Neisseria meningitidis polypeptide, nucleic acid sequence and uses thereof

Abstract

The invention discloses the Neisseria meningitidis NMASP polypeptide, polypeptides derived therefrom (NMASP-derived polypeptides), nucleotide sequences encoding said polypeptides, and antibodies that specifically bind the NMASP polypeptide and/or NMASP-derived polypeptides. Also disclosed are prophylactic or therapeutic compositions, including immunogenic compositions, e.g., vaccines, comprising NMASP polypeptide and/or a NMASP-derived polypeptide. The invention additionally discloses methods of inducing a immune response to Neisseria meningitidis and Neisseria meningitidis NMASP polypeptide and an NMASP-derived polypeptide in animals.

What is claimed is:  
     
         1 . An isolated NMASP polypeptide, which is a polypeptide of  Neisseria meningitidis , and has a molecular weight of about 40 kD to about 55 kD as determined in SDS polyacrylamide gel electrophoresis.  
     
     
         2 . The NMASP polypeptide of  claim 1 , which has a molecular weight of about 44 TO 53 kD.  
     
     
         3 . The NMASP polypeptide of  claim 1 , wherein the  Neisseria meningitidis  is selected from the group consisting of Types A-L and W.  
     
     
         4 . The NMASP polypeptide of  claim 3 , which  Neisseria meningitidis  is Type A, Type B, Type C or Type W.  
     
     
         5 . The NMASP polypeptide of  claim 1 , comprising a sequence selected from the group consisting of SEQ ID NOs: 2, 11, or 12, a sequence substantially homologous thereto, and a fragment thereof.  
     
     
         6 . The NMASP polypeptide of  claim 1  or a peptide fragment thereof, which specifically binds an antibody that specifically binds to a protein having the sequence selected from the group consisting of SEQ ID NOs: 2, 11, or 12,.  
     
     
         7 . A peptide fragment of the NMASP polypeptide of  claim 1 .  
     
     
         8 . A peptide fragment of the NMASP polypeptide of  claim 5 .  
     
     
         9 . A peptide fragment of the NMASP polypeptide of  claim 6 .  
     
     
         10 . An isolated antibody that specifically binds the NMASP polypeptide of  claim 1  or a fragment thereof.  
     
     
         11 . An isolated antibody that specifically binds the NMASP polypeptide of  claim 5  or a fragment thereof.  
     
     
         12 . An isolated antibody that specifically binds the NMASP polypeptide of  claim 6  or a fragment thereof.  
     
     
         13 . The isolated antibody of  claim 10 ,  11 , or  12  which is a cytotoxic antibody that mediates complement killing of  Neisseria meningitidis    
     
     
         14 . An antigenic composition comprising the NMASP polypeptide of any of claims  1 ,  5 , or  6  and a pharmaceutically acceptable carrier or diluent.  
     
     
         15 . An antigenic composition comprising the peptide fragment of  claim 7 ,  8 , or  9  and a pharmaceutically acceptable carrier or diluent.  
     
     
         16 . The antigenic composition of  claim 14  additionally comprising one or more adjuvants or immunostimulatory compounds.  
     
     
         17 . The antigenic composition of  claim 15  additionally comprising one or more adjuvants or immunostimulatory compounds.  
     
     
         18 . The antigenic composition of  claim 16  further comprising one or more immunogens selected from the group consisting of lipids, lipooligosaccharides, proteins, attenuated organisms and inactivated whole cells.  
     
     
         19 . The antigenic composition of  claim 18 , wherein the lipid is a phospholipid.  
     
     
         20 . The antigenic composition of  claim 17  further comprising optionally one or more immunogens selected from the group consisting of lipids, lipooligosaccharides, proteins, attenuated organisms and inactivated whole cells.  
     
     
         21 . The antigenic composition of  claim 20 , wherein the lipid is a phospholipid.  
     
     
         22 . A vaccine composition comprising the NMASP polypeptide of any of claims  1 ,  5 , or  6  and a pharmaceutically acceptable carrier or diluent.  
     
     
         23 . A vaccine composition comprising the peptide fragment of  claim 7 ,  8 , or  9  and a pharmaceutically acceptable carrier or diluent.  
     
     
         24 . The vaccine of  claim 22  additionally comprising one or more adjuvants or immunostimulatory compounds.  
     
     
         25 . The vaccine of  claim 23  additionally comprising one or more adjuvants or immunostimulatory compounds.  
     
     
         26 . The vaccine of  claim 24  further comprising one or more immunogens selected from the group consisting of lipids, lipooligosaccharides, proteins, attenuated organisms and inactivated whole cells.  
     
