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| Immunology Effects of Anti-atherosclerosis Protein Vaccines Based on Heat Shock Protein 65 |
| SUN Yun-xiao1,2, LU Yong1, LI Zhu-fang1, XU Qiang2, LIU Xiao-ming2, LI Tai-ming1, LIU Jing-jing1 |
1. Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China;
2. Research and Development Center of Nonhuman Primates, South China Institute of Endangered Animals, Guangzhou 510260, China |
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Abstract By using two functional epitopes of HSP65 with preventive effects to autoimmune inflammatory disease, high-level expression vectors of pET28a-HSP65-P1P2P1 and pET28a-CTB-P1P2P1 were built with HSP65 and CTB as a carrier protein respectively. The fusion protein of HSP65-P1P2P1 and CTB-P1P2P1 were acquired by anion exchange column chromatography and then used to immunize the New Zealand white rabbits with atherosclerosis disease induced by high cholesterol diet-fed. The animals were nasally immunized with low-dose proteins for multiple times. The results showed that two groups of fusion proteins possessed the effectiveness of reducing atherosclerotic plaque formation. Compared with the PBS control group the aortic lesion areas of the two groups decreased by 34.9% and 27.9% separately. The study provided a good design idea for the further development of clinical anti-AS vaccine. After further optimization design for increasing their immunogenicity, it could be developed as a vaccine against atherosclerosis.
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Received: 11 August 2010
Published: 25 January 2011
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[1] Witebsky E, Rose N R, Shulman S. Studies of normal and malignant tissue antigens. Cancer Res, 1956, 16 (9):831-841.
[2] Pereira I A, Borba E F. The role of inflammation, humoral and cell mediated autoimmunity in the pathogenesis of atherosclerosis. Swiss Med Wkly, 2008, 138(37-38):534-539.
[3] Shoenfeld Y, Sherer Y, Harats D. Artherosclerosis as an infectious, inflammatory and autoimmune disease. Trends Immunol, 2001, 22(6):293-295.
[4] Matsuura E, Kobayashi K, Lopez L R. Atherosclerosis in autoimmune diseases. Curr Rheumatol Rep, 2009, 11(1):61-69.
[5] Xu Q. Role of heat shock proteins in atherosclerosis. Arterioscler Thromb Vasc Biol,2002, 22(10):1547-1559.
[6] Wick G. Atherosclerosis-an autoimmune disease due to an immune reaction against heat-shock protein 60. Herz, 2000, 25(2):87-90.
[7] Pockley A G. Heat shock proteins, inflammation, and cardiovascular disease. Circulation, 2002, 105(8):1012-1017.
[8] Maron R, Sukhova G, Faria A M, et al. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation, 2002, 106(13): 1708-1715.
[9] Metzler B,Mayr M, Dietrich H, et al. Inhibition of arteriosclerosis by T-cell depletion in normocholesterolemic rabbits immunized with heat shock protein 65. Arterioscler Thromb Vasc Biol, 1999, 19(8):1905-1911.
[10] 李祝方,龙军,孙云霄,等. 热休克蛋白65及其两个功能表位在调节动脉粥样硬化中的作用. 药物生物技术, 2009, 16(1):1-7. Li Z F, Long J, Sun Y X, et al.Pharmaceutical Biotechnology,2009, 16(1):1-7.
[11] Quintana F J, Carmi P, Mor F, et al. DNA fragments of the human 60-kDa heat shock protein (HSP60) vaccinate against adjuvant arthritis: identification of a regulatory HSP60 peptide. J Immunol, 2003, 171(7): 3533-3541.
[12] Ulmansky R, Cohen C J, Szafer F, et al. Resistance to adjuvant arthritis is due to protective antibodies against heat shock protein surface epitopes and the induction of IL-10 secretion. J Immunol, 2002, 168(12): 6463-6469.
[13] Harats D, Yacov N, Gilburd B, et al.Oral tolerance with heat shock protein 65 attenuates Mycobacterium tuberculosis-Induced and high-fat-diet-driven atherosclerotic lesions. J Am Coll Cardiol, 2002, 40(7):1333-1338.
[14] 李建平,熊祺琰,陈庆梅,等.霍乱毒素B亚单位与p277融合基因在大肠杆菌中表达及免疫分析. 药物生物技术, 2007, 14(3):157-163. Li J P, Xiong Q Y, Chen Q M, et al.Phamaceutical Biotechnology, 2007, 14 (3): 157-163.
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