Chlamydia antigens and corresponding DNA fragments and uses thereof

Abstract

The present invention provides purified and isolated polynucleotide molecules that encode Chlamydia polypeptides which can be used in methods to prevent, treat, and diagnose Chlamydia infection. In one form of the invention, the polynucleotide molecules are selected from DNA that encode polypeptides CPN100686 RY-54 (SEQ ID Nos: 1 and 14), CPN100696 RY-55 (SEQ ID Nos: 2 and 15), CPN100709 RY-57 (SEQ ID Nos: 3 and 16), CPN100710 RY-58 (SEQ ID Nos: 4 and 17), CPN100711 RY-59 (SEQ ID Nos: 5 and 18), CPN100877 RY-61 (SEQ ID Nos: 6 and 19), CPN100325 RY-62 (SEQ ID Nos: 7 and 20), CPN100368 RY-63 (SEQ ID Nos: 8 and 21), CPN100624 RY-64 (SEQ ID Nos: 9 and 22), CPN100633 RY-65 (SEQ ID Nos: 10 and 23), CPN100985 RY-66 (SEQ ID Nos: 11 and 24), CPN100987 RY-67 (SEQ ID Nos: 12 and 25), CPN100988 RY-68 (SEQ ID Nos: 13 and 26).

1 . A nucleic acid molecule comprising a nucleic acid sequence which encodes a polypeptide selected from any of: 
 (a) SEQ ID Nos: 14 to 26;    (b) an immunogenic fragment comprising at least 12 consecutive amino acids from a polypeptide of (a); and    (c) a polypeptide of (a) or (b) which has been modified to improve its immunogenicity, wherein said modified polypeptide is at least 75% identical in amino acid sequence to the corresponding polypeptide of (a) or (b).    
     
     
         2 . A nucleic acid molecule comprising a nucleic acid sequence selected from any of: 
 (a) SEQ ID Nos: 1 to 13;    (b) a sequence which encodes a polypeptide encoded by any one of SEQ ID Nos: 1 to 13;    (c) a sequence comprising at least 38 consecutive nucleotides from any one of the nucleic acid sequences of (a) and (b); and    (d) a sequence which encodes a polypeptide which is at least 75% identical in amino acid sequence to any one of the polypeptides encoded by SEQ ID Nos: 1 to 13.    
     
     
         3 . A nucleic acid molecule comprising a nucleic acid sequence which is anti-sense to the nucleic acid molecule of  claim 1  or  2 .  
     
     
         4 . A nucleic acid molecule comprising a nucleic acid sequence which encodes a fusion protein, said fusion protein comprising a polypeptide encoded by a nucleic acid molecule according to  claim 1  and an additional polypeptide.  
     
     
         5 . The nucleic acid molecule of  claim 4  wherein the additional polypeptide is a heterologous signal peptide.  
     
     
         6 . The nucleic acid molecule of  claim 4  wherein the additional polypeptide has adjuvant activity.  
     
     
         7 . A nucleic acid molecule according to any one of  claims 1  to  6 , operatively linked to one or more expression control sequences.  
     
     
         8 . A vaccine comprising at least one first nucleic acid according to any one of claims  1 ,  2 , and  4  to  7  and a vaccine vector wherein each first nucleic acid is expressed as a polypeptide, the vaccine optionally comprising a second nucleic acid encoding an additional polypeptide which enhances the immune response to the polypeptide expressed by said first nucleic acid.  
     
     
         9 . The vaccine of  claim 8  wherein the second nucleic acid encodes an additional Chlamydia polypeptide.  
     
     
         10 . A pharmaceutical composition comprising a nucleic acid according to any one of  claims 1  to  7  and a pharmaceutically acceptable carrier.  
     
     
         11 . A pharmaceutical composition comprising a vaccine according to  claim 8  or  9  and a pharmaceutically acceptable carrier.  
     
     
         12 . A unicellular host transformed with the nucleic acid molecule of  claim 7 .  
     
