Pharmaceutical compositions and methods to vaccinate against candidiasis

Abstract

A Candida albicans bloodstream infections cause significant morbidity and mortality in hospitalized patients. Filament formation and adherence to host cells are critical virulence factors of C. albicans . Multiple filamentation regulatory pathways have been discovered, however the downstream effectors of these regulatory pathways remain unknown. The cell surface proteins in the ALS group are downstream effectors of the filamentation regulatory pathway. Particularly, Als1p mediates adherence to endothelial cells in vitro and is required for virulence. The blocking of adherence by the organism is described resulting from the use of a composition and method disclosed herein. Specifically, a pharmaceutical composition comprised of a gene, gene product, or specific antibody to the ALS gene family is administered as a vaccine to generate an immune response capable of blocking adherence of the organism.

1 .- 21 . (canceled) 
     
     
         22 . A monoclonal antibody against a  Candida albicans  agglutinin-like sequence 3 (ALS3) protein that specifically binds an epitope within amino acids 17 to 432 of SEQ ID NO: 12. 
     
     
         23 . The monoclonal antibody of  claim 22 , wherein the monoclonal antibody inhibits filamentation of  Candida albicans.    
     
     
         24 . The monoclonal antibody of  claim 22 , wherein the monoclonal antibody is an IgG isotype. 
     
     
         25 . A hybridoma cell line that produces the monoclonal antibody of  claim 22 . 
     
     
         26 . A pharmaceutical composition comprising the monoclonal antibody of  claim 22  and a pharmaceutically acceptable carrier. 
     
     
         27 . The pharmaceutical composition of  claim 26  further comprising polyclonal immunoglobulins against a  Candida albicans  ALS3 protein that specifically binds an epitope within amino acids 17 to 432 of SEQ ID NO: 12. 
     
     
         28 . A method for treating candidiasis comprising administering the composition of  claim 26  to a subject in need thereof. 
     
     
         29 . The method of  claim 28 , wherein the composition comprises monoclonal antibodies. 
     
     
         30 . The method of  claim 29 , wherein the monoclonal antibodies are an IgG isotype. 
     
     
         31 . The method of  claim 28 , wherein the composition comprises polyclonal antibodies against a  Candida albicans  ALS3 protein that specifically binds an epitope within amino acids 17 to 432 of SEQ ID NO: 12. 
     
     
         32 . The method of  claim 28 , wherein the subject is a human. 
     
     
         33 . The method of  claim 28 , wherein the composition is administered to the subject by intramuscular, intraperitoneal, or sub-cutaneous injection.