Mammalian receptors as targets for antibody and active vaccination therapy against mold infections

Abstract

The present invention provides therapeutic compositions and methods for treating and preventing fungal disease or conditions including mucormycosis. The therapeutic methods and compositions of the invention include antibody, antibody fragments, siRNA and vaccine compositions having or directed against a GRP78 polypeptide or an antigenic fragment of the polypeptide.

What is claimed is: 
     
         1 . A method of preventing or treating mucormycosis, comprising administering a composition to a human subject having mucormycosis, wherein the composition comprises a therapeutically effective amount of an antibody or antibody fragment thereof that specifically binds to human glucose-regulated protein, 78kD, (GRP78) polypeptide or an antigenic fragment thereof, wherein said mucormycosis is caused by a fungus of the order Mucorales. 
     
     
         2 . The method of  claim 1 , wherein the antibody or fragment thereof blocks or abrogates endocytosis of the fungus by a human endothelial cell line that expresses the GRP78. 
     
     
         3 . The method of  claim 1 , wherein the fungus is of the family Mucoraceae. 
     
     
         4 . The method of  claim 3 , wherein the fungus is selected from the genus  Rhizopus, Mucor , and  Cunninghamella.    
     
     
         5 . The method of  claim 4 , wherein the fungus is a  Mucor  species. 
     
     
         6 . The method of  claim 4 , wherein the fungus is a  Cunninghamella  species. 
     
     
         7 . The method of  claim 3 , wherein said fungus is selected from the fungi species of  Rhizopus oryzae, Rhizopus microsporus, Rhizopus microsporus  var.  rhizopodiformis, Absidia corymbifera, Apophysomyces elegans, Cunninghamella bertholletiae , and  Rhizomucor pusillus.    
     
     
         8 . The method of  claim 1 , wherein said mucormycosis is selected from rhinocerebral mucormycosis, pulmonary mucormycosis, gastrointestinal mucormycosis, disseminated mucormycosis, bone mucormycosis, mediastinum mucormycosis, trachea mucormycosis, kidney mucormycosis, peritoneum mucormycosis, superior vena cava mucormycosis and external otitis mucormycosis. 
     
     
         9 . The method of  claim 1 , wherein the human subject is immunocompromised. 
     
     
         10 . The method of  claim 1 , wherein the human subject is suffering from diabetes mellitus. 
     
     
         11 . The method of  claim 1 , wherein the human subject is suffering from diabetic ketoacidosis. 
     
     
         12 . The method of  claim 1 , wherein the human subject is suffering from trauma. 
     
     
         13 . The method of  claim 1 , wherein the antibody is a monoclonal antibody, or the antibody fragment is a fragment of said monoclonal antibody. 
     
     
         14 . The method of  claim 1 , wherein the antibody is a humanized monoclonal antibody, or the antibody fragment is a fragment of the humanized monoclonal antibody.