Vaccines comprising tb 10.4

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.

1 . An immunogenic composition comprising
 a TB10.4 protein and   an Ag85-complex protein,   wherein the total amount of the TB10.4 protein and the Ag85-complex protein is less than about 25 μg, provided that the composition excludes dimethyl dioctadecyl ammonium bromide (DDA).   
     
     
         2 . An immunogenic composition according to  claim 1 , wherein the TB10.4 protein and the Ag85-complex protein are present as a fusion protein. 
     
     
         3 . An immunogenic composition according to  claim 1 , further comprising an adjuvant. 
     
     
         4 . 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 oligonucleotide,   wherein the total amount of the TB10.4 protein and the Ag85-complex protein is less than about 25 μg.   
     
     
         5 . The immunogenic composition according to  claim 4 , wherein the Ag85-complex protein is an Ag85B protein. 
     
     
         6 . The immunogenic composition according to  claim 4 , wherein the fusion protein is present in an amount of less than about 10 μg. 
     
     
         7 . The immunogenic composition according to  claim 4 , wherein the fusion protein is present in an amount equal to about 0.5 μg. 
     
     
         8 . The immunogenic composition according to  claim 4 , wherein the at least one oligonucleotide is a TLR9 agonist. 
     
     
         9 . The immunogenic composition according to  claim 4 , 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). 
     
     
         10 . The immunogenic composition according to  claim 9 , wherein the adjuvant is IC31® adjuvant. 
     
     
         11 . A vaccine comprising
 a TB10.4 protein,   an Ag85-complex protein, and   an adjuvant comprising at least one polycationic peptide and at least one oligonucleotide,   wherein the total amount of the TB10.4 protein and the Ag85-complex protein is less than about 25 μg.   
     
     
         12 . The vaccine according to  claim 11 , wherein the Ag85-complex protein is an Ag85B protein. 
     
     
         13 . The vaccine according to  claim 11 , wherein the total amount of TB10.4 protein and the Ag85-complex protein less than about 10 μg. 
     
     
         14 . The vaccine according to  claim 13 , wherein the total amount of TB10.4 protein and the Ag85-complex protein equal to about 0.5 μg. 
     
     
         15 . The vaccine according to  claim 11 , wherein the at least one oligonucleotide is a TLR9 agonist. 
     
     
         16 . The vaccine according to  claim 11 , 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). 
     
     
         17 . The vaccine according to  claim 16 , wherein the adjuvant is IC31® adjuvant. 
     
     
         18 . A method of inducing protection against  M. tuberculosis  in a mammal, the method comprising introducing into the mammal an immunogenic composition according to  claim 1 . 
     
     
         19 . A method of inducing protection against  M. tuberculosis  in a mammal, the method comprising introducing into the mammal an immunogenic composition according to  claim 4 . 
     
     
         20 . A method of inducing an immune response against  M. tuberculosis  in a mammal, the method comprising introducing into the mammal an immunogenic composition according to  claim 1 . 
     
     
         21 . The method according to  claim 20 , wherein said mammal is a human.