Attenuated
The present invention provides attenuated M. haemolitica strains that elicit an immune response in animal against M. haemolitica , compositions comprising said strains, methods of vaccination against M. haemolitica , and kits for use with such methods and compositions. The invention further provides multi-valent vaccines, which provide protective immunity when administered in an effective amount to animals susceptible to “shipping fever” or bovine respiratory disease.
1. A non-adjuvanted, intranasal vaccine comprising an attenuated Mannheimia haemolytica ( M haemolytica ) A1 strain and an attenuated M haemolytica A6 strain, which vaccine provides a safe and protective immune response in a bovine animal against both M. haemolytica strains A1 and A6, or diseases caused by M. haemolytica strains A1 and A6.
2. The vaccine of claim 1 , wherein both the A1 and A6 strains contain nucleic acid deletions in their respective leukotoxin A (lktA) genes, which deletions have rendered the strains attenuated relative to the virulent parental strains A1 and A6 from which the attenuated strains A1and A6 were produced.
3. The vaccine of claim 1 , consisting essentially of the attenuated A1 and A6 strains.
4. The vaccine of claim 1 , further comprising an additional antigen, which is capable of eliciting a safe and effective response in said bovine against a bovine disease or pathogen other than M haemolytica.
5. The vaccine of claim 1 , wherein a safe and protective intranasal dose of the vaccine comprises from about 1.19 ×10 6 to 1.19 ×10 7 CFU of the attenuated A1 strain and from about 9.2 ×10 5 to 9.2 ×10 6 CFU of the attenuated A6 strain.
6. The vaccine of claim 1 , further comprising a pharmaceutically or veterinary acceptable vehicle, diluent or excipient and from about 1.19 ×10 6 to 1.19 ×10 7 CFU of the attenuated A1 strain and from about 9.2 ×10 5 to 9.2 ×10 6 CFU of the attenuated A6 strain.
7. The vaccine of claim 1 , provided in lyophilized form.
8. The vaccine of claim 1 , which provides the protective immune response in the bovine against an experimental challenge of about 1.09 ×10 9 CFU of virulent M. haemolytica strain A6.
9. The vaccine of claim 1 , which provides the protective immune response in the bovine against an experimental challenge of about 2.4 ×10 9 CFU of virulent M. haemolytica strain A1.
10. The vaccine of claim 1 , further comprising at least two additional antigens associated with a bovine pathogen other than M haemolytica.
11. A method of vaccinating an animal comprising administering at least one dose of the vaccine of claim 1 .
12. The method of claim 11 , wherein the animal is a bovine.
13. The method of claim 12 , wherein the bovine is a calf that is 28 days or older.
14. The method of claim 13 , wherein the vaccine is administered in about equal portions to both of the anima's nostrils.
15. An immunological composition suitable for the prevention of bovine respiratory disease caused by M haemolytica , comprising the vaccine of claim 1 , and further comprising an immunologically effective amount of an attenuated Pasteurella multocida ( P. multocida ) strain and an attenuated Histophilus somni ( H. somni ) strain.
16. The composition of claim 15 , comprising from about 1.19 ×10 6 CFU to about 1.19 ×10 7 CFU of the attenuated A1 strain and from about 9.2 ×10 5 CFU to about 9.2 ×10 6 CFU of the attenuated A6 strain.
17. The composition of claim 15 , consisting essentially of the attenuated M haemolytica A1 and A6 strains, the attenuated P. multocida strain and the attenuated H. somni strain.
18. The composition of claim 17 , provided in lyophilized form inside of a sterile vial.
19. A kit for preventing bovine respiratory disease comprising effective amounts of an immunological composition, comprising a non-adjuvanted, intranasal vaccine comprising an attenuated M. haemolytica A1 strain and an attenuated M. haemolytica A6 strain, wherein the vaccine provides a safe and protective immune response in a bovine animal against both M. haemolytica strains A1 and A6, or diseases caused by M. haemolytica strains A1 and A6, wherein the kit further comprising an immunologically effective amount of an attenuated P. multocida strain and an attenuated H. somni strain, provided in lyophilized form, and, a diluent for resuspending the lyophilized, attenuated strains.