Bvh-a2 and bvh-a3 antigens of group b streptococcus

Abstract

Group B Streptococcus polypeptides and polynucleotides encoding them are disclosed. Said polypeptides may be useful for the prophylaxis, diagnostic and/or therapy of streptococcal infection in mammals. Also disclosed are recombinant methods of producing the polypeptide antigens as well as diagnostic assays for detecting streptococcal infections, particularly GBS.

1 . An isolated polynucleotide comprising a polynucleotide chosen from;
 (a) a polynucleotide encoding a polypeptide having at least 70% identity to a second polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (b) a polynucleotide encoding a polypeptide having at least 95% identity to a second polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (c) a polynucleotide encoding a polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (d) a polynucleotide encoding a polypeptide which is able to raise antibodies having binding specificity for a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (e) a polynucleotide encoding an epitope bearing portion of a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (f) a polynucleotide comprising a nucleotide sequence chosen from SEQ ID NOS: 1, 2, 5 and 6 or fragments or analogs thereof; and   (g) a polynucleotide complementary to the polynucleotide of (a), (b), (c), (d), (e) or (f).   
     
     
         2 . An isolated polynucleotide comprising a polynucleotide chosen from;
 (a) a polynucleotide encoding a polypeptide having at least 70% identity to a second polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8;   (b) a polynucleotide encoding a polypeptide having at least 95% identity to a second polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8;   (c) a polynucleotide encoding a polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8;   (d) a polynucleotide encoding a polypeptide which is able to raise antibodies having binding specificity for a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8;   (e) a polynucleotide encoding an epitope bearing portion of a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8;   (f) a polynucleotide comprising a nucleotide sequence chosen from SEQ ID NOS: 1, 2, 5 and 6; and   (g) a polynucleotide complementary to the polynucleotide of (a), (b), (c), (d), (e), or (f).   
     
     
         3 . The polynucleotide of  claim 1 , wherein said polynucleotide is DNA. 
     
     
         4 . The polynucleotide of  claim 2 , wherein said polynucleotide is DNA. 
     
     
         5 . The polynucleotide of  claim 1 , wherein said polynucleotide is RNA. 
     
     
         6 . The polynucleotide of  claim 2 , wherein said polynucleotide is RNA. 
     
     
         7 . The polynucleotide of  claim 1  that hybridizes under stringent conditions to either
 (a) a polynucleotide encoding a polypeptide or   (b) the complement of a polynucleotide encoding a polypeptide;   
       wherein said polypeptide comprises SEQ ID NO: 3, 4, 7 and 8 or fragments or analogs thereof. 
     
     
         8 . The polynucleotide of  claim 2  that hybridizes under stringent conditions to either
 (a) a polynucleotide encoding a polypeptide or   (b) the complement of a polynucleotide encoding a polypeptide;   
       wherein said polypeptide comprises SEQ ID NO: 3, 4, 7 or 8. 
     
     
         9 . The polynucleotide of  claim 1  that hybridizes under stringent conditions to either
 (a) a polynucleotide encoding a polypeptide or   (b) the complement of a polynucleotide encoding a polypeptide;   
       wherein said polypeptide comprises at least 10 contiguous amino acid residues from a polypeptide comprising SEQ ID NO: 3, 4, 7 and 8 or fragments or analogs thereof. 
     
     
         10 . The polynucleotide of  claim 2  that hybridizes under stringent conditions to either
 (a) a polynucleotide encoding a polypeptide or   (b) the complement of a polynucleotide encoding a polypeptide;   
       wherein said polypeptide comprises at least 10 contiguous amino acid residues from a polypeptide comprising SEQ ID NO: 3, 4, 7 or 8. 
     
     
         11 . A vector comprising the polynucleotide of  claim 1 , wherein said polynucleotide is operably linked to an expression control region. 
     
     
         12 . A vector comprising the polynucleotide of  claim 2 , wherein said polynucleotide is operably linked to an expression control region. 
     
     
         13 . A host cell transfected with the vector of  claim 11 . 
     
