therapeutics for CVD