Manipulation of gene copy number in bordetella

摘要

A protein expression levels from Bordetella strains, particularly Bordetella pertussis, are altered by genetic modification to a natural Bordetella strain whereby one or more of the natural genes, particularly including the TOX, FHA, CYA and PRN genes, is deleted from the genome of the natural strain and one or more of the natural genes or a genetic mutation thereof, particularly a genetically-detoxified TOX* gene, or a hybrid gene, is inserted into the genome of the natural strain to provide at least two copies of one or more of the natural genes or genetic mutation thereof or hybrid gene, singly or in tandem. The altered genotype Bordetella strain is useful in producing whole-cell or defined component vaccines against Bordetella, particularly whooping cough, which may be employed in combination with other vaccines.