A mutated Bordetella strain comprising at least a mutated ptx gene, a deleted or mutated dnt gene and a heterologous ampG gene is provided. The attenuated mutated Bordetella strain can be used in an immunogenic composition or a vaccine for the treatment or prevention of a Bordetella infection. Use of the attenuated Bordetella strain for the manufacture of a vaccine or immunogenic composition, as well as methods for protecting mammals against infection by Bordetella are also provided.
1. A live attenuated Bordetella pertussis strain comprising at least a mutated pertussis toxin (ptx) gene, a deleted or mutated dermonecrotic toxin (dnt) gene, and a heterologous ampG gene replacing the Bordetella ampG gene, wherein the strain is able to colonize and induce protective immunity against Bordetella pertussis infection in a subject when administered to the subject.
2. The live attenuated Bordetella pertussis strain of claim 1 , wherein the live attenuated Bordetella strain expresses less than 5% residual tracheal cytotoxin (TCT) activity.
3. An immunogenic composition comprising a dose of the live attenuated Bordetella pertussis strain of claim 1 and a pharmaceutically acceptable carrier.
4. The immunogenic composition of claim 3 , wherein the dose consists of 1×10 3 to 1×10 6 of the live attenuated Bordetella pertussis strain bacteria.
5. The immunogenic composition of claim 3 , wherein the dose consists of 1×10 4 to 5×10 6 of the live attenuated Bordetella pertussis strain bacteria.
6. The immunogenic composition of claim 3 , wherein the dose of the live attenuated Bordetella pertussis strain and the pharmaceutically acceptable carrier are comprised within a spray bottle or nasal inhaler.
7. The immunogenic composition of claim 3 , wherein the dose of the live attenuated Bordetella pertussis strain and the pharmaceutically acceptable carrier are formulated as a dry powder.
8. The immunogenic composition of claim 3 , wherein the dose of the live attenuated Bordetella pertussis strain and the pharmaceutically acceptable carrier are comprised within an aerosolized liquid.