Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia

Abstract

The present invention concerns the use of an inhibitor of an interaction between type IV pilus-associated protein and CD147 for preventing or treating meningoccal bacteraemia and/or infection. The present invention also relates to the combined use of such inhibitor and of an anti-bacterial compound, such as one used to prevent or treat a meningococcal infection. The invention also relates to a method for the prevention and/or treatment of meningococcal bacteraemia and/or infection, and to a method for screening inhibitors of the interaction between type IV pilus-associated protein and CD147.

What is claimed is: 
     
         1 . A method for preventing or treating a meningococcal bacteremia and/or infection in an individual in need thereof, comprising administering a therapeutically effective amount of an immunogenic PilV polypeptide comprising SEQ ID NO: 32, or a fragment thereof, or SEQ ID NO: 34, or a fragment thereof, capable of raising in the individual an immune response with antibodies that prevent the interaction between said type IV pilus-associated protein and the CD147 receptor. 
     
     
         2 . The method according to  claim 1 , wherein the immunogenic PilV polypeptide comprises or consists of a) SEQ ID NO: 32, or b) a fragment of at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 consecutive amino acids of the sequence SEQ ID NO: 32, or c) a sequence that is at least 80, 85 or 90% identical to the sequence of (a) or (b). 
     
     
         3 . The method according to  claim 1 , wherein the immunogenic PilV polypeptide comprises or consists of a) SEQ ID NO: 32, or b) a fragment of at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 consecutive amino acids of the sequence SEQ ID NO: 32, or c) a sequence that is at least, 95 or 99% identical to the sequence of (a) or (b). 
     
     
         4 . The method according to  claim 1 , wherein the immunogenic PilV fragment comprises or consists of a) SEQ ID NO: 34, or b) a fragment of at least 10, 15, 20, 25 consecutive amino acids of the sequence SEQ ID NO: 34, or c) a sequence that is at least 80, 85, 90% identical to the sequence of (a) or (b). 
     
     
         5 . The method according to  claim 1 , wherein the immunogenic PilV fragment comprises or consists of a) SEQ ID NO: 34, or b) a fragment of at least 10, 15, 20, 25 consecutive amino acids of the sequence SEQ ID NO: 34, or c) a sequence that is at least 95 or 99% identical to the sequence of (a) or (b). 
     
     
         6 . The method according to  claim 1 , further comprising administering at least one anti-bacterial compound, either sequentially or simultaneously. 
     
     
         7 . The method according to  claim 6 , wherein said anti-bacterial compound is selected from the group consisting of meningococcal PilE, PilV, PilX, PilC, ComP, fHbp, PorA, NHBA, NadA, MafA, NspA, HmbR, TbpB, and AusP, or an immunogenic fragment thereof. 
     
     
         8 . The method according to  claim 6 , wherein said anti-bacterial compound comprises or consists of PilE or an immunogenic fragment thereof. 
     
     
         9 . The method according to  claim 1 , wherein said immunogenic PilV polypeptide is formulated in a pharmaceutically acceptable composition.