Modified live vaccine of Mycoplasma bovis, methods of producing modified live Mycoplasma bovis vaccines, combination vaccines and methods of treatment

Patent metadata

Field	Value
Publication number	US-9339533-B2
Application number	US-76608410-A
Country	US
Kind code	B2
Filing date	Apr 23, 2010
Priority date	Apr 24, 2009
Publication date	May 17, 2016
Grant date	May 17, 2016

Abstract

The present invention relates to new attenuated M. bovis bacteria strains passaged at least 110 times. Moreover, the present invention also provides immunogenic compositions comprising live bacteria of any of those attenuated M. bovis bacteria strain, their manufacture and use for the treatment and prophylaxis of M. bovis infections and combinations with other veterinary vaccines or medicaments.

First claim

The invention claimed is:

1. An attenuated, avirulent Mycoplasma bovis ( M. bovis ) bacterium strain, wherein the bacterium is passaged more than 110 times and wherein the attenuated, avirulent M. bovis strain is selected from the group consisting of:
a. the attenuated M. bovis bacteria strain deposited with the American Type Culture Collection (ATCC) under accession number PTA-9666, and
b. the attenuated M. bovis bacteria strain deposited with the ATCC under accession number PTA-9667.

2. The attenuated, avirulent M. bovis bacterium strain according to claim 1 , wherein the bacterium is passaged more than 135 times.

3. A method of attenuating M. bovis , comprising,
a. passaging M. bovis bacteria according to claim 1 more than 110 times to produce a cultured M. bovis bacteria;
b. obtaining the cultured M. bovis bacteria;
c. testing the cultured M. bovis bacteria obtained under step b) for their pathogenicity and immunogenicity; and
d. propagating the non-pathogenic, but immunogenic M. bovis bacteria to obtain the attenuated M. bovis bacteria.

4. The method according to claim 3 , wherein the M. bovis bacteria are passaged in vitro.

5. The method according to claim 3 , wherein the pathogenicity testing comprises:
e. infecting cattle with the passaged M. bovis bacteria; and
f. monitoring the infected cattle for developing clinical symptoms of a M. bovis infection and
monitoring the development of the humoral antibody response against M. bovis in the infected cattle.

6. The attenuated, avirulent M. bovis bacterium strain according to claim 1 , wherein the bacterium strain comprises at least 1.0E7 CFU of the live bacteria of the attenuated, avirulent M. bovis bacteria per dose.

7. The attenuated, avirulent M. bovis bacterium strain according to claim 1 , wherein one dose is 1 or 2 ml.

8. A method for the treatment or prophylaxis of infections caused by M. bovis , comprising, administering an effective amount of the attenuated, avirulent M. bovis bacterium strain according to claim 1 to an animal, wherein said treatment or prophylaxis is selected from the group consisting of reducing signs of M. bovis infection, reducing the severity of or incidence of clinical signs of M. bovis infection, reducing the mortality of animals from M. bovis infection, and combinations thereof.

9. The method according to claim 8 , wherein only a single dose is administered to said animal.

10. The method according to claim 8 , wherein the attenuated, avirulent M. bovis bacterium strain is administered to animals from day 1 of age.

11. The method according to claim 8 , wherein two doses are administered to said animal.

12. The method according to claim 11 , wherein a second dose is administered at least 10 days after the first administration.

13. The method according to claim 8 , wherein the animal is cattle.

14. A method for reducing the incidence of mortality and/or euthanasia of animals resulting from infection by M. bovis comprising administering the attenuated, avirulent M. bovis bacterium strain of claim 1 to an animal.

15. The method of claim 14 , wherein said mortality is reduced by at least 56%.

16. The method of claim 14 , wherein said attenuated, avirulent M. bovis bacterium strain is administered as a single dose.

17. An attenuated, avirulent M. bovis bacterium strain for the treatment and/or prophylaxis of cattle against microbiological infections, wherein said immunogenic composition comprises at least one M. bovis bacteria according to claim 1 ; and one or more further immunologically active component(s) effective for the treatment and/or prophylaxis of microbiological infection in cattle caused by a cattle pathogen other than M. bovis.

