Mucosal membrane receptor and uses thereof

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 F4fimbriae 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.

主权项

1. A method of delivering a heterologous antigen or therapeutic molecule across the intestinal mucosal barrier of a subject, said method comprising:
orally administering to said subject a chimeric molecule comprising (a) an antibody, or fragment thereof, that specifically binds the aminopeptidase N (APN) receptor on mucosal intestinal epithelial cells, conjugated to (b) a heterologous antigen or therapeutic molecule, wherein said heterologous antigen or therapeutic molecule is delivered across the intestinal mucosal barrier by clathrin-mediated transcytosis.