Prevention of pertussis using 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) and functional pertussis toxin (PTX), 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, and PTX 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.
8. The vaccine of claim 1 , wherein the vaccine is provided in a single dosage form which comprises at least 1×10 6 colony forming units (CFU) of the strain.
9. The vaccine of claim 1 , wherein the vaccine is provided in a single dosage form which comprises at least 5×10 6 CFU of the strain.
10. The vaccine of claim 1 , wherein the vaccine is provided in a single dosage form which comprises at least 1×10 7 CFU of the strain.