     
         14 . A host cell transfected with the vector of  claim 12 . 
     
     
         15 . A process for producing a polypeptide comprising culturing the host cell according to  claim 13  under conditions suitable for expression of said polypeptide. 
     
     
         16 . A process for producing a polypeptide comprising culturing the host cell according to  claim 14  under condition suitable for expression of said polypeptide. 
     
     
         17 . An isolated polypeptide comprising a polypeptide chosen from:
 (a) a polypeptide having at least 70% identity to a second polypeptide having an amino acid sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (b) a polypeptide having at least 95% identity to a second polypeptide having an amino acid sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (c) a polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (d) a polypeptide which is able to raise antibodies having binding specificity for a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (e) an epitope bearing portion of a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof;   (f) the polypeptide of (a), (b), (c), (d) or (e) wherein the N-terminal Met residue is deleted; and   (g) the polypeptide of (a), (b), (c), (d) or (e) wherein the secretory amino acid sequence is deleted.   
     
     
         18 . An isolated polypeptide comprising a polypeptide chosen from:
 (a) a polypeptide having at least 70% identity to a second polypeptide having an amino acid sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8;   (b) a polypeptide having at least 95% identity to a second polypeptide having an amino acid sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8;   (c) a polypeptide comprising a sequence chosen from: SEQ ID NOS: 3, 4, 7 and 8;   (d) a polypeptide which is able to raise antibodies having binding specificity for a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8;   (e) an epitope bearing portion of a polypeptide having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8;   (f) the polypeptide of (a), (b), (c), (d) or (e) wherein the N-terminal Met residue is deleted; and   (g) the polypeptide of (a), (b), (c), (d) or (e) wherein the secretory amino acid sequence is deleted.   
     
     
         19 . A chimeric polypeptide comprising two or more polypeptides having a sequence chosen from SEQ ID NOS: 3, 4, 7 and 8 or fragments or analogs thereof; provided that the polypeptides are linked as to form a chimeric polypeptide. 
     
     
         20 . (canceled) 
     
     
         21 . A pharmaceutical composition comprising the polypeptide according to any one of  claims 17  to  19  and a pharmaceutically acceptable carrier, diluent or adjuvant. 
     
     
         22 . A method for prophylactic or therapeutic treatment of group B  Streptococcus  (GBS) bacterial infection in an individual susceptible to GBS infection comprising administering to said individual a therapeutic or prophylactic amount of the composition according to  claim 21 . 
     
     
         23 . A method according to  claim 22  wherein the individual is a neonate or an infant. 
     
     
         24 . A method according to  claim 23  wherein said infection causes sepsis, meningitis, pneumonia, cellulitis, osteomyelitis, septic arthritis, endocarditis or epiglottis. 
     
     
         25 . A method according to  claim 22  wherein the individual is a pregnant woman. 
     
     
         26 . A method according to  claim 25  wherein said infection causes mild urinary tract infection, sepsis, meningitis, osteomyelitis, endocarditis, amniotis, endometritis, postcesarean wound infection, postepisiotomy, wound infection, cellulitis, or fasciitis. 
     
     
         27 . A method according to  claim 22  wherein the individual is a non-pregnant adult. 
     
     
         28 . A method according to  claim 27  wherein said infection causes primary bacteremia, skin of soft tissue infection, pneumonia, urosepsis, endocarditis, peritonitis, meningitis or empyema. 
     
     
         29 . A method according to  claim 22  wherein the individual is a cow. 
     
     
         30 . A method according to  claim 29  wherein said infection causes mastitis. 
     
     
         31 . A method for diagnostic of group B  Streptococcus  (GBS) bacterial infection in an individual susceptible to GBS infection comprising:
 a. obtaining a biological sample from an individual;   b. incubating an antibody or antigen-binding fragment thereof reactive with the polypeptide of  claim 17  with the biological sample to form a mixture, and   c. detecting specifically bound antibody or bound antigen-binding fragment in the mixture which indicates the presence of GBS.   
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . Kit comprising the polypeptide according to any one of  claims 17  to  19  for detection or diagnosis of GBS infection.