Tuberculosis nucleic acids, polypeptides and immunogenic compositions

Abstract

The present invention provides transcriptionally active Mtb polynucleotides, recombinant Mtb peptides and polypeptides, and immunogenic Mtb antigens. Immunogenic compositions are also provided that may be useful as recombinant, subunit and DNA vaccines. In addition the invention provides diagnostic kits for Mtb.

1 . An isolated polynucleotide encoding a Mtb polypeptide that is antigenic in a mammal, wherein the polynucleotide is selected from the group consisting of: (a) SEQ ID NOS: 46-64, 110-121; or (b) a fragment thereof, wherein the fragment encodes an antigenic peptide epitope. 
     
     
         2 . The isolated polynucleotide of  claim 1 , wherein said mammal is a rabbit, human or mouse. 
     
     
         3 . (canceled) 
     
     
         4 . The polynucleotide of  claim 1 , wherein said Mtb polypeptide reacts with polyclonal antibodies directed to Mtb. 
     
     
         5 . The polynucleotide of  claim 1 , wherein said Mtb polypeptide is detected by either ELISA or Western blotting using a polyclonal antibody directed to Mtb. 
     
     
         6 . The isolated polynucleotide of  claim 1 , further comprising: (a) a 5′ TAP polynucleotide sequence; and (b) a 3′ TAP polynucleotide sequence, wherein said 5′ TAP polynucleotide sequence and said 3′ TAP polynucleotide sequence are operably coupled to said isolated polynucleotide. 
     
     
         7 . The isolated polynucleotide of  claim 6 , wherein the Mtb polynucleotide sequence is selected from the group consisting of: SEQ ID NOS: 46-64, 110-121. 
     
     
         8 . The isolated polynucleotide of  claim 6 , wherein the 5′ TAP polynucleotide sequence comprises a promoter. 
     
     
         9 . The isolated polynucleotide of  claim 6 , wherein the 5′ TAP polynucleotide sequence is selected from the group consisting of: SEQ ID NOS: 2, 3, 6, and 84. 
     
     
         10 . The isolated polynucleotide of  claim 6 , wherein the 3′ TAP polynucleotide sequence comprises a terminator. 
     
     
         11 . The isolated polynucleotide of  claim 6 , wherein the 3′ TAP polynucleotide sequence is selected from the group consisting of: SEQ ID NOS: 4, 5, 7, and 85. 
     
     
         12 . A primer pair for amplifying a Mtb polynucleotide selected from the group consisting of: SEQ ID NOS: 8 and 9; 10 and 11; 12 and 13; 14 and 15; 16 and 17; 18 and 19; 20 and 21; 22 and 23; 24 and 25; 26 and 27; 28 and 29; 30 and 31; 32 and 33; 34 and 35; 36 and 37; 38 and 39; 40 and 41; 42 and 43; 44 and 45; 86 and 87; 88 and 89; 90 and 91; 92 and 93; 94 and 95; 96 and 97; 98 and 99; 100 and 101; 102 and 103; 104 and 105; 106 and, 107; 108 and 109. 
     
     
         13 . A method of generating an immune response in a mammalian host against Mtb comprising: administering to said mammalian host an immunogenic composition comprising at least one nucleic acid selected from the group of SEQ ID NO: 46-64, 110-121, fragments thereof or combinations thereof, wherein said nucleic acid encodes and expresses in vivo at least one immunogenic peptide or polypeptide, whereby said immune response against Mtb is generated. 
     
     
         14 . (canceled) 
     
     
         15 . The method according to  claim 13 , wherein said immunogenic composition further comprises and adjuvant. 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . A kit comprising: a) at least one Mtb immunogenic composition selected from a nucleic acid selected from the group consisting of SEQ ID NO: 46-64, 110-121, fragments thereof or combinations thereof. 
     
     
         19 . The kit of  claim 18 , wherein the kit further comprises an expression system. 
     
     
         20 . The kit of  claim 18  comprising at least two of said immunogenic compositions. 
     
     
         21 . The kit of  claim 20 , comprising at least two of said nucleic acids.