Therapeutic tb vaccine

Abstract

Therapeutic vaccines comprising polypeptides expressed during the latent stage of mycobacteria infection are provided, as are multiphase vaccines, and methods for treating and preventing tuberculosis.

1 . A method for inducing an immune response in an animal to tuberculosis, comprising delivering a composition comprising a mycobacteria polypeptide having amino acid sequence SEQ ID NO: 33 and a pharmaceutically acceptable polymeric carrier bound to the polypeptide or a pharmaceutically acceptable adjuvant. 
     
     
         2 . The method according to  claim 1 , wherein said polypeptide is fused to at least one fusion partner which is an antigen expressed by bacteria within the mycobacteria family, wherein said at least one fusion partner is heterologous to said polypeptide. 
     
     
         3 . The method according to  claim 1 , wherein said polypeptide is lipidated thereby providing a self-adjuvanting effect of the polypeptide. 
     
     
         4 . The method according to  claim 1 , which comprises a polymeric carrier bound by covalent or non-covalent interactions to said polypeptide. 
     
     
         5 . The method according to  claim 4 , wherein the polymeric carrier is a polystyrene. 
     
     
         6 . The method according to  claim 2 , wherein the fusion partner is selected from the polypeptides of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45. 
     
     
         7 . The method according to  claim 6 , wherein the polypeptides are recombinant or synthetic and are delivered in a delivery system comprising an adjuvant. 
     
     
         8 . The method according to  claim 2 , wherein said at least one fusion partner is an antigen expressed by bacteria within the mycobacteria family other than a polypeptide selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45. 
     
     
         9 . The method according to  claim 8 , wherein said at least one fusion partner is selected from the group consisting of ESAT-6, ESAT-6-Ag85B, TB10.4, CFP10, RD1-ORF5, RD1-ORF2, Rv1036, MPB64, MPT64, Ag85A, Ag85B (MPT59), MPB59, Ag85C, 19 kDa lipoprotein, and MPT32. 
     
     
         10 . The method according to  claim 8 , wherein the polypeptides are recombinant or synthetic and are delivered in a delivery system comprising an adjuvant. 
     
     
         11 . The method according to  claim 1 , wherein said animal is a mammal. 
     
     
         12 . The method according to  claim 11 , wherein said mammal is a human. 
     
     
         13 . A method for inducing an immune response in an animal to tuberculosis, comprising delivering one or more mycobacteria polypeptides which are upregulated or expressed during the latent stage of the mycobacteria infection which is characterized by low-oxygen tension in the microenvironment of the mycobacteria and (i) a pharmaceutically acceptable polymeric carrier bound to the one or more polypeptides or (ii) a pharmaceutically acceptable adjuvant, wherein said one or more polypeptides has the amino acid sequence of SEQ ID NO: 33,
 wherein said one or more polypeptides is fused to at least one mycobacteria fusion partner.   
     
     
         14 . The method according to  claim 13 , where the polypeptides are recombinant or synthetic and are delivered in a delivery system comprising an adjuvant. 
     
     
         15 . The method according to  claim 13 , wherein the fusion partner is selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45. 
     
     
         16 . The method according to  claim 15 , wherein the fusion partner is an antigen expressed by bacteria within the mycobacteria family other than a polypeptide selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45. 
     
     
         17 . The method according to  claim 16 , wherein the fusion partner is selected from the group consisting of ESAT-6, ESAT-6-Ag85B, TB10.4, CFP10, RD1-ORF5, RD1-ORF2, Rv1036, MPB64, MPT64, Ag85A, Ag85B (MPT59), MPB59, Ag85C, 19 kDa lipoprotein, and MPT32. 
     
     
         18 . A method for inducing an immune response in an animal to latent tuberculosis, comprising delivering a composition comprising one or more mycobacteria polypeptides which are upregulated or expressed during the latent stage of the mycobacteria infection, wherein one polypeptide has the amino acid sequence of SEQ ID NO: 33. 
     
     
         19 . The method according to  claim 18 , wherein the polypeptides are recombinant or synthetic and are delivered in a delivery system comprising an adjuvant. 
     
     
         20 . The method according to  claim 18 , wherein the fusion partner is selected from SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, and 45.