Rational Design of Athero-Protective Vaccines; Novel Vaccine Formulations and Alternative Routes of Administration
Atherosclerosis is a chronic inflammatory disease affecting millions of people world-wide.
Atherosclerosis is a chronic inflammatory disease affecting millions of people world-wide. Cells of both the innate and adaptive immune system are present in atherosclerotic plaques, however their exact role in the progression of the disease is not fully understood. The disease is initiated by the influx of immune cells as a response to sub-endothelial retention and the oxidation of low-density lipoproteins (LDLs) in large and medium-sized arteries. Chronic inflammation leads to unstable plaques that can rupture and cause thrombotic events such as ischemia, myocardial infarction or strokes. Experimental vaccination with oxidized LDL (oxLDL)-derived proteins and peptides have been effective at reducing atherosclerosis, but the exact mechanisms of protection are unknown. Furthermore, it is known that using advanced drug delivery methods for specific targeting to antigen presenting cells (APCs) can greatly enhance the therapeutic effects, whilst simultaneously reducing toxicity.
The goal of this project is to design an athero-protective vaccine using advanced drug delivery methods (e.g. nanoparticles, microparticles) and to deliver therapeutic antigens to APCs to elicit specific immune responses (e.g. Th1, Th2, Treg). This approach may develop into a therapy for atherosclerosis, but may also help elucidate the role of the different immune cells in the disease.