JPWO2020117618A5 - - Google Patents

Claims (29)

An acellular pertussis (aP) booster vaccine comprising tetanus toxoid, diphtheria toxoid, detoxified pertussis toxin, filamentous hemagglutinin, pertactin, pilus types 2 and 3, at least one Toll-like receptor (TLR) an agonist and an aluminum salt, wherein the at least one TLR agonist is formulated with the aluminum salt;
said aP booster vaccine. 2. The aP booster vaccine of claim 1, wherein the TLR agonist is a TLR4 agonist and/or a TLR9 agonist. 3. The aP booster vaccine of Claim 2, wherein the TLR4 agonist comprises E6020. 3. The aP booster vaccine of Claim 2, wherein the TLR9 agonist comprises CpG1018. The aP booster vaccine of any one of claims 1-4, wherein the tetanus toxoid is present in an amount of 8-12 Lf/mL, optionally 9-11 Lf/mL or 10 Lf/mL. The aP booster vaccine of any one of claims 1-4, wherein the diphtheria toxoid is present in an amount of 3-8 Lf/mL, optionally 3-6 Lf/mL or 4-5 Lf/mL. 5. Any one of claims 1-4, wherein the detoxified pertussis toxin is genetically detoxified pertussis toxin and is present in an amount of 16-24 μg/mL, optionally 18-22 μg/mL or 20 μg/mL. aP booster vaccine according to paragraph. Filamentous hemagglutinin is 5-15 μg/mL, optionally 8-12 μg/mL or 1
The aP booster vaccine of any one of claims 1-4, present in an amount of 0 μg/mL. The aP booster vaccine of any one of claims 1-4, wherein pertactin is present in an amount of 5-15 μg/mL, optionally 8-12 μg/mL or 10 μg/mL. The aP booster vaccine of any one of claims 1-4, wherein pilus types 2 and 3 are present in an amount of 10-20 μg/mL, optionally 14-16 μg/mL or 15 μg/mL. The aP booster vaccine of any one of claims 2-4, wherein the TLR4 agonist is present in an amount of 10 μg/mL or less, optionally 0.5-5 μg/mL or 2 μg/mL or less. The aP booster vaccine of any one of claims 2-4, wherein the TLR9 agonist is present in an amount of 250-750 μg/mL, optionally 400-600 μg/mL or 500 μg/mL. The aP booster vaccine of any one of claims 1-4, further comprising Tris-buffered saline. The aP booster vaccine of any one of claims 1-4, having an aluminum concentration of 0.5-0.75 mg/mL, optionally 0.66 mg/mL. The aP booster vaccine of any one of claims 1-4, wherein at least one of tetanus toxoid, diphtheria toxoid, and genetically detoxified pertussis toxin is adsorbed to an aluminum salt. The aP booster vaccine of any one of claims 1-4, wherein the aluminum salt is aluminum hydroxide or aluminum phosphate. Tetanus toxoid present in an amount of 9-11 Lf/mL, optionally 8-12 Lf/mL, diphtheria toxoid present in an amount of 3-8 Lf/mL, optionally 3-5 Lf/mL, detoxified pertussis The toxin is genetically detoxified pertussis toxin, present in an amount of 16-24 μg/mL, optionally 18-22 μg/mL, and filamentous hemagglutinin, 5-15 μg/mL, optionally 8-10 μg/mL. present in an amount of 12 μg/mL, pertactin is present in an amount of 5-15 μg/mL, optionally 8-12 μg/mL, and pilus types 2 and 3 are present in an amount of 10-20 μg/mL, optionally 14-16 μg /mL, the aluminum salt is aluminum hydroxide and is present in a concentration of 0.25-0.75 mg/mL, optionally 0.6-0.7 mg/mL, and the TLR agonist is TLR4 The aP booster vaccine according to any one of claims 1-4, which is an agonist and/or a TLR9 agonist. 18. The aP booster vaccine of claim 17, wherein the TLR4 agonist comprises E6020 and is present in an amount of 2 μg/mL or less or the TLR9 agonist comprises CpG1018 and is present in an amount of 400-600 μg/mL. Tetanus toxoid is present in an amount of 10 Lf/mL, diphtheria toxoid is present in an amount of 4-5 Lf/mL, detoxified pertussis toxin is genetically detoxified pertussis toxin, and is present in an amount of 20 μg/mL. filamentous hemagglutinin is present in an amount of 10 μg/mL, pertactin is present in an amount of 10 μg/mL, pilus types 2 and 3 are present in an amount of 15 μg/mL, 19. The aP booster vaccine of claim 18, wherein the aluminum salt is aluminum hydroxide and is present at a concentration of 0.66 mg/mL and the TLR agonist is a TLR4 agonist and/or a TLR9 agonist. 20. The aP booster vaccine of claim 19, wherein the TLR4 agonist comprises E6020 and is present in an amount of 0.5-5 μg/mL or the TLR9 agonist comprises CpG1018 and is present in an amount of 500 μg/mL. In a 0.5 mL unit dosage form for administration to human subjects, tetanus toxoid was present in an amount of 5 Lf and diphtheria toxoid was present in an amount of 2-2.5 Lf and was genetically detoxified. Pertussis toxin is present in an amount of 10 μg, filamentous hemagglutinin is present in an amount of 5 μg, pertactin is present in an amount of 5 μg, pilus types 2 and 3 are present in an amount of 7.5 μg/mL. and the aluminum hydroxide is present in a concentration of 0.33 mg, E6020 is present in an amount of 0.25-2.5 μg, or CpG1018 is present in an amount of 250 μg. aP booster vaccine. 5. The aP booster vaccine of any one of claims 1-4, wherein the detoxified pertussis toxin is genetically detoxified pertussis toxin and comprises the R9K and E129G mutations. The aP booster vaccine of any one of claims 1-4, further comprising a Haemophilus influenzae type b glycoconjugate, a hepatitis B virus surface antigen, and/or an inactivated poliovirus. 5. The aP booster vaccine of any one of claims 1-4 for inducing an immune response in a human subject previously exposed to a Bordetella pertussis antigen, wherein the previous exposure to the Bordetella pertussis antigen comprises: Inducing a Th2-dominant immune response in said human subject, wherein said aP booster vaccine redirects said Th2-dominant immune response to a Th1-dominant immune response or a Th1/Th17-dominant immune response in said human subject. The aP booster vaccine, which is formulated in The human subject has received an acellular pertussis (aP) priming vaccine prior to inducing an immune response in the human subject, the aP priming vaccine formulated to induce a Th2-dominant immune response in the human subject. 25. The aP booster vaccine of claim 24, wherein the aP booster vaccine is 26. The aP booster vaccine of claim 24 or 25, wherein the human subject is 4 years of age or older. 26. The aP booster vaccine of claim 24 or 25, wherein the human subject is 10 years of age or older. Th1-dominant immune responses are associated with decreased IL-5 protection or lower IgG1/IgG2a ratios when compared to Th2-dominant immune responses induced by aP priming or aP booster vaccines containing no TLR agonists. A Th1/Th17-dominant response is characterized by one or more of the levels of IL-17 protection when compared to a Th2-dominant immune response induced by an aP priming or aP booster vaccine that does not contain a TLR agonist. 26. The aP booster vaccine of claim 24 or 25, characterized by one or more of increased and decreased IL-5 protection or a lower IgG1/IgG2a ratio. 26. The aP booster vaccine of claim 25, wherein the aP priming vaccine comprises tetanus toxoid, diphtheria toxoid, pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, but does not contain a TLR agonist. .