Meningococcus adhesins nada, app and orf 40

Abstract

NadA, App and ORF40 function as adhesins in N. meningitidis . Adhesion can be modulated by targeting these three proteins. NadA allelic variants are disclosed. Autoproteolytic cleavage of App is disclosed, as is removal of the activity by mutagenesis. App is processed and secreted into culture medium when expressed in E. coli . Mature App proteins are disclosed. Knockout mutants are disclosed. Vesicles from non-Neisserial hosts with heterologous adhesin expression are disclosed.

1 . An isolated antibody that specifically binds to NMB1994, wherein NMB1994 comprises residues 24-343 of SEQ ID NO:2, or residues 24-350 of SEQ ID NO:3. 
     
     
         2 . The antibody of  claim 1 , wherein said antibody is a polyclonal antibody. 
     
     
         3 . The antibody of  claim 1 , wherein said antibody is a monoclonal antibody. 
     
     
         4 . The antibody of  claim 1 , wherein said antibody specifically binds to said NMB1994 comprising residues 24-343 of SEQ ID NO:2. 
     
     
         5 . The antibody of  claim 1 , wherein said antibody specifically binds to said NMB1994 comprising residues 24-350 of SEQ ID NO:3. 
     
     
         6 . The antibody of  claim 1 , wherein said antibody is able to bind to a bacterium of a  Neisseria meningitidis  strain that expresses NadA. 
     
     
         7 . The antibody of  claim 1 , wherein said antibody is able to induce complement-mediated killing of a  Neisseria meningitidis  strain that expresses NadA. 
     
     
         8 . The antibody of  claim 7 , wherein said strain is selected from the group consisting of 2996, C11, F6124 and MC58. 
     
     
         9 . The antibody of  claim 1 , wherein said antibody is able to reduce bacteremia in a subject exposed to a  Neisseria meningitidis  strain that expresses NadA. 
     
     
         10 . A method, comprising:
 administering an isolated antibody that specifically binds to NMB1994 to a subject,   wherein NMB1994 comprises residues 24-343 of SEQ ID NO:2, or residues 24-350 of SEQ ID NO:3.   
     
     
         11 . The method of  claim 10 , wherein said subject has been exposed to a  Neisseria meningitidis  strain that expresses NadA. 
     
     
         12 . The method of  claim 11 , wherein said administering reduces bacteremia. 
     
     
         13 . The method of  claim 10 , wherein said antibody specifically binds to said NMB1994 comprising residues 24-343 of SEQ ID NO:2. 
     
     
         14 . The method of  claim 10 , wherein said antibody specifically binds to said NMB1994 comprising residues 24-350 of SEQ ID NO:3. 
     
     
         15 . A method, comprising:
 contacting a bacterium of a  Neisseria meningitidis  strain that expresses NadA with an isolated antibody that specifically binds to NMB1994,   wherein NMB1994 comprises residues 24-343 of SEQ ID NO:2, or residues 24-350 of SEQ ID NO:3.   
     
     
         16 . The method of  claim 15 , wherein said antibody binds to said bacterium. 
     
     
         17 . The method of  claim 16 , wherein the ability of said bacterium to bind to an epithelial cell is blocked when bound to said antibody 
     
     
         18 . A method for preventing the attachment of a  Neisseria meningitidis  cell to an epithelial cell through NMB1994 mediated adhesion in a human subject by administering to the human subject an antibody that specifically binds to NMB1994, wherein NMB1994 comprises residues 24-343 of SEQ ID NO:2 or residues 24-350 of SEQ ID NO:3, and wherein the antibody inhibits NMB1994's ability to bind to the epithelial cell. 
     
     
         19 . The method of  claim 18 , wherein NMB1994 comprises residues 24-343 of SEQ ID NO:2. 
     
     
         20 . The method of  claim 18 , wherein NMB1994 comprises residues 24-350 of SEQ ID NO:3.