18. The attenuated, avirulent M. bovis bacterium strain according to claim 17 , wherein said microbiological infection in cattle caused by a cattle pathogen other than M. bovis is caused by one or more immunogenic components selected from the group consisting of: Bovine viral diarrhea virus (BVDV), Parainfluenza-3 Virus (PI-3), Infectious Bovine Rhinotracheitis virus (IBR), Bovine Respiratory Syncytial Virus (BRSV), Bovine Herpesvirus (BHV), Bovine Rotavirus (BRV), Bovine Enterovirus (BEV), Bovine Coronovirus (BCV), Bovine Rabies (BR), Bovine Parvovirus (BPV), Adenovirus Astrovirus, Mannheimia haemolytica (formerly Pasteurella haemolytica ), Pasteurella multocida, Haemophilus somnus ( Histophilus ovis and Haemophilus agni ), Actinomyces ( Corynebacterium ), Actinomyces pyogenes, Chlamydia psittaci, Campylobacter fetus venerealis and Campylobacter fetus fetus (formerly C. fetus intestinalis ), Leptospira interrogans, Leptospira hardjo, Leptospira pomona , and Leptospira grippotyphosa, Leptospira canicola, Leptospira grippotyphosa, Leptospira hardjo ( Leptospira hardjoprajitno and Leptospira hardjo - bovis ), Brucella abortus, Brucella suis and Brucella melitensis, Listeria monocytogenes, Chlamydia psittaci, Clostridium chauvoei, Clostridium septicum, Clostridium haemolyticum, Clostridium novyi, Clostridium sordellii, Clostridium perfringens, Clostridium tetani, Moraxella bovis, Klebsiella spp, Klebsiella pneumoniae, Salmonella typhimurium; Salmonella newport, Mycobacterium avium paratuberculosis, Cryptsporidium parvum, Cryptsporidium hominis, Staphylococcus aureus, Streptococcus dysgalactiae, Streptococcus uberis, Streptococcus agalactiae, Escherichia coli, Mycoplasma spp, Mycoplasma dispar , and Ureaplasma spp., Tritrichomonas foetus, Trichophyton verrucosum, Trichophyton mentagrophytes, Trichophyton sarkisovii, Neospora caninum (formerly Toxoplasma gondii ), Babesia bigemina and Babesia bovis, Dictyocaulus viviparous (Lungworm disease), and combinations thereof.

19. The attenuated, avirulent M. bovis bacterium strain according to claim 17 , wherein said immunogenic composition is a single-dose administration.

20. A method of co-administration of two or more immunologically active components to a cattle comprising, administering to said cattle an attenuated, avirulent M. bovis bacterium strain according to claim 1 , and one or more further immunologically active component(s) effective for the treatment and/or prophylaxis of infections caused by a further cattle relevant pathogen other than M. bovis.

21. The method according to claim 20 , wherein said attenuated, avirulent M. bovis bacterium strain and said immunologically active component(s) are administered separately.

22. The method according to claim 20 , wherein the separate co-administration of the attenuated, avirulent M. bovis bacterium strain and said immunologically active component(s) occurs within 2 days.

23. The method according to claim 20 , wherein the two or more immunologically active components which comprise an attenuated, avirulent M. bovis bacterium strain and one or more immunologically active component(s) effective for the treatment and/or prophylaxis of infections caused by a further cattle relevant pathogen other than M. bovis are formulated as fix-dose combination vaccine.

24. The method according to claim 20 , wherein the two or more immunologically active components which comprise an attenuated, avirulent M. bovis bacterium strain and one or more immunologically active component(s) effective for the treatment and/or prophylaxis of infections caused by a further cattle relevant pathogen other than M. bovis are administered to

Assignees

• Beck Michael
• KNITTEL Jeffrey
• Boehringer Ingelheim Vetmed

Inventors

• Beck Michael
• KNITTEL Jeffrey

Classifications

• A61P33/00

  Antiparasitic agents · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K2039/522

  avirulent or attenuated · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title