Bordetella vaccine
View Patent ↗The present invention provides genetically engineered strains of the Bordetella species to include one or more mutations preventing expression of the gene encoding the Bordetella Sigma Regulator (also referred to as “bsr,” “btrS,” and “brpL”), compositions and vaccines thereof, and the use of such engineered strains in methods to protect against Bordetella spp, including but not limited to Bordetella bronchiseptica, B. pertussis, B. parapertussis, B. homelsii , or B. avium . In some aspects, the present invention provides the Bordetella bronchiseptica strain RB50Δbsr, compositions and vaccines thereof, and the use of Bordetella bronchiseptica strain RB50Δfer in methods to protect against Bordetella spp, including but not limited to Bordetella bronchiseptica, B. pertussis, B. parapertussis, B. homelsii , or B. avium.
1. A vaccine composition effective for inducing sterilizing immunity against Bordetella bronchiseptica, Bordetella pertussis , or Bordetella parapertussis in a vertebrate subject, the vaccine composition comprising an effective amount of an isolated strain of a Bordetella species and a pharmaceutically acceptable carrier suitable for administration to a vertebrate subject,
wherein the isolated strain of the Bordetella species consists of a single mutation,
wherein the single mutation prevents expression of the bsr sigma factor (also known as the btrS gene product or the brpL gene product),
wherein the Bordetella species is selected from Bordetella bronchiseptica, Bordetella pertussis , or Bordetella parapertussis , and
wherein sterilizing immunity prevents colonization in the lung and/or nasal cavity of the subject and prevents further transmission.
2. The vaccine composition of claim 1 , wherein the vaccine composition is formulated for intranasal, oral, intradermal, or intramuscular administration to the vertebrate subject.
3. The vaccine composition of claim 1 , wherein the sterilizing immunity comprises cross-protective immunity against a different Bordetella species selected from Bordetella bronchiseptica, Bordetella pertussis , or Bordetella parapertussis.
4. A vaccine composition effective for inducing sterilizing immunity against Bordetella bronchiseptica, Bordetella pertussis , or Bordetella parapertussis in a vertebrate subject, the vaccine composition comprising an effective amount of an isolated strain of a Bordetella species and a pharmaceutically acceptable carrier suitable for administration to a vertebrate subject,
wherein the isolated strain of the Bordetella species comprises a mutation preventing expression of the bsr sigma factor (also known as the btrS gene product or the brpL gene product) and does not comprise a mutation in a gene of the adenylate cyclase toxin (CyaA) locus,
wherein the Bordetella species is selected from Bordetella bronchiseptica, Bordetella pertussis , or Bordetella parapertussis , and
wherein sterilizing immunity prevents colonization in the lung and/or nasal cavity of the subject and prevents further transmission.
5. The vaccine composition of claim 4 , wherein the mutation comprises an in frame deletion of the gene encoding the bsr sigma factor.
6. The vaccine composition of claim 4 , wherein the Bordetella species comprises Bordetella bronchiseptica strain RB50.
7. The vaccine composition of claim 4 , wherein the vaccine composition is formulated for intranasal, oral, intradermal, or intramuscular administration to the vertebrate subject.
8. The vaccine composition of claim 4 , wherein the sterilizing immunity comprises cross-protective immunity against a different Bordetella species selected from Bordetella bronchiseptica, Bordetella pertussis , or Bordetella parapertussis.
9. A method of vaccinating a subject against Bordetella bronchiseptica, B. pertussis , or B. parapertussis , the method comprising administering the vaccine composition of claim 4 to the subject.
10. The vaccine composition of claim 1 , wherein the mutation comprises an in frame deletion of the gene encoding the bsr sigma factor.
11. The vaccine composition of claim 1 , wherein the Bordetella species comprises Bordetella bronchiseptica strain RB50.
12. The vaccine composition of claim 1 , wherein the Bordetella species comprises Bordetella bronchiseptica and the mutation comprises an in frame deletion of the gene encoding the bsr sigma factor.
13. The vaccine composition of claim 12 , wherein the isolated Bordetella species comprises the Bordetella bronchiseptica RB50 strain.
14. A method of vaccinating a subject against Bordetella bronchiseptica, B. pertussis , or B. parapertussis , the method comprising administering the vaccine composition of claim 1 to the subject.
15. The method of claim 14 , comprising intranasal, oral, intradermal, or intramuscular administration.
16. The method of claim 14 , wherein the subject is livestock or domestic pet.
17. The method of claim 16 , wherein the subject is a cow, pig, chicken, dog, cat, sheep, or horse.
18. The method of claim 14 , wherein the subject is a human.