Adenylate cyclase deficient bordetella strains
View Patent ↗A CyaA-deficient B. pertussis mutant was constructed and used in a vaccine. The pertussis-specific antibody profile and Th17 response induced by vaccination with the mutant was surprisingly comparable to that induced by B. pertussis strains not deficient in CyaA.
1. A vaccine comprising a pharmaceutically acceptable carrier and a live attenuated Bordetella strain that has been rendered deficient in functional adenylate cyclase toxin (CyaA), functional pertussis toxin (PTX), functional dermonecrotic toxin (DNT), and functional tracheal cytotoxin (TCT), but retains the ability to colonize a mammalian subject's lungs and induce a protective immune response against Bordetella infection, wherein the genes encoding CyaA, PTX, and AmpG have been deleted, mutated or replaced.
2. The vaccine of claim 1 , wherein the strain comprises a gene encoding CyaA which has been mutated such that the strain fails to produce CyaA.
3. The vaccine of claim 1 , wherein the strain comprising a gene encoding PTX which has been mutated such that the strain fails to produce functional PTX.
4. The vaccine of claim 1 , wherein the strain lacks a gene encoding functional DNT.
5. The vaccine of claim 1 , wherein the strain lacks a functional wild-type ampG gene.
6. The vaccine of claim 5 , wherein the strain comprises a heterologous ampG gene.
7. The vaccine of claim 1 , wherein the strain comprises: a gene encoding CyaA which has been mutated such that the strain fails to produce functional CyaA and a gene encoding PTX which has been mutated such that the strain fails to produce functional PTX; and lacks a gene encoding functional DNT and a functional wild-type ampG gene.
8. The vaccine of claim 1 , wherein the strain is BPAL10.
9. The vaccine of claim 1 , wherein the vaccine is provided in a single dosage form which comprises at least 5×10 5 colony forming units (CFU) of the strain.
10. The Bordetella strain designated BPAL10.