     
         27 . The vaccine of  claim 26 , wherein the lipid is a phospholipid.  
     
     
         28 . The vaccine of  claim 25  further comprising one or more immunogens selected from the group consisting of lipids, lipooligosaccharides, proteins, attenuated organisms and inactivated whole cells.  
     
     
         29 . The vaccine of  claim 28 , wherein the lipid is a phospholipid.  
     
     
         30 . A pharmaceutical composition comprising the NMASP polypeptide of any of claims  1 ,  5  or  6  and a pharmaceutically acceptable carrier or diluent.  
     
     
         31 . A pharmaceutical composition comprising the peptide fragment of  claim 7 ,  8 , or  9  and a pharmaceutically acceptable carrier or diluent.  
     
     
         32 . The pharmaceutical composition of  claim 30  additionally comprising one or more adjuvants or immunostimulatory compounds.  
     
     
         33 . The pharmaceutical composition of  claim 31  additionally comprising one or more adjuvants or immunostimulatory compounds.  
     
     
         34 . The pharmaceutical composition of  claim 32  further comprising optionally one or more immunogens selected from the group consisting of lipids, lipooligosaccharides, proteins, attenuated organisms and inactivated whole cells.  
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the lipid is a phospholipid.  
     
     
         36 . The pharmaceutical composition of  claim 33  further comprising optionally one or more immunogens selected from the group consisting of lipids, lipooligosaccharides, proteins, attenuated organisms and inactivated whole cells.  
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the lipid is a phospholipid.  
     
     
         38 . A pharmaceutical composition comprising the antibodies of  claim 10 ,  11 ,  12  or  13 .  
     
     
         39 . An isolated DNA comprising a nucleotide sequence encoding the NMASP polypeptide of  claim 1 ,  5  or  6  or fragment thereof.  
     
     
         40 . An isolated DNA comprising a nucleotide sequence encoding the peptide of SEQ ID NOs: 2, 11 or 12, or fragment thereof.  
     
     
         41 . An isolated DNA having the sequence of SEQ ID NOs: 1, 10 or 13, or fragment thereof.  
     
     
         42 . An isolated DNA having the sequence of SEQ ID NOs: 3, 4, 8, 9, 14-15, 17-20, or the complement thereof.  
     
     
         43 . An isolated DNA encoding an NMASP polypeptide, which comprises a nucleotide sequence that hybridizes under high stringency conditions to the sequence of SEQ ID NOs: 1, 10 or 13 or the complement thereof.  
     
     
         44 . An isolated DNA which comprises a nucleotide sequence that hybridizes under high stringency conditions to the sequence of SEQ ID NOs: 1, 3, 4, 8, 9, 10, 13-15, 17-20, or the complement thereof.  
     
     
         45 . A pharmaceutical composition comprising the isolated DNA of any one of claims  39 ,  40 ,  41 ,  42 ,  43  or  44 .  
     
     
         46 . A method of producing an immune response in an animal comprising immunizing the animal with an effective amount of the NMASP polypeptide of any of claims  1 ,  5  or  6 .  
     
     
         47 . A method of producing an immune response in an animal comprising immunizing the animal with an effective amount of the peptide fragment of  claim 7 ,  8 , or  9 .  
     
     
         48 . Plasmid pNmAH116 obtainable from  E. coli  Top10 (pNmAH116), as deposited with the ATCC and assigned accession number 98839.  
     
     
         49 . A method for assaying for an agent that interacts with NMASP polypeptide comprising: 
 a. contacting a cell expressing NMASP polypeptide with an agent labeled with a detectable marker for a time sufficient to allow the agent to interact with the polypeptide;    b. washing the cells; and    c. detecting any marker associated with the cells, in which any cell associated marker indicates that the agent interacts with the NMASP polypeptide and wherein any agent that interacts with NMASP indicates that the agent is useful as a diagnostic, prophylactic or therapeutic agent against  Neisseria meningitidis  infection.    
     
     
         50 . An antagonist which inhibits the activity or expression of the NMASP polypeptide of  claim 5 .  
     
     
         51 . A method for identifying compounds which interact with and inhibit or activate an activity of the NMASP polypeptide of  claim 5  comprising: 
 contacting a composition comprising the polypeptide with the compound to be screened under conditions to permit interaction between the compound and the polypeptide to assess the interaction of a compound, such interaction being associated with a second component capable of providing a detectable signal in the presence or absence of a signal generated from the interaction of the compound with the polypeptide.