Immunotherapy and diagnosis of mucormycosis using coth

Abstract

The invention provided Mucorales CotH antibodies, polypeptides, encoding nucleic acid molecules, and uses thereof. The Mucorales CotH antibodies, polypeptides and encoding nucleic acids disclosed herein can be advantageously used to diagnose, treat or prevent fungal conditions, in particular mucormycosis.

What is claimed is: 
     
         1 . An isolated, non-naturally occurring anti-Mucorales CotH antibody, or binding fragment thereof, that (a) specifically binds a peptide having at least 87% sequence identity to amino acids 1 to 15 of SEQ ID NO: 39 or a peptide having at least 65% sequence identify to amino acids 1 to 17 of SEQ ID NO: 40, and (b) specifically binds to a CotH polypeptide on a fungus of order Mucorales. 
     
     
         2 . The antibody of  claim 1 , wherein the peptide sequence has a least 87% sequence identity to the amino acid sequence of SEQ ID NO: 39 or SEQ ID NO: 40. 
     
     
         3 . The antibody of  claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 39. 
     
     
         4 . The antibody of  claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 40. 
     
     
         5 . The antibody of  claim 1 , wherein the antibody specifically binds to the amino acid sequence of SEQ ID NO: 39. 
     
     
         6 . The antibody of  claim 1 , wherein the antibody specifically binds to the amino acid sequence of SEQ ID NO: 40. 
     
     
         7 . The antibody of  claim 1 , wherein the fungus is a pathogenic fungus that can cause mucormycosis in a human. 
     
     
         8 . The antibody of  claim 7 , wherein the pathogenic fungus belongs to the family Mucoraceae. 
     
     
         9 . The antibody of  claim 8 , wherein the pathogenic fungus belongs to genus  Rhizopus, Rhizomucor, Lichtheimia, Apophysomyces  or  Mucor.    
     
     
         10 . The antibody of  claim 9 , wherein the pathogenic fungus belongs to the genus  Lichtheimia  or  Mucor.    
     
     
         11 . The antibody of  claim 7 , wherein the pathogenic fungus is a species selected from  Lechtheimia corymbifera, Cunninghamella bertholletia, Rhizopus microspores, Mucor racemosus, Mucor circinelloides, Rhizomucor variabilis, Apophysomyces elegans , and  Apophysomyces trapeziformis.    
     
     
         12 . The antibody of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         13 . The antibody of  claim 12 , wherein the monoclonal antibody is a humanized antibody. 
     
     
         14 . The antibody of  claim 12 , wherein the monoclonal antibody is a chimeric antibody. 
     
     
         15 . The antibody of  claim 1 , wherein the binding fragment is a single chain antibody. 
     
     
         16 . The antibody of  claim 1 , wherein the antibody comprises a detectable marker. 
     
     
         17 . The antibody of  claim 1 , wherein the antibody abrogates endocytosis of the fungus by a mammalian endothelial cell. 
     
     
         18 . An isolated anti-Mucorales CotH antibody, or binding fragment thereof, that (a) specifically binds to a peptide having at least 87% sequence identity to amino acids 1 to 15 of SEQ ID NO: 39 or amino acids 1 to 17 of SEQ ID NO: 40, (b) specifically binds to a CotH polypeptide on a cell surface of a fungus of genus  Rhizopus, Rhizomucor, Lichtheimia, Mucor  or  Cunninghamella , wherein the CotH polypeptide on said cell surface comprises the peptide, and (c) abrogates endocytosis of the fungus by a mammalian endothelial cell, wherein (i) the antibody is a humanized antibody, a chimeric antibody, a CDR-grafted antibody, or a bifunctional antibody, or (ii) the binding fragment is selected from a single chain antibody, Fab, F(ab′)2, Fd and an Fv fragment. 
     
     
         19 . The antibody of  claim 1 , wherein the non-naturally occurring antibody, or binding fragment thereof, is selected from a humanized antibody, chimeric antibody, CDR-grafted antibody, a bifunctional antibody, a single chain antibody, Fab, F(ab′)2, Fd and an Fv fragment. 
     
     
         20 . The antibody of  claim 1 , wherein the fungus of order Mucorales is a pathogenic fungus of family Cunninghamellaceae.