Immunizing compositions and methods of use
The present invention provides compositions including siderophore receptor polypeptides and porins from gram negative microbes, and preferably, lipopolysaccharide at a concentration of no greater than about 10.0 endotoxin units per milliliter. The present invention also provides methods of making and methods of using such compositions, including inducing the production of antibody in an animal.
1. A composition comprising:
an isolated whole cell preparation of gram negative microbes, wherein the gram negative microbes comprise:
at least two siderophore receptor polypeptides (SRPs); and
at least two porins; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbes comprise members of the family Vibrionaceae.
2. A composition comprising:
an isolated whole cell preparation of gram negative microbes, wherein the gram negative microbes comprise:
at least two siderophore receptor polypeptides (SRPs); and
at least two porins; and
a pharmaceutically acceptable carrier:,
wherein the gram negative microbes comprise Campylobacter spp.
3. A composition comprising:
an isolated whole cell preparation of gram negative microbes, wherein the gram negative microbes comprise:
at least two siderophore receptor polypeptides (SRPs); and
at least two porins; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbes comprise Actinobacillus spp., Haemophilus spp., Myxcobacteria spp., Sporocytophaga spp., Chondrococcus spp., Cytophaga spp., Flexibacter spp., Flavobacterium spp., Aeromonas spp., or any combination thereof.
4. A composition comprising:
an isolated whole cell preparation of gram negative microbes, wherein the gram negative microbes comprise:
at least two siderophore receptor polypeptides (SRPs) expressed by the gram negative microbe when the gram negative microbe is grown in the presence of 2,2-dipyridyl; and
at least two porins; and
a pharmaceutically acceptable carrier.
5. The composition of claim 4 wherein the SRPs comprise SRPs that are expressed by the gram negative microbe when the gram negative microbe is grown in the presence of 24 μg/mL 2,2-dipyridyl.
6. A composition comprising:
an isolated whole cell preparation of gram negative microbes, wherein the gram negative microbes comprise:
at least two siderophore receptor polypeptides (SRPs), wherein at least one SRP is not expressed by the gram negative microbe at a detectable level when the gram negative microbe is grown in the absence of 2,2-dipyridyl; and
at least two porins; and
a pharmaceutically acceptable carrier.
7. The composition of claim 6 wherein at least one SRP comprises an SRP that is not expressed by the gram negative microbe at a detectable level when the gram negative microbe is grown in the absence of 24 μg/mL 2,2-dipyridyl.
8. The composition of claim 1 further comprising an adjuvant.
9. The composition of claim 1 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
10. The composition of claim 1 wherein the pharmaceutically acceptable carrier comprises an implant.
11. A composition comprising:
whole cells comprising:
a plurality of siderophore receptor polypeptides (SRPs) expressed by a gram negative microbe; and
a plurality of porins expressed by the gram negative microbe; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbes comprise members of the family Vibrionaceae.
12. A composition comprising:
whole cells comprising:
a plurality of siderophore receptor polypeptides (SRPs) expressed by a gram negative microbe; and
a plurality of porins expressed by the gram negative microbe; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbes comprise Campylobacter spp.
13. A composition comprising:
whole cells comprising:
a plurality of siderophore receptor polypeptides (SRPs) expressed by a gram negative microbe; and
a plurality of porins expressed by the gram negative microbe; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbes comprise Actinobacillus spp., Haemophilus spp., Myxcobacteria spp., Sporocytophaga spp., Chondrococcus spp., Cytophaga spp., Flexibacter spp., Flavobacterium spp., Aeromonas spp., or any combination thereof.
14. A composition comprising:
whole cells comprising:
a plurality of siderophore receptor polypeptides (SRPs) expressed by a gram negative microbe when the gram negative microbe is grown in the presence of 2,2-dipyridyl; and
a plurality of porins expressed by the gram negative microbe; and
a pharmaceutically acceptable carrier.
15. The composition of claim 14 wherein the SRPs comprise SRPs that are expressed by the gram negative microbe when the gram negative microbe is grown in the presence of 24 μg/mL 2,2-dipyridyl.
16. A composition comprising:
whole cells comprising:
a plurality of siderophore receptor polypeptides (SRPs) expressed by a gram negative microbe, wherein at least one SRP is not expressed by the gram negative microbe at a detectable level when the gram negative microbe is grown in the absence of 2,2-dipyridyl; and
a plurality of porins expressed by the gram negative microbe; and
a pharmaceutically acceptable carrier.
17. The composition of claim 16 wherein at least one SRP comprises an SRP that is not expressed by the gram negative microbe at a detectable level when the gram negative microbe is grown in the absence of 24 μg/mL 2,2-dipyridyl.
18. The composition of claim 11 further comprising an adjuvant.
19. The composition of claim 11 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
20. The composition of claim 11 wherein the pharmaceutically acceptable carrier comprises an implant.
21. A composition comprising:
an isolated whole cell preparation of gram negative microbes, wherein the gram negative microbes comprise:
at least two siderophore receptor polypeptides (SRPs); and
at least two porins; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbe comprises an E. coli mutant lacking outer oligosaccharide side chains of LPS.
22. A composition comprising:
whole cells comprising:
a plurality of siderophore receptor polypeptides (SRPs) expressed by a gram negative microbe; and
a plurality of porins expressed by the gram negative microbe; and
a pharmaceutically acceptable carrier;
wherein the gram negative microbe comprises an E. coli mutant lacking outer oligosaccharide side chains of LPS.
23. The composition of claim 2 further comprising an adjuvant.
24. The composition of claim 2 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
25. The composition of claim 2 wherein the pharmaceutically acceptable carrier comprises an implant.
26. The composition of claim 3 further comprising an adjuvant.
27. The composition of claim 3 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
28. The composition of claim 3 wherein the pharmaceutically acceptable carrier comprises an implant.
29. The composition of claim 4 further comprising an adjuvant.
30. The composition of claim 4 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
31. The composition of claim 4 wherein the pharmaceutically acceptable carrier comprises an implant.
32. The composition of claim 6 further comprising an adjuvant.
33. The composition of claim 6 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
34. The composition of claim 6 wherein the pharmaceutically acceptable carrier comprises an implant.
35. The composition of claim 12 further comprising an adjuvant.
36. The composition of claim 12 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
37. The composition of claim 12 wherein the pharmaceutically acceptable carrier comprises an implant.
38. The composition of claim 13 further comprising an adjuvant.
39. The composition of claim 13 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
40. The composition of claim 13 wherein the pharmaceutically acceptable carrier comprises an implant.
41. The composition of claim 14 further comprising an adjuvant.
42. The composition of claim 14 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
43. The composition of claim 14 wherein the pharmaceutically acceptable carrier comprises an implant.
44. The composition of claim 16 further comprising an adjuvant.
45. The composition of claim 16 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
46. The composition of claim 16 wherein the pharmaceutically acceptable carrier comprises an implant.
47. The composition of claim 21 further comprising an adjuvant.
48. The composition of claim 21 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
49. The composition of claim 21 wherein the pharmaceutically acceptable carrier comprises an implant.
50. The composition of claim 22 further comprising an adjuvant.
51. The composition of claim 22 wherein the pharmaceutically acceptable carrier comprises a biocompatible matrix.
52. The composition of claim 22 wherein the pharmaceutically acceptable carrier comprises an implant.