Patent
In one aspect, the invention relates to a composition including a factor H binding protein (fHBP) and a Neisseria meningitidis non-serogroup B capsular polysaccharide. The invention further relates to uses of a composition that includes fHBP, such as, for example, uses to elicit an immune response against N. meningitidis serogroup B strains and non-serogroup B strains. The compositions and methods described herein are directed to administration in humans, including adults, adolescents, toddlers, and infants.
1. A method of inducing an immune response against a Neisseria meningitidis serogroup A strain expressing B16 factor H binding protein in a human comprising mixing (a) a composition comprising (i) a first lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1; (ii) a second lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2; (iii) a Neisseria meningitidis serogroup A (MenA) capsular saccharide conjugated to an adipic acid dihydrazide (ADH) linker, wherein the linker is conjugated to tetanus toxoid (TT); (iv) a Neisseria meningitidis serogroup C (MenC) capsular saccharide conjugated to an ADH linker, wherein the linker is conjugated to tetanus toxoid (TT); (v) a Neisseria meningitidis serogroup W135 (MenW) capsular saccharide conjugated to tetanus toxoid (TT) (MenW-TT conjugate); and (vi) a Neisseria meningitidis serogroup Y (MenY) capsular saccharide directly conjugated to tetanus toxoid (TT) (MenY-TT conjugate); and (b) administering an effective amount of the composition to the human, wherein the composition comprises about 5 μg of the MenA capsular saccharide conjugated to about 7.5 μg of the TT; about 5 μg of the MenC capsular saccharide conjugated to about 7.5 μg of the TT; about 5 μg of the MenW capsular saccharide conjugated to about 3.75 μg of the TT; and about 5 μg of the MenY capsular saccharide conjugated to about 3.25 μg of the TT per dose; and further comprises aluminum.
2. The method according to claim 1 , wherein at least 90% of the total composition of the first polypeptide is bound to the aluminum in the composition.
3. The method according to claim 1 , wherein at least 90% of the total composition of the second polypeptide is bound to the aluminum in the composition.
4. The method according to claim 1 , wherein the composition further comprises polysorbate-80.
5. The method according to claim 1 , wherein the composition further comprises sucrose.
6. The method according to claim 1 , wherein the composition further comprises histidine.
7. The method according to claim 1 , wherein the composition comprises about 120 μg/ml of the first polypeptide; about 120 μg/ml of the second polypeptide; about 0.5 mg/ml of the aluminum as aluminum phosphate; about 0.02 mg polysorbate-80; about 10 mM histidine; and about 150 mM sodium chloride.
8. The method of claim 1 , wherein the composition comprises about 60 μg of the first polypeptide; about 60 μg of the second polypeptide; about 5 μg of the MenA capsular saccharide conjugated to about 7.5 μg of the TT; about 5 μg of the MenC capsular saccharide conjugated to about 7.5 μg of the TT; about 5 μg of the MenW capsular saccharide conjugated to about 3.75 μg of the TT; and about 5 μg of the MenY capsular saccharide conjugated to about 3.25 μg of the TT per dose; about 97 μg of Tris-HCl, pH 6.8±0.3; 4.69-4.71 mg of sodium chloride; about 28 mg of sucrose; about 0.78 mg of L-Histidine; about 0.02 mg polysorbate-80; about 0.25 mg of the aluminum; and further comprising 0.5 mL water, per dose.
9. The method according to claim 1 , wherein the first polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 1.
10. The method according to claim 1 , wherein the second polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 2.
11. The method according to claim 1 , wherein the composition does not comprise a hybrid protein.
12. The method according to claim 1 , wherein the composition does not comprise a fusion protein.
13. The method according to claim 1 , wherein the composition is not lyophilized.
14. The method according to claim 1 , wherein the composition does not comprise formaldehyde.
15. The method according to claim 1 , wherein the composition does not comprise diphtheria toxoid or CRM.
16. The method according to claim 1 , wherein the human is aged less than 12 months.
17. The method according to claim 1 , wherein the human is aged 12 months to 18 months.
18. The method according to claim 1 , wherein the human is aged 18 months to 24 months.
19. The method according to claim 1 , wherein the human is aged 24 months to 10 years.
20. The method according to claim 1 , wherein the human is aged at least 10 years.
21. The method according to claim 1 , wherein the human is aged 10 to 25 years.