Bordetella pertussis immunogenic vaccine compositions
This invention is directed to composition, vaccines, tools and methods in the treatment and prevention of Bordetella pertussis . In particular, the invention is directed to a three-pronged approach that involves removal of the nonessential vaccine components, use of a nondenatured, genetically detoxified mutant, and adding virulence factors.
1. A method of manufacturing an immunogenic composition comprising a detoxified pertussis toxin, a detoxified pertussis adenylate cyclase toxin, a Toll-like receptor agonist and an immunogenic oligosaccharide or fragment thereof, wherein the method comprises:
detoxifying a pertussis toxin obtained from E. coli, B. bronchiseptica , or B pertussis forming the detoxified pertussis toxin;
detoxifying a pertussis adenylate cyclase toxin containing the amino acid sequence of SEQ ID NO 1 obtained from E. coli, B. bronchiseptica , or B pertussis forming the detoxified pertussis adenylate cyclase;
combining the detoxified pertussis toxin and the detoxified pertussis adenylate cyclase with the Toll-like receptor agonist and the immunogenic oligosaccharide or fragment thereof, obtained or derived from a lipooligosaccharide of B pertussis , wherein the immunogenic oligosaccharide or fragment thereof is conjugated to a carrier protein or peptide; and
forming the immunogenic composition.
2. The method of claim 1 , wherein the pertussis toxin is detoxified genetically.
3. The method of claim 1 , wherein the pertussis adenylate cyclase is detoxified genetically.
4. The method of claim 1 , wherein the immunogenic oligosaccharide or fragment thereof comprises one or more of the oligosaccharides of the structure of: a dodecasaccharide core of B. bronseptica lipooligosaccharide, or a pentasaccharide hapten obtained by deamination of the lipooligosaccharide of B. pertussis strain 186.
5. The method of claim 1 , wherein the lipooligosaccharide of B pertussis comprises a lipid A, a core oligosaccharide, and a distal trisaccharide.
6. The method of claim 5 , wherein the distal trisaccharide comprises heptose or anhydromannose.
7. The method of claim 1 , wherein the lipooligosaccharide of B pertussis comprises a spacer and a terminal aldehyde.
8. The method of claim 1 , wherein the lipooligosaccharide of B pertussis comprises a synthetic B pertussis epitope.
9. The method of claim 8 , wherein immunogenic oligosaccharide or fragment thereof comprises a spacer and a terminal aldehyde distal to the epitope of B pertussis.
10. The method of claim 1 , wherein the lipooligosaccharide of B pertussis is devoid of a terminal trisaccharide.
11. The method of claim 1 , wherein the immunogenic oligosaccharide or fragment thereof comprises the formula:
12. The method of claim 1 , wherein the immunogenic igosaccharide or fragment thereof comprises the formula:
13. The method of claim 1 , wherein the immunogenic oligosaccharide or fragment thereof comprises the formula: α-GlcNAc-4β-ManNAc3NAcA-3-β-FucNAc4NMe-1-linker-R; wherein R═-CH═O; —COOH or —CH2-SH.
14. The method of claim 1 , wherein the lipooligosaccharide comprises a synthetic or a deamination product obtained or derived from B. pertussis.
15. The method of claim 1 , wherein the detoxified pertussis toxin and the immunogenic oligosaccharide or fragment thereof are obtained or derived from B pertussis.
16. The method of claim 1 , wherein the Toll-like receptor agonist comprises TLR-2, TLR-4 or TLR-8.
17. The method of claim 1 , wherein the immunogenic composition is aqueous.
18. The method of claim 1 , wherein the immunogenic composition is lyophilized.
19. The method of claim 1 , wherein the lyophilized immunogenic composition is suspended in a liquid prior to use.