Antibodies to the propeptide of candida albicans and methods of use

Abstract

Antibodies and agents which can bind to the propeptide of the Int1p protein of yeast microorganisms such as Candida albicans are provided which can be useful in methods for treating or preventing infections arising from such microorganisms. Microorganisms expressing the Int1p protein, such as C. albicans and S. cerevisiae, can immunomodulate host cells which allows infections of these microorganisms to thrive and become virulent. The present invention provides peptide regions involved in the activation of the Int1p protein that can provide a method of disrupting said activation to treat or prevent infection by microorganisms expressing the int1p protein. In one preferred embodiment, an antibody or agent which can bind to the propeptide or other region of the Int1p protein from C. albicans is utilized in methods to prevent or treat infections caused by C. albicans or other microorganisms expressing the Int1p protein.

1 . A method of treating or preventing an infection by a microorganism expressing the Int1p protein comprising administering to a human or animal patient in need thereof an effective amount of an isolated antibody that binds to the propeptide of the Int1p protein of  Candida albicans  having the sequence consisting of the amino acid residues 1-263 of SEQ ID NO:1.  
     
     
         2 . The method according to  claim 1  wherein said antibody is capable of preventing the cleaving of the propeptide.  
     
     
         3 . The method according to  claim 1  wherein the microorganism is selected from the group consisting of  Candida albicans  and  Saccharomyces cerevisiae.    
     
     
         4 . The method according to  claim 1  wherein the antibody is raised against a portion of the propeptide of Int1p effective to generate an immune response.  
     
     
         5 . A method for treating patients exposed to  Candida albicans  in the presence of heparin, the method comprising: 
 administering an isolated antibody that binds to the propeptide of the Int1p protein of  Candida albicans  having the sequence consisting of the amino acid residues 1-263 of SEQ ID NO:1 to a human or animal patient in an amount effective to bind with the heparin and to reduce or eliminate the activation of the Int1p protein.    
     
     
         6 . An isolated antibody that binds to a peptide region selected from the group consisting of the Catalytic domain 1 at amino acids 435-639, the Catalytic domain 2 at amino acids 738-949, and the Processing domain motif at amino acids 1022-1236 of the amino acid sequence of SEQ ID NO: 1.  
     
     
         7 . The isolated antibody according to  claim 6  wherein said antibody is capable of preventing the cleaving of the propeptide.  
     
     
         8 . Isolated antisera containing the antibody according to  claim 6 .  
     
     
         9 . A method of treating or preventing an infection by a microorganism expressing the Int1p protein comprising administering an effective amount of the antibody according to  claim 6  to a human or animal patient in need thereof.  
     
     
         10 . A method of diagnosing an infection by a microorganism capable of expressing an Int1p protein comprising introducing the antibody according to  claim 6  into a sample suspected of having an infection by an Int1p-producing microorganism and determining the binding of said antibody to said sample.  
     
     
         11 . A diagnostic kit comprising the antibody according to  claim 6  and means for detecting binding by that antibody.  
     
     
         12 . An isolated peptide selected from the group consisting of the propeptide region at amino acids 1-263, the Catalytic domain 1 at amino acids 435-639, the Catalytic domain 2 at amino acids 738-949, and the Processing domain motif at amino acids 1022-1236 of the amino acid sequence of SEQ ID NO:1.  
     
     
         13 . A method of generating an antibody comprising introducing a peptide according to  claim 12  in a host capable of generating antibodies thereto.  
     
     
         14 . An isolated nucleic acid sequence coding for the peptide according to  claim 12 .  
     
     
         15 . A method of inducing an immunological response comprising administering to a patient the peptide according to  claim 12 .  
     
     
         16 . A vaccine comprising the peptide according to  claim 12  in an amount effective to generate an immunological response.  
     
     
         17 . A pharmaceutical composition comprising the peptide according to  claim 12  and a pharmaceutically acceptable vehicle, carrier or excipient.  
     
     
         18 . An isolated monoclonal antibody raised against the peptide of  claim 12 .  
     
     
         19 . A method according to  claim 10  wherein the microorganism is selected from the group consisting of  Candida albicans  and  Saccharomyces cerevisiae.    
     
     
         20 . A method of treating or preventing infections caused by microorganisms expressing the Int1p protein comprising administering an effective amount of an agent that inhibits Int1p activity.  
     
     
         21 . A method according to  claim 20  wherein the agent modulates a peptide region or motif from the Int1p protein which is involved in the pathway of activation for the Int1p protein.  
     
     
         22 . A method according to  claim 20  wherein the agent modulates a peptide selected from the group consisting of the propeptide region at amino acids 1-263, the Catalytic domain 1 at amino acids 435-639, the Catalytic domain 2 at amino acids 738-949, and the Processing domain motif at amino acids 1022-1236 of the amino acid sequence of SEQ ID NO: 1.  
     
     
         23 . A method according to  claim 20  wherein the microorganism is a yeast of the  Candida  species.  
     
     
         24 . A method according to  claim 20  wherein the microorganism is selected from the group consisting of  Candida albicans  and  Saccharomyces cerevisiae.