Compounds and methods for diagnosis and immunotherapy of tuberculosis

Abstract

Compounds and methods for diagnosing tuberculosis or for inducing protective immunity against tuberculosis are disclosed. The compounds provided include polypeptides that contain at least one immunogenic portion of one or more Mycobacterium proteins and DNA molecules encoding such polypeptides. Diagnostic kits containing such polypeptides or DNA sequences and a suitable detection reagent may be used for the detection of Mycobacterium infection in patients and biological samples. Antibodies directed against such polypeptides are also provided. In addition, such compounds may be formulated into vaccines and/or pharmaceutical compositions for immunization against Mycobacterium infection.

1 . An isolated nucleic acid comprising a nucleotide sequence encoding a polypeptide sequence comprising the amino acid sequence of SEQ ID NO: 138. 
     
     
         2 . The isolated nucleic acid of  claim 1 , consisting of the nucleic acid sequence encoding a polypeptide sequence comprising the amino acid sequence of SEQ ID NO: 138. 
     
     
         3 . An isolated nucleic acid comprising a nucleotide sequence encoding a polypeptide sequence having at least 90% identity to the sequence of SEQ ID NO: 138. 
     
     
         4 . The isolated nucleic acid sequence of  claim 3  comprising a nucleotide sequence encoding a polypeptide sequence having at least 95% identity to the sequence of SEQ ID NO: 138. 
     
     
         5 . A composition comprising a physiologically acceptable carrier and the nucleic acid of  claim 1 . 
     
     
         6 . An isolated nucleic acid comprising a nucleotide sequence encoding a polypeptide sequence comprising an immunogenic fragment of a polypeptide consisting of the amino acid sequence of SEQ ID NO: 138, wherein the fragment is at least 9 amino acids in length. 
     
     
         7 . A pharmaceutical composition comprising the nucleic acid of  claim 6  and a physiologically acceptable carrier. 
     
     
         8 . A composition comprising an isolated nucleic acid comprising a nucleotide sequence encoding a polypeptide sequence comprising an immunogenic fragment of a polypeptide consisting of the amino acid sequence of SEQ ID NO: 138, wherein the fragment is at least 9 amino acids in length, and a pharmaceutically acceptable carrier. 
     
     
         9 . A nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising an isolated polypeptide comprising an immunogenic fragment of the polypeptide consisting of the amino acid sequence of SEQ ID NO: 138, wherein the fragment is at least 9 amino acids in length, and a second polypeptide. 
     
     
         10 . The fusion protein of  claim 9 , wherein the second polypeptide is a  Mycobacterium tuberculosis  antigen. 
     
     
         11 . The composition of  claim 16 , wherein the non-specific immune response enhancer is an adjuvant. 
     
     
         12 . A composition comprising: a nucleic acid encoding a fusion protein comprising an isolated polypeptide comprising an immunogenic fragment of the polypeptide consisting of the amino acid sequence of SEQ ID NO:138, wherein the fragment is at least 9 amino acids in length and a second polypeptide; and a pharmaceutically acceptable carrier. 
     
     
         13 . An isolated nucleic acid comprising the sequence of SEQ ID NO: 137. 
     
     
         14 . The isolated nucleic acid of  claim 13  consisting of the sequence of SEQ ID NO: 137. 
     
     
         15 . The isolated nucleic acid sequence of  claim 13  having at least 85% identity to the sequence of SEQ ID NO: 137. 
     
     
         16 . The isolated nucleic acid sequence of  claim 15  having at least 90% identity to the sequence of SEQ ID NO: 137. 
     
     
         17 . The isolated nucleic acid sequence of  claim 16  having at least 95% identity to the sequence of SEQ ID NO: 137.