Home > Therapeutic vaccines > Atherosclerosis
The term atherosclerosis describes a chronic disease which is colloquially known as “hardening of the arteries”. Predominantly white blood cells and blood platelets are involved in multiple inflammatory processes leading to deposits of particles and proliferation of connective tissue and muscle cells. Plaques composed of mainly cholesterol and other lipids, inflammatory cells, and calcium deposits lead to a thickening and hardening of the blood vessels. Initially, this is not noticed for many years but leads to increasing narrowing and reduced elasticity of the blood vessels. The blood supply is reduced and may even be completely halted.
Depending on the vessels and organs affected, the result can be cardiovascular disease such as coronary infarction, stroke or peripheral vascular disease (“smoker’s leg”). The diseases caused by atherosclerosis remain at ~50% the most common cause of death in the western world. The main risk factor is the modern western lifestyle: Little physical exercise, poor diet and smoking can lead to obesity (increased abdominal fat is particularly damaging), elevated blood pressure, problems with the fat metabolism and diabetes. Some people also suffer from congenital fat metabolism disorders (for example familial hypercholesteremia).
45% of coronary infarctions in Western Europe are caused by abnormal blood lipids (source: INTERHEART study) and cardiovascular disease is the main cause of death in Europe. The combination of elevated LDL cholesterol values (low density lipoprotein cholesterol) and low HDL cholesterol values (high density lipoprotein cholesterol) is the main cause of this problem. Even a lasting change in lifestyle is insufficient for many patients. The currently most important pharmacological therapies that influence fat metabolism (statins) mainly lower the “bad” LDL cholesterol. Nicotinic acid beneficially influences HDL cholesterol levels but may not be taken regularly by those affected because of their unpleasant side effects. However, an additional increase in “good” HDL cholesterol is also necessary to definitely reduce the risk of atherosclerosis. Because: No matter how high or low the LDL cholesterol is, the quantity of vessel-protecting HDL cholesterol is a risk factor for cardiovascular disease independent of LDL cholesterol.
An important therapeutic aim is therefore to increase the HDL cholesterol.
The atherosclerosis vaccine developed by AFFiRiS targets a key protein called CETP (cholesterol ester transfer protein), the inhibition of which causes an effective change in the ratio of LDL to HDL cholesterol. CETP is a plasma protein which is responsible for the transfer of neutral lipids and phospholipids between lipoproteins and reduces the plasma concentration of HDL cholesterol. Inhibition of CETP in animal models leads to an increase in HDL cholesterol and less atherosclerotic lesions and represents a very promising target for the AFFITOME® technology.
The vaccine is currently in advanced pre-clinical development and will induce specific antibodies to this complex endogenous protein.
Atherosclerosis is a chronic disease. In contrast to the currently available drugs, a vaccine offers the crucial advantage that it is only administered on a few occasions and does not have to be taken continuously like drugs. It could therefore also make a significant contribution to reducing the considerable costs to the health system caused by this disease.
The financing for the atherosclerosis project was initially provided by ZIT (centre for innovation and technology in the city of Vienna) as part of the Call FemPower 2004. The project achieved first place in this Call. Currently, the CETP vaccine project is supported by an EU grant (ETB-2008-28).
