Bacteriophage preparations and methods of use thereof
View Patent ↗Disclosed herein are purified bacteriophage preparations that effectively lyse a plurality of C. perfringens strains. In one embodiment, a purified bacteriophage preparation includes four or more C. perfringens -specific bacteriophage, wherein each bacteriophage has lytic activity against at least five Clostridium species strains. In another embodiment, the purified bacteriophage preparation includes five or more C. perfringens -specific bacteriophage.
1. A method of reducing chicken mortality due to C. perfringens infections comprising administering a purified bacteriophage preparation comprising CPAS-12 (accession number PTA-8479), CPAS-15 (accession number PTA-8480), CPAS-16 (accession number PTA-8481) and CPLV-42 (accession number PTA-8483) wherein each bacteriophage has lytic activity against at least five C. perfringens strains which cause necrotic enteritis in poultry.
2. The method of claim 1 , wherein the at least five C. perfringens strains comprise ATCC strain 3624 and ATCC strain 9856.
3. The method of claim 1 , wherein the C. perfringens strains comprise at least five of ATCC strain 25768, ATCC strain 3624, ATCC strain 9856, ATCC strain 3628, ATCC strain 13124, ATCC strain PTA-8495, NRRL strain B-50143, NRRL strain B-50144, NRRL strain B-50145, or a combination thereof.
4. The method of claim 1 , wherein the preparation has lytic activity against ATCC strain 25768, ATCC strain 3624, ATCC strain 9856, ATCC strain 3628, ATCC strain 13124, ATCC strain PTA-8495, NRRL strain B-50143, NRRL strain B-50144, NRRL strain B-50145.
5. The method of claim 4 , wherein the bacteriophage preparation is incapable of infecting at least ten strains of E. coli, L. monocytogenes, S. enterica , and P. aeruginosa.
6. A method of, reducing chicken mortality due to C. perfringens infections comprising administering a purified bacteriophage preparation comprising CPAS-12 (accession number PTA-8479), CPAS-15 (accession number PTA-8480), CPAS-16 (accession number PTA-8481), CPLV-42 (accession number PTA-8483) and CPAS-7 (accession number PTA-8482, wherein each bacteriophage has lytic activity against at least five C. perfringens strains which cause necrotic enteritis in poultry.
7. The method of claim 6 , wherein the at least five C. perfringens strains comprise ATCC strain 3624 and ATCC strain 9856.
8. The method of claim 6 , wherein the C. perfringens strains comprise at least five of ATCC strain 25768, ATCC strain 3624, ATCC strain 9856, ATCC strain 3628, ATCC strain 13124, ATCC strain PTA-8495, NRRL strain B-50143, NRRL strain B-50144, NRRL strain B-50145, or a combination thereof.
9. The method of claim 6 , wherein the preparation has lytic activity against ATCC strain 25768, ATCC strain 3624, ATCC strain 9856, ATCC strain 3628, ATCC strain 13124, ATCC strain PTA-8495, NRRL strain B-50143, NRRL strain B-50144, NRRL strain B-50145.
10. The method of claim 9 , wherein the bacteriophage preparation is incapable of infecting at least ten strains of E. coli, L. monocytogenes, S. enterica , and P. aeruginosa.
11. The method of claim 1 , wherein the bacteriophage preparation lyses greater than or equal to 85% of at least 40 screened C. perfringens strains, and wherein the bacteriophage preparation is incapable of infecting at least ten strains of E. coli, L. monocytogenes, S. enterica , and P. aeruginosa.
12. The method of claim 11 , wherein the bacteriophage preparation lyses greater than or equal to 85% of at least 45 screened C. perfringens strains.
13. The method of claim 12 , wherein each of the individual C. perfringens -specific bacteriophage lyses 15% to 90% of the screened C. perfringens strains.
14. The method of claim 1 , further comprising a pharmaceutically acceptable excipient.
15. The method of claim 14 , wherein the pharmaceutically acceptable excipient is a water-conditioning agent.
16. The method of claim 15 , wherein the water-conditioning agent is a 50 mM citrate-phosphate-thiosulfate buffer comprising about 40 mg sodium thiosulfate, 6.0 gm disodium phosphate (anhydrous), 1.1 gm citric acid (anhydrous) per liter of deionized water, pH 7.0, added at a 1:10 or greater ratio.
17. The method of claim 16 , wherein the administration of the purified bacteriophage preparation comprises administration in water at temperatures of up to 50° C.