Tuberculosis Compositions And Methods Of Treating Or Preventing Tuberculosis

Abstract

The present disclosure provides fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

1 . A composition or fusion protein comprising at least three  Mycobacterium tuberculosis  (Mtb) antigens, wherein the Mtb antigens are chosen from Rv1009, Rv3136, Rv3615c, Rv2628, Rv2034, and Rv3136 N-terminus. 
     
     
         2 - 7 . (canceled) 
     
     
         8 . The fusion protein according to  claim 1  comprising:
 Rv1009-Rv3615c-Rv3136; 
 Rv1009-Rv2034-Rv3136; 
 Rv2034-Rv1009-Rv3136; 
 Rv3136-Rv2034-Rv1009. 
 
     
     
         9 . The fusion protein according to  claim 8  wherein:
 Rv1009 comprises the amino acid sequence set forth in SEQ ID NO:2 or SEQ ID NO:4; 
 Rv3136 comprises the amino acid sequence set forth in SEQ ID NO:8; 
 Rv3615c comprises the amino acid sequence set forth in SEQ ID NO: 11; 
 Rv2628 comprises the amino acid sequence set forth in SEQ ID NO: 14; 
 Rv2034 comprises the amino acid sequence set forth in SEQ ID NO: 16; and 
 Rv3136Nt comprises the amino acid sequence set forth in SEQ ID NO: 18. 
 
     
     
         10 . The fusion protein according to  claim 8  wherein:
 Rv1009 is encoded by a nucleotide sequence set forth in SEQ ID NO:1 or SEQ ID NO:3; 
 Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7; 
 Rv3615c is encoded by a nucleotide sequence set forth in SEQ ID NO:9 or SEQ ID NO:10; 
 Rv2628 is encoded by a nucleotide sequence set forth in SEQ ID NO: 12 or SEQ ID NO:13; 
 Rv2034 is encoded by a nucleotide sequence set forth in SEQ ID NO: 15; and 
 Rv3136Nt is encoded by a nucleotide sequence set forth in SEQ ID NO:17. 
 
     
     
         11 . The fusion protein according to  claim 8  wherein:
 Rv1009-Rv3615c-Rv3136 comprises the amino acid sequence set forth in SEQ ID NO:39; 
 Rv1009-Rv2034-Rv3136 comprises the amino acid sequence set forth in SEQ ID NO:41; 
 Rv2034-Rv1009-Rv3136 comprises the amino acid sequence set forth in SEQ ID NO:47; 
 Rv3136-Rv2034-Rv1009 comprises the amino acid sequence set forth in SEQ ID NO:49. 
 
     
     
         12 . The fusion protein according to  claim 8  wherein:
 Rv1009-Rv3615c-Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO:38; 
 Rv1009-Rv2034-Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO:40; 
 Rv1009-Rv2628-Rv3615c-Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO:42; 
 Rv1009-Rv2034-Rv2628-Rv3615c-Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO:44; 
 Rv2034-Rv1009-Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO:46; 
 Rv3136-Rv2034-Rv1009 is encoded by a nucleotide sequence set forth in SEQ ID NO:48; 
 Rv1009-Rv3615c-Rv2034-Rv2628 is encoded by a nucleotide sequence set forth in SEQ ID NO:50; 
 Rv3615c-Rv2034-Rv2628-Rv1009 is encoded by a nucleotide sequence set forth in SEQ ID NO: 52; 
 Rv2034-Rv3615c-Rv2628-Rv3136 is encoded by a nucleotide sequence set forth in SEQ ID NO: 54; 
 Rv3136-Rv2628-Rv3615c-Rv2034 is encoded by a nucleotide sequence set forth in SEQ ID NO:56; 
 Rv1009-Rv3136Nt-Rv2628-Rv2034-Rv3615c is encoded by a nucleotide sequence set forth in SEQ ID NO:58; 
 Rv2034-Rv3615c-Rv3136Nt-Rv2628-Rv1009 is encoded by a nucleotide sequence set forth in SEQ ID NO:60; 
 Rv3615c-Rv2628-Rv1009-Rv3136Nt-Rv2034 is encoded by a nucleotide sequence set forth in SEQ ID NO:62; 
 Rv1009-Rv2628-Rv3136Nt-Rv2034-Rv3615c is encoded by a nucleotide sequence set forth in SEQ ID NO:70; 
 Rv2628-Rv3136Nt-Rv1009-Rv2034-Rv3615c is encoded by a nucleotide sequence set forth in SEQ ID NO:72; and 
 Rv2628-Rv3136Nt-Rv2034-Rv3615c-Rv1009 is encoded by a nucleotide sequence set forth in SEQ ID NO:74. 
 
     
     
         13 . A composition or fusion protein comprising at least two  Mycobacterium tuberculosis  (Mtb) antigens, wherein the Mtb antigens are Rv1733 and Rv2626c. 
     
     
         14 . The fusion protein according to  claim 13  comprising Rv1733-Rv2626c. 
     
     
         15 . A composition or fusion protein comprising at least three  Mycobacterium tuberculosis  (Mtb) antigens, wherein the Mtb antigens are chosen from Ag85A, Ag85B, Rv3407, RpfA, RpfC, and RpfD. 
     
     
         16 . The composition or fusion protein according to  claim 15  comprising:
 Ag85A, Ag85B, and Rv3407 Mtb antigens; or 
 RpfA, RpfC, and RpfD Mtb antigens. 
 
     
     
         17 . The fusion protein according to  claim 16  comprising:
 Ag85A-Ag85B-Rv3407; or 
 RpfA-RpfC-RpfD. 
 
     
     
         18 . A pharmaceutical composition comprising the composition or fusion protein according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         19 . A vector comprising a nucleic acid molecule encoding the fusion protein according to  claim 1 . 
     
     
         20 . A cell comprising the vector according to  claim 19 . 
     
     
         21 . A method of eliciting an immune response against  Mycobacterium tuberculosis  in a mammal comprising administering to the mammal an immunologically sufficient amount of the composition or fusion protein according to  claim 1 . 
     
     
         22 . The method of  claim 21  wherein the composition or fusion protein is administered to the mammal in the form of an aerosol.