Attenuated Bordetella strains
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. An immunogenic composition comprising a pharmaceutically acceptable carrier and a dose of a live attenuated Bordetella pertussis strain which is able to colonize a subject when administered to the subject, wherein the live attenuated Bordetella pertussis strain has its native Bordetella pertussis ampG gene replaced with a heterologous ampG gene wherein the replacement of the Bordetella pertussis ampG gene with the heterologous ampG gene causes the Bordetella pertussis strain to express less than 5% of the tracheal cytotoxin (TCT) activity as that expressed by a Bordetella pertussis strain which does not have its native Bordetella pertussis ampG gene replaced with the heterologous ampG gene.
2. The immunogenic composition of claim 1 , wherein the live attenuated Bordetella pertussis strain comprises a heterologous expression platform which carries a heterologous antigen.
3. The immunogenic composition of claim 2 , wherein the heterologous antigen is one expressed by a respiratory pathogen selected from the group consisting of: Neisseria, Pneumophila, Yersinia, Pseudomonas, Mycobacteria , and Influenza.
4. The immunogenic composition of claim 1 , wherein the immunogenic composition is formulated as a powder.
5. The immunogenic composition of claim 1 , wherein the immunogenic composition is formulated as a liquid.
6. The immunogenic composition of claim 1 , wherein the immunogenic composition is formulated as a gel.