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公开(公告)号：EP2274619A2
公开(公告)日：2011-01-19
申请号：EP09712022.4
申请日：2009-02-20
申请人： Universiteit Gent
IPC分类号： G01N33/68
CPC分类号： A61K47/48415 , A61K9/0053 , A61K39/002 , A61K39/0258 , A61K39/3955 , A61K47/6811 , A61K47/6849 , A61K47/6913 , A61K47/6927 , A61K47/6929 , A61K2039/542 , A61K2039/6056 , G01N33/573 , G01N2333/705 , G01N2333/948 , G01N2500/04
摘要： The invention is based on the identification of aminopeptidase N (APN) as the receptor for F4 fimbriae of enterotoxigenic E. coli (ETEC). Based on the observation that oral administration of F4 fimbriae induces a protective intestinal mucosal immune response against a subsequent challenge with F4 ETEC, and the observation that the internalization of said F4 fimbriae is clathrin-mediated, the present invention provides the characterization of APN as a target useful in: in an in vitro assay to screen for molecules that are capable to mimic the clathrin-mediated F4 endocytosis; in an in vitro assay to screen for molecules that are capable to modulate the binding of F4 fimbriae with APN; in the development of a carrier for the delivery of antigens/therapeutics, i.e. immunomodulators to the intestinal submucosa or the intestinal mucosa-associated lymphoid tissue, wherein said carrier comprises an APN specific target molecule that mimics the clathrin-mediated F4 endocytosis. The use of the carriers thus identified or the treatments thus identified, in a method of inducing an antigen specific intestinal mucosal immune response, and/or in the treatment of bacterial diarrhea, is a further aspect of the present invention.
摘要翻译： 本发明基于氨肽酶N（APN）作为肠毒素大肠杆菌（ETEC）的F4菌毛的受体的鉴定。 基于观察到F4菌毛的口服施用诱导针对随后的F4ETEC攻击的保护性肠粘膜免疫应答，并且观察到所述F4菌毛的内化是网格蛋白介导的，本发明提供了将APN表征为 目标用于：在体外测定中筛选能够模拟网格蛋白介导的F4内吞作用的分子; 在体外测定中筛选能够调节F4菌毛与APN结合的分子; 在开发将抗原/治疗剂即免疫调节剂递送至肠粘膜下层或肠粘膜相关淋巴组织的载体的开发中，其中所述载体包含模拟网格蛋白介导的F4内吞作用的APN特异性靶分子。 在诱导抗原特异性肠粘膜免疫应答的方法中和/或在治疗细菌性腹泻中使用如此鉴定的载体或由此鉴定的治疗方法是本发明的另一个方面。
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公开(公告)号：EP2274619B1
公开(公告)日：2013-06-05
申请号：EP09712022.4
申请日：2009-02-20
申请人： Universiteit Gent
IPC分类号： G01N33/573
CPC分类号： A61K47/48415 , A61K9/0053 , A61K39/002 , A61K39/0258 , A61K39/3955 , A61K47/6811 , A61K47/6849 , A61K47/6913 , A61K47/6927 , A61K47/6929 , A61K2039/542 , A61K2039/6056 , G01N33/573 , G01N2333/705 , G01N2333/948 , G01N2500/04
摘要： The invention is based on the identification of aminopeptidase N (APN) as the receptor for F4 fimbriae of enterotoxigenic E. coli (ETEC). Based on the observation that oral administration of F4 fimbriae induces a protective intestinal mucosal immune response against a subsequent challenge with F4 ETEC, and the observation that the internalization of said F4 fimbriae is clathrin-mediated, the present invention provides the characterization of APN as a target useful in: in an in vitro assay to screen for molecules that are capable to mimic the clathrin-mediated F4 endocytosis; in an in vitro assay to screen for molecules that are capable to modulate the binding of F4 fimbriae with APN; in the development of a carrier for the delivery of antigens/therapeutics, i.e. immunomodulators to the intestinal submucosa or the intestinal mucosa-associated lymphoid tissue, wherein said carrier comprises an APN specific target molecule that mimics the clathrin-mediated F4 endocytosis. The use of the carriers thus identified or the treatments thus identified, in a method of inducing an antigen specific intestinal mucosal immune response, and/or in the treatment of bacterial diarrhea, is a further aspect of the present invention.
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