Global gene regulators (GGR) as vaccine candidates against paratuberculosis

Patent metadata

Field	Value
Publication number	US-11655447-B2
Application number	US-202117221605-A
Country	US
Kind code	B2
Filing date	Apr 2, 2021
Priority date	Mar 12, 2013
Publication date	May 23, 2023
Grant date	May 23, 2023

Abstract

Described herein is a Mycobacterium mutant, comprising at least one mutation in at least one gene sequence encoding global gene regulators (GGRs) selected from the group consisting of sigH, sigL, sigE, ECF-1, and mixtures thereof, wherein the GGR gene is at least partially inactivated. Described herein also is a vaccine based on the mutant and a method of differentiating between subjects that have been infected with Mycobacterium and subjects that have not been infected with Mycobacterium or have been vaccinated with a Mycobacterium vaccine.

First claim

I claim:

1. A Mycobacterium mutant, comprising a mutation in a gene sequence encoding global gene regulators (GGRs), wherein the GGR is sigE, wherein the GGR gene is at least partially inactivated, wherein the Mycobacterium is selected from the group consisting of Mycobacterium avium subspecies paratuberculosis ( M. ap ) and Mycobacterium bovis ( M. bovis ).

2. The mutant of claim 1 , wherein the Mycobacterium is M. ap.

3. The mutant of claim 1 , wherein the Mycobacterium is M. bovis.

4. The mutant of claim 1 , further comprising a mutation in a gene sequence encoding a second GGR, wherein the GGR is M. ap sigH (SEQ ID NO:1) or a sequence substantially identical to SEQ ID NO:1.

5. The mutant of claim 1 , further comprising a mutation in a gene sequence encoding a second GGR, wherein the GGR is M. ap sigL (SEQ ID NO:2) or a sequence substantially identical to SEQ ID NO:2.

6. The mutant of claim 1 , further comprising a mutation in a gene sequence encoding a second GGR, wherein the GGR is M. ap ECF-1 (SEQ ID NO:4) or a sequence substantially identical to SEQ ID NO:4.

7. The mutant of claim 1 , wherein the inactivation is achieved by at least partial deletion of the gene sequence encoding GGRs.

8. The mutant of claim 7 , wherein the inactivation is achieved by a complete deletion of the gene sequence encoding GGRs.

9. The mutant of claim 1 , wherein the inactivation is achieved by at least partial transposon insertion of the gene sequence encoding GGRs.

10. The mutant of claim 9 , wherein the inactivation is achieved by a complete transposon insertion of the gene sequence encoding GGRs.

11. The mutant of claim 1 , wherein the inactivation is achieved by at least partial anti-sense construct of the gene sequence encoding GGRs.

12. The mutant of claim 11 , wherein the inactivation is achieved by a complete anti-sense construct of the gene sequence encoding GGRs.

13. An isolated mycobacterial organism comprising a Mycobacterium mutant according to claim 1 .

14. A Mycobacterium vaccine comprising a Mycobacterium mutant according to claim 1 .

15. The vaccine of claim 14 , wherein the vaccine is physically inactivated.

16. The vaccine of claim 15 , wherein the vaccine is heat inactivated.

17. The vaccine of claim 14 , wherein the vaccine is chemically inactivated.

18. The vaccine of claim 17 , wherein the vaccine is formaldehyde inactivated.

19. The vaccine of claim 14 , wherein the vaccine is a live attenuated vaccine.

20. A Mycobacterium mutant, comprising a mutation in a gene sequence encoding global gene regulators (GGRs), wherein the GGR is sigH, wherein the GGR gene is at least partially inactivated, and wherein the Mycobacterium is Mycobacterium avium subspecies paratuberculosis ( M. ap ).

21. The mutant of claim 20 , wherein the sigH comprises SEQ ID NO:1 or a sequence substantially identical to SEQ ID NO:1.

22. A Mycobacterium vaccine comprising a Mycobacterium mutant according to claim 20 .

Assignees

• Wisconsin Alumni Res Found

Inventors

• Talaat Adel M

Classifications

• C07K14/195

  from bacteria · CPC title

• A61K39/04

  Mycobacterium, e.g. Mycobacterium tuberculosis · CPC title

• C12N1/205

  Bacterial isolates · CPC title

• C12N1/36

  Adaptation or attenuation of cells · CPC title

• C12N1/20 Primary

  Bacteria; Culture media therefor · CPC title