Genetically detoxified pertussis vaccine that maintains intrinsic adjuvant activity
The invention is directed to a method for the production of a pertussis vaccine and, in particular, a detoxified pertussis vaccine comprising detoxified pertussis toxin (PT), detoxified pertussis lipopolysaccharide (P-LPS), and detoxified pertussis adenylate cyclase toxin (P-ACT). The invention is also directed to the manufacture of a vaccine or the invention and methods for the administration of a detoxified vaccine to patients.
1. A method of treating or preventing an infection caused by one or more of B. pertussis, B. parapertussis or a serotype or strain of B. pertussis or B. parapertussis , in a mammal comprising administering to the mammal a therapeutically effective dose of a vaccine, wherein the vaccine comprises a detoxified pertussis toxin protein; an enzyme treated pertussis detoxified LPS; and a detoxified pertussis adenylate cyclase protein.
2. The method of claim 1 , wherein administering is via injection, intramuscular injection, intravenous injection, oral administration, nasal administration, or a combination thereof.
3. The method of claim 1 , wherein the vaccine is a liquid, a tablet, a pill or a spray.
4. The method of claim 1 , wherein the therapeutically effective dose is an amount of vaccine which produces an immune response in the mammal that is protective against and/or treats the infection.
5. The method of claim 4 , wherein the amount of vaccine is from about 1 μg to 1 mg per dose.
6. The method of claim 1 , wherein the therapeutically effective dose is a single dose.
7. The method of claim 1 , wherein administration of the vaccine to the mammal produces no side effects.
8. The method of claim 7 , wherein the no side effects comprise the absence of a fever or an inflammation at the site of administration.
9. The method of claim 1 , wherein the vaccine is protective against and/or treats an infection caused by multiple serotypes and/or strains of B. pertussis and/or B. parapertussis.
10. The method of claim 1 , wherein the detoxified pertussis protein contains a mutation in one or more of subunits S 1 -S 5 of B. pertussis.
11. The method of claim 10 , wherein the mutation comprises a substitution in S 1 of glutamic acid for glycine at amino acid position 129 and a substitution of arginine for lysine at amino acid position 9 .
12. The method of claim 1 , wherein enzyme treated LPS comprises LPS treated with one or more alkaline phosphatases or one or more deacylases.
13. The method of claim 12 , wherein the one or more phosphorylaese comprise Antarctic phosphatase or lambda protein phosphatase.
14. The method of claim 1 , wherein the detoxified adenylate cyclase protein comprised a dipeptide inserted between amino acids 188 and 189 of native pertussis adenylate cyclase protein.
15. A method of treating or preventing infections caused by multiple strains and/or serotypes of B. pertussis and B. parapertussis in a mammal comprising administering to the mammal a therapeutically effective dose of a vaccine, wherein the vaccine comprises a detoxified pertussis toxin protein wherein the detoxified pertussis protein contains a mutation in one or more of subunits S 1 -S 5 of B. pertussis ; a pertussis detoxified LPS that has been treated with one or more alkaline phosphatases or one or more deacylases; and a detoxified pertussis adenylate cyclase protein that contains one or more mutations.
16. The method of claim 15 , wherein the one or more phosphorylaese comprise Antarctic phosphatase or lambda protein phosphatase.
17. The method of claim 15 , wherein the mutation comprises a substitution in S 1 of glutamic acid for glycine at amino acid position 129 and a substitution of arginine for lysine at amino acid position 9 .
18. The method of claim 1 , wherein the detoxified adenylate cyclase protein comprised a dipeptide inserted between amino acids 188 and 189 of native pertussis adenylate cyclase protein.