Method for preventing or treating
The present invention is directed to methods of preventing reactivation of active and latent M. tuberculosis infections by administering a pharmaceutical composition comprising a nucleic acid encoding a Mtb72f fusion protein, or a Mtb72f fusion protein or an immunogenic fragment thereof, for example together with an adjuvant. The Mtb72f nucleic acid or fusion protein can be administered with one or more chemotherapeutic agents effective against a M. tuberculosis infection. The methods also provide for shortening the time course of a chemotherapeutic regimen against a M. tuberculosis infection.
1. A method for treating a subject infected with Mycobacterium tuberculosis comprising administering to a subject infected with M. tuberculosis
(a) a pharmaceutical composition comprising an immunologically effective amount of:
(i) a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex and an adjuvant; or
(ii) a nucleic acid encoding a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex, and
(b) one or more chemotherapeutic agents effective against a M. tuberculosis infection
wherein the Mtb72f fusion protein or immunogenic fragment thereof of (i) or encoded by the nucleic acid of (ii) induces an immune response against M. tuberculosis in the subject.
2. The method of claim 1 , wherein the pharmaceutical composition of (a) comprises a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex and an adjuvant.
3. The method of claim 1 , wherein the pharmaceutical composition comprises a nucleic acid encoding a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex.
4. The method of claim 1 , wherein the Mtb72f fusion protein is from Mycobacterium tuberculosis.
5. The method of claim 4 , wherein the Mtb72f fusion protein is a polypeptide comprising residues 8-729 of SEQ ID NO:2.
6. The method of claim 4 , wherein the Mtb72f fusion protein is a polypeptide comprising residues 4-725 of SEQ ID NO:4.
7. The method of claim 2 , wherein the adjuvant is selected from the group consisting of
(i) 3D-MPL and QS21 in a liposome formulation, and
(ii) 3D-MPL and QS21 and an oil in water emulsion.
8. The method of claim 3 , wherein the nucleic acid comprises nucleotides 63-2222 of SEQ ID NO:1.
9. The method of claim 3 , wherein the nucleic acid comprises nucleotides 10-2175 of SEQ ID NO:3.
10. The method of claim 3 , wherein the nucleic acid is administered in an adenovirus vector.
11. The method of claim 3 , wherein the nucleic acid is administered in a mutant Mycobacterium or Bacillus host cell vector.
12. The method of claim 1 , wherein the one or more chemotherapeutic agents effective against a M. tuberculosis infection of (b) is administered over a period of time.
13. The method of claim 12 , wherein the one or more chemotherapeutic agents effective against a M. tuberculosis infection of (b) is administered over about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months or about 1 year.
14. The method of claim 1 , wherein the one or more chemotherapeutic agents is selected from isoniazid and rifampin.
15. The method of claim 1 , wherein the subject is first administered said one or more chemotherapeutic agents of (b) and then administered said pharmaceutical composition of (a).
16. The method of claim 1 , wherein the subject is first administered said pharmaceutical composition of (a), and then administered said one or more chemotherapeutic agents of (b).
17. The method of claim 1 , wherein administration of the one or more chemotherapeutic agents of (b) and the pharmaceutical composition of (a) is initiated concurrently.
18. A method for reducing the time course of chemotherapy for treating a subject infected with Mycobacterium tuberculosis , the method comprising administering to a subject infected with M. tuberculosis
(a) a pharmaceutical composition comprising an immunologically effective amount of:
(i) a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex and an adjuvant; or
(ii) a nucleic acid encoding a Mtb72f fusion protein or an immunogenic fragment thereof from a Mycobacterium species of the tuberculosis complex, and
(b) one or more chemotherapeutic agents effective against a M. tuberculosis infection
wherein the Mtb72f fusion protein or immunogenic fragment thereof which is administered in (i) or encoded by the nucleic acid of (ii) induces an immune response against M. tuberculosis in the subject thereby, and
wherein the time course of chemotherapy against a M. tuberculosis infection in the subject is reduced.