展示Sap2表位的杂合噬菌体对白色念珠菌感染小鼠的免疫保护作用

发布时间：2018-05-19 14:19

本文选题：系统性白色念珠菌感染 + Sap2　；参考：《东北师范大学》2011年硕士论文

【摘要】：白色念珠菌是一种寄生于正常机体中的机会致病真菌,当机体免疫力低下或者正常菌群失调的情况下,就会转变为致病菌。分泌型天冬氨酸蛋白酶2(Sap2)是白色念珠菌分泌的一种毒性因子。作为一种免疫优势抗原,研究表明,Sap2在动物抵抗白色念珠菌感染的过程中有显著免疫保护作用,并且抗Sap2的抗体对白色念珠菌感染动物的被动治疗也有明显作用。噬菌体作为一种新型多肽载体,在免疫学中有着很重要的作用。本课题组已经把Sap2的两个抗原表位即VKYTS和SLAQVKYTSASS分别展示在了噬菌体上,本实验研究了这两种杂合噬菌体对小鼠在白色念珠菌感染中的免疫保护作用,同时研究了抗这两种杂合噬菌体的抗体对白色念珠菌感染小鼠的被动免疫治疗作用。将Sap2重组蛋白、展示VKYTS的杂合噬菌体、展示SLAQVKYTSASS的杂合噬菌体和野生噬菌体分别通过腹腔免疫BALB/c小鼠,然后从免疫小鼠血清中得到了高效价的抗体,说明噬菌体作为多肽载体在没有佐剂的情况下就可以诱导机体产生强烈免疫应答。免疫四次之后的小鼠以安全浓度(2×106个细胞/只小鼠)的白色念珠菌ATCC10231尾静脉感染,观察肝脏、肾脏中的病理学变化,结果发现分别展示了Sap2的两个表位的杂合噬菌体与重组型Sap2蛋白一样能够对白色念珠菌感染小鼠起到一定的免疫保护作用。感染了白色念珠菌ATCC10231(2×107个细胞/只小鼠)的小鼠用抗血清通过尾静脉给以被动免疫治疗,研究发现,分别展示了Sap2的两个表位的杂合噬菌体抗体与重组型Sap2蛋白抗体一样能够对白色念珠菌感染小鼠起到一定的被动免疫治疗作用。
[Abstract]:Candida albicans is a opportunistic fungus parasitic on normal organisms, which can be transformed into pathogenic bacteria when the immunity of the body is low or the normal flora is disordered. Secretory aspartate protease 2 (Sap2) is a toxic factor secreted by Candida albicans. As an immune dominant antigen, Sap2 has a significant protective effect in the process of resistance to Candida albicans infection in animals, and the antibody against Sap2 also plays an important role in the passive treatment of Candida albicans infection in animals. As a new polypeptide carrier, phage plays an important role in immunology. The two antigenic epitopes of Sap2, VKYTS and SLAQVKYTSASS, have been displayed on phage respectively. The immune protection of these two hybrid phages against Candida albicans infection in mice was studied. At the same time, the passive immunotherapeutic effects of antibodies against these two hybrids on mice infected with Candida albicans were studied. The Sap2 recombinant protein was used to display the hybrid phage of VKYTS, the hybrid phage of SLAQVKYTSASS and the wild phage were immunized intraperitoneally respectively with BALB/c mice, then the antibody with high titer was obtained from the serum of immunized mice. The results showed that phage could induce a strong immune response without adjuvant. The mice were immunized with 2 脳 106 cells / mouse of safe concentration of Candida albicans ATCC10231 tail vein infection, and the pathological changes in liver and kidney were observed. The results showed that the hybrid phage with two epitopes of Sap2, like recombinant Sap2 protein, could protect mice against Candida albicans infection. Mice infected with Candida albicans ATCC10231(2 脳 107 cells / mouse) were given passive immunotherapy via tail vein with antiserum. The results showed that the hybrid phage antibody of two epitopes of Sap2 could play a passive immunotherapy effect on mice infected with Candida albicans as well as recombinant Sap2 protein antibody.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R392

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