Vaccines comprising TB10.4

Abstract

Vaccination with the combination of Ag85B-TB10.4 and IC31® adjuvant generated a high amount of polyfunctional CD4 + T cells expressing high levels of IFN-γ, TNF-α, and IL-2. This in turn led to significant protection against infection with M. tuberculosis in the mouse aerosol challenge model of tuberculosis. Both the immunogenicity of the vaccine and its ability to protect against TB infection was highly dependent on the antigen dose. Thus, whereas the standard antigen dose of 5 μg, as well as 15 μg, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 μg increased both the immunogenicity of the vaccine as well as its protective efficacy to a level comparable to that observed in BCG vaccinated mice. Thus, the IC31® adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.

The invention claimed is: 
     
       1. A method of inducing an immune response against M. tuberculosis in a mammal human, the method comprising introducing into said mammal human an immunogenic composition comprising
 a TB10.4 protein, 
 an Ag85-complex protein, and 
 an adjuvant comprising at least one polycationic peptide and at least one polydeoxyinosinic-deoxycytidylic acid, 
 wherein the total amount of the TB10.4 protein and the Ag85-complex protein is less than about 1 μg about 5 μg to about 25 μg. 
 
     
     
       2. The method according to  claim 1 , wherein the TB10.4 protein and the Ag85-complex protein are present as a fusion protein. 
     
     
       3. The method according to  claim 2 , wherein the fusion protein is present in an amount equal to about 0.5 μg 10 μg to about 25 μg. 
     
     
       4. The method according to claim  2  3, wherein the fusion protein is present in an amount equal to about 0.1 μg 15 μg. 
     
     
       5. The method according to  claim 1 , wherein the Ag85-complex protein is an Ag85B protein. 
     
     
       6. The method according to  claim 1 , wherein the at least one oligonucleotide is a TLR9 agonist. 
     
     
       7. The method according to  claim 1 , wherein the adjuvant is a mixture of [peptide] NH2-KLKLLLLLKLK-COOH (SEQ ID NO: 1) and [oligonucleotide] 5′-ICI CIC ICI CIC ICI CIC ICI CIC IC-3′ (SEQ ID NO:2). 
     
     
       8. The method according to  claim 1 , wherein said mammal is a human. 
     
     
       9. A method of inducing protection against M. tuberculosis in a mammal human, the method comprising introducing into said mammal human an immunogenic composition comprising
 a TB10.4 protein, 
 an Ag85-complex protein, and 
 an adjuvant comprising at least one polycationic peptide and at least oligonucleotide-5′-ICI CIC ICI CIC ICI CIC ICI CIC IC-3′ (SEQ ID NO:2), 
 wherein the total amount of the TB10.4 protein and the Ag85-complex protein is less than about 1 μg about 5 μg to about 25 μg. 
 
     
     
       10. The method according to  claim 9 , wherein the TB10.4 protein and the Ag85-complex protein are present as a fusion protein. 
     
     
       11. The method according to  claim 10 , wherein the fusion protein is present in an amount equal to about 0.5 μg 10 μg to about 25 μg. 
     
     
       12. The method according to claim  10  11, wherein the fusion protein is present in an amount equal to about 0.1 μg 15 μg. 
     
     
       13. The method according to  claim 9 , wherein the Ag85-complex protein is an Ag85B protein. 
     
     
       14. The method according to  claim 9 , wherein the at least one oligonucleotide is a TLR9 agonist. 
     
     
       15. The method according to  claim 9 , wherein the adjuvant is a mixture of peptide NH 2 -KLKLLLLLKLK-COOH (SEQ ID NO:1) and oligonucleotide 5′-ICI CIC ICI CIC ICI CIC ICI CIC IC-3′ (SEQ ID NO:2). 
     
     
       16. The method according to  claim 9 , wherein said mammal is a human. 
     
     
       17. A method of inducing an immune response against M. tuberculosis in a mammal human, the method comprising introducing into said mammal human an immunogenic composition comprising
 a TB10.4 protein, 
 an Ag85-complex protein, and 
 an adjuvant comprising at least one polycationic peptide and at least one polydeoxyinosinic-deoxycytidylic acid, 
 wherein the total amount of the TB10.4 protein and the Ag85-complex protein ranges from 0.1 μg to 1 μg is about 15 μg. 
 
     
     
       18. The method according to  claim 17 , wherein the TB10.4 protein and the Ag85-complex protein are present as a fusion protein. 
     
     
       19. The method according to  claim 18 , wherein the fusion protein is present in an amount equal to about 0.5 μg. 
     
     
       20. The method according to  claim 17 , wherein the adjuvant is a mixture of [peptide] NH2-KLKLLLLLKLK-COOH (SEQ ID NO: 1) and [oligonucleotide] 5′-ICI CIC ICI CIC ICI CIC ICI CIC IC-3′ (SEQ ID NO:2). 
     
     
       21. The method according to claim 1, wherein the total amount of the TB10.4 protein and the Ag85-complex protein is about 10 μg to about 25 μg.  
     
     
       22. The method according to claim 21, wherein the total amount of the TB10.4 protein and the Ag85-complex protein is about 15 μg.  
     
     
       23. The method according to claim 9, wherein the total amount of the TB10.4 protein and the Ag85-complex protein is about 15 μg.