Vaccine for prophylaxis or treatment of an allergen-driven airway pathology
View Patent ↗The present invention relates to a live attenuated Bordetella pertussis vaccine which is deficient for tracheal cytotoxin (TCT), pertussis toxin (PTX), and dermonecrotic toxin (DNT) for prophylaxis or treatment of an allergen-driven airway pathology.
1. A method for preventing or reducing chronic airway inflammation induced in response to exposure to an allergen which induces a Th2 response in a subject, the method comprising the step of infecting the subject's respiratory tract with a live Bordetella pertussis strain which is deficient for tracheal cytotoxin (TCT), pertussis toxin (PTX), and dermonecrotic toxin (DNT), wherein the step of infecting the subject's respiratory tract results in the subject developing a Th1 immune response which prevents or reduces the development of chronic airway inflammation induced in response to exposure to the allergen.
2. The method of claim 1 , wherein the strain comprises a mutated pertussis toxin (ptx) gene, a deleted or mutated dermonecrotic (dnt) gene, and a heterologous ampG gene.
3. The method of claim 2 , wherein the heterologous ampG gene is an E. coli ampG gene that replaces the wild-type Bordetella strain ampG gene.
4. The method of claim 2 , wherein the mutation of the ptx gene comprises the substitution of an amino acid involved in substrate binding and/or an amino acid involved in catalysis.
5. The method of claim 4 , wherein the substitution of the amino acid involved in substrate binding comprises R9K and the substitution of the amino acid involved in catalysis comprises E129G.
6. The method of claim 2 , wherein the heterologous ampG gene is the only heterologous gene in the strain.