Therapeutic vaccination against active tuberculosis

Abstract

The invention provides a method for therapeutic treatment of a patient having active tuberculosis (TB), the method comprising: administering to the patient a recombinant adenovirus vector that comprises nucleic acid encoding the Ag85A, Ag85B and TB10.4 antigens of Mycobactium tuberculosis (Mtb). Advantageously, the method can be used to shorten conventional drug therapy for treating active TB.

What is claimed is: 
     
         1 . A method for treating a patient having active tuberculosis (TB), the method comprising:
 administering to the patient a recombinant adenovirus vector comprising nucleic acid encoding Ag85A, Ag85B and TB10.4 antigens of  Mycobacterium tuberculosis  (Mtb).   
     
     
         2 . The method according to  claim 1 , further comprising:
 treating the patient further with drug therapy.   
     
     
         3 . The method according to  claim 2 , wherein the patient is treated with drug therapy for a reduced period as compared to standard drug therapy. 
     
     
         4 . The method according to  claim 3 , wherein treating the patient with drug therapy for a reduced period comprises administering therapeutic drugs to the patient for a period of between one week and four months. 
     
     
         5 . The method according to  claim 3 , wherein standard drug therapy comprises:
 daily administration of isoniazid, rifampin, pyrazinamide, and ethambutol for a period of two months,   followed by administration of rifampin and isoniazid with or without ethambutol daily or three times per week for a period of four months.   
     
     
         6 . The method according to  claim 3 , wherein the bacterial burden of Mtb as measured in a group of patients at a given time after the initiation of drug therapy is lower as compared to the burden at the same time point without the administration of said adenovirus. 
     
     
         7 . The method according to  claim 3 , wherein the relapse rate of active TB as measured in a population of patients after the therapeutic drug therapy for a reduced period is the same as or less than for a standard drug regimen for a normal period without the administration of the adenovirus. 
     
     
         8 . The method according to  claim 3 , wherein the nucleic acid encodes Ag85A, Ag85B and TB 10.4 antigens as a fusion protein. 
     
     
         9 . The method according to  claim 3 , wherein the adenovirus is a replication-deficient human adenovirus of serotype 35. 
     
     
         10 . The method according to  claim 3 , wherein the adenovirus is a replication-deficient human adenovirus of serotype 26. 
     
     
         11 . The method according to  claim 3 , wherein the adenovirus vector is administered in a heterologous prime-boost regimen. 
     
     
         12 . The method according to  claim 11 , wherein the heterologous prime-boost regimen comprises administration of vectors of human adenovirus serotype 35 and of human adenovirus serotype 26. 
     
     
         13 . The method according to  claim 3 , wherein the TB is pulmonary TB. 
     
     
         14 . The method according to  claim 3 , wherein the patient has an infection with multidrug-resistant Mtb (MDR-TB) or extremely drug-resistant Mtb (XDR-TB). 
     
     
         15 . The method according to  claim 3 , wherein a recombinant adenovirus vector comprising nucleic acid encoding Ag85A, Ag85B, and TB10.4 antigens of Mtb is administered to the patient more than once. 
     
     
         16 . The method according to  claim 3 , wherein the administration of the recombinant adenovirus vector induces a CD8+ T-cell response in the patient against at least one of the antigens. 
     
     
         17 . The method according to  claim 3 , wherein the administration of the recombinant adenovirus vector induces a CD4+ T-cell response in the patient against at least one of the antigens. 
     
     
         18 . A method for inducing an immune response against antigens of  Mycobacterium tuberculosis  (Mtb) in a subject infected with Mtb, the method comprising:
 administering to the subject a recombinant adenovirus vector comprising nucleic acid encoding Ag85A, Ag85B, and TB10.4 antigens of Mtb to express said antigens and to induce an immune response to at least one of the antigens in the subject.   
     
     
         19 . The method according to  claim 18 , further comprising administering to the subject one or more antibiotic drugs. 
     
     
         20 . The method according to  claim 19 , wherein administering of antibiotic drugs is performed in a regimen that is shorter in duration than a standard regimen of administering the antibiotic drugs to which the subject would be eligible in the absence of administering the adenovirus.