Transferrin-binding proteins from n.gonorrhoeae and n. meningitidis

Abstract

Iron-regulated, outer membrane proteins found in Neisseria gonorrhoeae and Neisseria meningitidis are important in transferrin receptor function. The proteins, which are isolatable by means of a transferrin affinity column, bind specifically to antisera raised against an iron-regulated outer membrane protein having a molecular weight of approximately 100 kD found in Neisseria gonorrhoeae.

1 . An iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (a) detergent;    (b) nitrocellulose/cellulose acetate paper; and    (c) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis ; and    wherein the protein is isolatable by means of a transferrin affinity column; and    wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD; and    wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis ; and functional analogs of such proteins.    
     
     
         2 . The protein of  claim 1  wherein the protein is found in  Neisseria gonorrhoeae  and has a molecular weight of 100 kD.  
     
     
         3 . The protein of  claim 1  wherein the protein is found in  Neisseria meningitidis  and has a molecular weight of 95 kD.  
     
     
         4 . The protein of  claim 1  wherein the protein is a  Neisseria gonorrhoeae  or  Neisseria meningitidis  transferrin receptor.  
     
     
         5 . The protein of  claim 1  wherein the protein has a detectable label.  
     
     
         6 . Isolated antibodies raised against an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (a) detergent;    (b) nitrocellulose/cellulose acetate paper; and    (c) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis ; and    wherein the protein is isolatable by means of a transferrin affinity column; and    wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD; and    wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis ; and functional analogs of such proteins.    
     
     
         7 . The antibodies of  claim 6  wherein the antibodies are suitable for detecting the presence of  Neisseria gonorrhoeae  or  Neisseria meningitidis  in a sample.  
     
     
         8 . The antibodies of  claim 6  wherein the antibodies are suitable for treating a mammal infected with  N. gonorrhoeae  or  N. meningitidis.    
     
     
         9 . The antibodies of  claim 6  wherein binding of the antibodies to the protein inhibits growth of  Neisseria gonorrhoeae  or  Neisseria meningitidis.    
     
     
         10 . The antibodies of  claim 6  wherein the binding of the antibodies blocks transferrin receptor function of the protein.  
     
     
         11 . The antibodies of  claim 6  wherein the antibodies are monoclonal.  
     
     
         12 . A vaccine composition comprising an effective amount of an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (a) detergent;    (b) nitrocellulose/cellulose acetate paper; and    (c) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis;      wherein the protein is isolatable by means of a transferrin affinity column;    wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD;    wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis , and functional analogs of such proteins; and    a pharmaceutically acceptable carrier.    
     
     
         13 . The vaccine of  claim 12  wherein the protein is found in  Neisseria gonorrhoeae  and has a molecular weight of 100 kD.  
     
     
         14 . The vaccine of  claim 12  wherein the protein is found in  Neisseria meningitidis  and has a molecular weight of 95 kD.  
     
     
         15 . A method of immunizing a mammal against diseases caused by  N. gonorrhoeae  or  N. meningitidis  comprising the step of administering to the host a vaccine composition comprising an effective amount of an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (a) detergent;    (b) nitrocellulose/cellulose acetate paper; and    (c) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis;      wherein the protein is isolatable by means of a transferrin affinity column;    wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD;    wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis , and functional analogs of such proteins; and    a pharmaceutically acceptable carrier.    
     
     
         16 . A method of treating a mammal suffering from diseases caused by  N. gonorrhoeae  or  N. meningitidis , the method comprising administering to the mammal an effective amount of isolated antibodies raised against an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (a) detergent;    (b) nitrocellulose/cellulose acetate paper; and    (c) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis;      wherein the protein is isolatable by means of a transferrin affinity column;    wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD; and    wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis ; and functional analogs of such proteins.    
     
     
         17 . A nucleotide sequence encoding an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (a) detergent;    (b) nitrocellulose/cellulose acetate paper; and    (c) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis;      wherein the protein is isolatable by means of a transferrin affinity column;    wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD; and    wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis ; and functional analogs of such proteins and functional derivatives of such proteins.    
     
     
         18 . A method for detecting the presence of antibodies specific for  N. gonorrhoeae  and  N. meningitidis  in a sample, the method comprising the steps of: 
 (a) incubating a protein according to  claim 1  with a sample suspected of containing antibodies to an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (1) detergent;  
 (2) nitrocellulose/cellulose acetate paper; and  
 (3) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis;    
 wherein the protein is isolatable by means of a transferrin affinity column;  
 wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD; and  
 wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis ; and functional analogs of such proteins;  
   (b) labeling the protein either before, during, or after the incubation of step (a); and    (c) detecting the labeled protein bound to an antibody in the sample.    
     
     
         19 . A method for detecting the presence of  N. gonorrhoeae  or  N. meningitidis  in a sample comprising the steps of: 
 (a) incubating a sample suspected of containing  N. gonorrhoeae  or  N. meningitidis  with an antibody raised against an iron-regulated protein found in  Neisseria gonorrhoeae  or  Neisseria meningitidis  outer membranes, wherein the protein is substantially free of: 
 (1) detergent;  
 (2) nitrocellulose/cellulose acetate paper; and  
 (3) other iron-regulated proteins from  Neisseria gonorrhoeae  and  Neisseria meningitidis;    
 wherein the protein is isolatable by means of a transferrin affinity column;  
 wherein the protein binds specifically to antisera raised against an iron-regulated outer membrane protein found in  Neisseria gonorrhoeae  having a molecular weight of approximately 100 kD; and  
 wherein the protein is important in transferrin receptor function in  Neisseria gonorrhoeae  or  Neisseria meningitidis ; and functional analogs of such proteins;  
   (b) labeling the antibody either before, during, or after the incubation of step (a); and    (c) detecting the presence of antibody bound to the protein.