     
         13 . A nucleic acid probe of 5 to 100 nucleotides which hybridizes under stringent conditions to any one of nucleic acid molecules of SEQ ID Nos: 1 to 13, or to a homolog or complementary or anti-sense sequence of said nucleic acid molecule.  
     
     
         14 . A primer of 10 to 40 nucleotides which hybridizes under stringent conditions to any one of nucleic acid molecules of SEQ ID Nos: 1 to 13, or to a homolog or complementary or anti-sense sequence of said nucleic acid molecule.  
     
     
         15 . A polypeptide encoded by a nucleic acid sequence according to any one of claims  1 ,  2  and  4  to  7 .  
     
     
         16 . A polypeptide comprising an amino acid sequence selected from any of: 
 (a) SEQ ID Nos: 14 to 26;    (b) an immunogenic fragment comprising at least 12 consecutive amino acids from a polypeptide of (a); and    (c) a polypeptide of (a) or (b) which has been modified to improve its immunogenicity, wherein said modified polypeptide is at least 75% identical in amino acid sequence to the corresponding polypeptide of (a) or (b).    
     
     
         17 . A fusion polypeptide comprising a polypeptide of  claim 15  or  16  and an additional polypeptide.  
     
     
         18 . The fusion polypeptide of  claim 17  wherein the additional polypeptide is a heterologous signal peptide.  
     
     
         19 . The fusion protein of  claim 17  wherein the additional polypeptide has adjuvant activity.  
     
     
         20 . A method for producing a polypeptide of  claim 15  or  16 , comprising the step of culturing a unicellular host according to  claim 12 .  
     
     
         21 . An antibody against the polypeptide of any one of  claims 15  to  19 .  
     
     
         22 . A vaccine comprising at least one first polypeptide according to any one of  claims 15  to  19  and a pharmaceutically acceptable carrier, optionally comprising a second polypeptide which enhances the immune response to the first polypeptide.  
     
     
         23 . The vaccine of  claim 22  wherein the second polypeptide comprises an additional Chlamydia polypeptide.  
     
     
         24 . A pharmaceutical composition comprising a polypeptide according to any one of  claims 15  to  19  and a pharmaceutically acceptable carrier.  
     
     
         25 . A pharmaceutical composition comprising a vaccine according to  claim 22  or  23  and a pharmaceutically acceptable carrier.  
     
     
         26 . A pharmaceutical composition comprising an antibody according to  claim 21  and a pharmaceutically acceptable carrier.  
     
     
         27 . A method for preventing or treating Chlamydia infection using: 
 (a) the nucleic acid of any one of  claims 1  to  7 ;    (b) the vaccine of any one of claims  8 ,  9 ,  22  and  23 ;    (c) the pharmaceutical composition of any one of claims  10 ,  11 ,  24  to  26 ;    (d) the polypeptide of any one of  claims 15  to  19 ; or    (e) the antibody of  claim 21 .    
     
     
         28 . A method of detecting Chlamydia infection comprising the step of assaying a body fluid of a mammal to be tested, with a component selected from any one of: 
 (a) the nucleic acid of any one of  claims 1  to  7 ;    (b) the polypeptide of any one of  claims 15  to  19 ; and    (c) the antibody of  claim 21 .    
     
     
         29 . A diagnostic kit comprising instructions for use and a component selected from any one of: 
 (a) the nucleic acid of any one of  claims 1  to  7 ;    (b) the polypeptide of any one of  claims 15  to  19 ; and    (c) the antibody of  claim 21 .    
     
     
         30 . A method for identifying a polypeptide of  claims 15  to  19  which induces an immune response effective to prevent or lessen the severity of Chlamydia infection in a mammal previously immunized with polypeptide, comprising the steps of: 
 (a) immunizing a mouse with the polypeptide; and  
 (b) inoculating the immunized mouse with Chlamydia;  
 wherein the polypeptide which prevents or lessens the severity of Chlamydia infection in the immunized mouse compared to a non-immunized control mouse is identified.