Induction of cellular immunity against TIE2 by DNA vaccination attenuates atherosclerosis

TIE2 positive cels play a crucial role in processes that are potentialy involved in atherosclerosis, such as angiogenesis. Therefore, the specific deletion of TIE2 positive cels by means of DNA vaccination may affect atherosclerosis. Celular immunity against cels that overexpress TIE2 was established in LDLr -/mice by a novel oral DNA vaccination technique, in which an attenuated Salmonella typhimurium strain was used as a carrier for plasmid pcDNA3.1 encoding TIE2. After three oral vaccinations with 2-week time intervals LDLr -/mice were put on a Western type diet and atherosclerosis was induced. Eight weeks after vaccination FACS analysis of circulating PBMCs revealed a significant decrease (33%, p<0.05) in TIE2 positive cels upon vaccination against TIE2, indicating the successful induction of celular immunity folowing vaccination against TIE2. Six weeks after colar placement vaccination against TIE2 resulted in significantly decreased carotid atherosclerosis, as indicated by 30% (p<0.05) reduced intima area and 27% (p<0.05) reduced intima/lumen ratios. Furthermore, atherosclerosis was attenuated in the aortic root by 42% (p<0.05), confirming the anti-atherosclerotic effect of vaccination against TIE2. Histochemical analysis of the atherosclerotic lesion composition revealed a 1.6-fold (p<0.05) increase in colagen content upon vaccination against TIE2, indicating a more stable plaque phenotype. We demonstrate that vaccination against TIE2 induced celular immunity against cels that overexpress TIE2 and resulted in smaler atherosclerotic lesions with a more stable phenotype. Therefore, vaccination strategies that target cels that contribute to atherosclerosis, may be of potential use in the development of novel treatments against atherosclerosis. Chapter 7