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 vaccine for the treatment or prevention of an infection in a mammal comprising:
a detoxified pertussis toxin protein, wherein the detoxified pertussis protein contains a mutation in subunit S1 of B. pertussis;
an enzyme treated pertussis LPS;
and a detoxified pertussis adenylate cyclase protein (P-ACT).
2. The vaccine of claim 1 , wherein the infection is caused by one or more of B. pertussis, B. parapertussis or a serotype or strain of B. pertussis or B. parapertussis.
3. The vaccine of claim 1 , which is protective against infection caused by one or more of B. pertussis, B. parapertussis or a serotype or strain of B. pertussis or B. parapertussis.
4. The vaccine of claim 1 , which is protective against infection caused by multiple serotypes and/or strains of B. pertussis and/or B. parapertussis.
5. The vaccine of claim 1 , wherein the mutation comprises a substitution in S1 of glutamic acid for glycine at amino acid position 129 and a substitution of arginine for lysine at amino acid position 9.
6. The vaccine of claim 1 , wherein enzyme treated LPS comprises LPS treated with one or more alkaline phosphatases or one or more deacylases.
7. The vaccine of claim 6 , wherein the one or more phosphorylaese comprise antarctic phosphatase or lambda protein phosphatase.
8. The vaccine of claim 1 , wherein the detoxified adenylate cyclase protein comprised a dipeptide inserted between amino acids 188 and 189 of native P-ACT.
9. The vaccine of claim 1 , which maintains intrinsic adjuvant activity.
10. The vaccine of claim 1 , further comprising a pharmaceutically acceptable carrier that comprises water, glycerol, alcohol, propylene glycol, fatty alcohols, triglycerides, fatty acid esters, mineral oils, liquid petrolatum, isopropylpalmitate, polyethylene ethanol, polyoxyethylene monolauriater, sodium lauryl sulfate, an anti-oxidant, a humectant, a viscosity stabilizer or modifier, a colorant or a flavoring agent.
11. The vaccine of claim 1 , which produces little to no side effects upon administration to an individual.
12. The vaccine of claim 11 , wherein the little to no side effects comprises an absence of a fever of the mammal attributable a vaccination and/or the absence of an inflammation at the site of administration of the vaccine.
13. The vaccine of claim 1 , which is for administration as an intramuscular injection, an intravenous injection, as an oral administration, as a nasal administration, or as a combination thereof.
14. The vaccine of claim 1 , which contains no adhesins.
15. The vaccine of claim 14 , wherein the adhesins comprise B. pertussis adhesins.
16. The vaccine of claim 1 , which is a liquid, a tablet, a pill or a spray.
17. The vaccine 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.
18. The vaccine of claim 1 , wherein the dose of vaccine per individual is from about 1 μg to 1 mg.
19. The vaccine of claim 1 , wherein the mammal is an adult or a child.