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US-20260124287-A1 - NEISSERIA MENINGITIDIS COMPOSITIONS AND METHODS THEREOF

US20260124287A1US 20260124287 A1US20260124287 A1US 20260124287A1US-20260124287-A1

Abstract

In one aspect, the disclosure relates to a composition including a factor H binding protein (fHBP) and a Neisseria meningitidis non-serogroup B capsular polysaccharide, and methods of use thereof. The disclosure 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.

Inventors

  • Annaliesa Sybil Anderson
  • Shannon Lea Harris
  • John Lance Perez
  • Kathrin Ute Jansen
  • Paul Liberator
  • Cuiwen Tan
  • Thomas Richard Jones
  • Johannes Frederik Beeslaar
  • Judith Absalon
  • Jason Douglas Maguire

Assignees

  • PFIZER INC.

Dates

Publication Date
20260507
Application Date
20250702

Claims (20)

  1. 1 - 39 . (canceled)
  2. 40 . A method of using a kit to induce an immune response to N. meningitidis serogroups A, B, C, W-135 and Y in a human subject aged between 10 to 26 years old, comprising preparing an immunogenic composition by reconstituting a lyophilized composition in a bivalent liquid composition, and administering to the human subject a first dose and a second dose of the immunogenic composition, wherein the second dose is administered to the subject about 6 months after the first dose; wherein the kit comprises: a) the bivalent liquid composition comprises a first purified, lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1; a second purified, lipidated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2; and aluminum; and b) the lyophilized quadrivalent conjugate composition comprises: (i) a purified Neisseria meningitidis serogroup A capsular polysaccharide (MenA) individually conjugated to an adipic acid dihydrazide (ADH) linker by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, wherein the linker is conjugated to tetanus toxoid (TT) by carbodiimide chemistry; (ii) a purified Neisseria meningitidis serogroup C capsular polysaccharide (MenC) individually conjugated to an ADH linker by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, wherein the linker is conjugated to tetanus toxoid (TT) by carbodiimide chemistry; (iii) a purified Neisseria meningitidis serogroup W capsular polysaccharide (MenW) individually conjugated directly to tetanus toxoid (TT) by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, in the absence of a linker; and (iv) a purified Neisseria meningitidis serogroup Y capsular polysaccharide (MenY) individually conjugated directly to tetanus toxoid (TT) by 1-cyano-4-dimethylamino pyridinium tetrafluoroborate, in the absence of a linker; wherein the human subject is naive to vaccination with N. meningitidis serogroups A, C, W-135 and Y capsular polysaccharides; and wherein each dose comprises about 60 μg of the first polypeptide, about 60 μg of the second polypeptide, about 0.25 mg of aluminum, about 5 μg of the MenA capsular saccharide, about 5 μg of the MenC capsular saccharide, about 5 μg of the MenW capsular saccharide, and about 5 μg of the MenY capsular saccharide.
  3. 41 . The method of claim 40 , wherein the kit comprises the bivalent liquid composition contained within a pre-filled syringe (PFS).
  4. 42 . The method of claim 41 , wherein the kit comprises the lyophilized composition contained within a vial.
  5. 43 . The method of claim 42 , wherein the kit comprises a vial adapter.
  6. 44 . The method of claim 43 , wherein the immunogenic composition is prepared by affixing the vial adapter to the vial, attaching the PFS to the vial adapter, transferring the bivalent liquid composition into the vial, reconstituting the lyophilized composition with the bivalent liquid composition, and withdrawing the contents of the vial into the syringe via the vial adapter.
  7. 45 . The method of claim 41 , wherein the kit comprises the PFS stored in a tip cap up orientation.
  8. 46 . The method of claim 41 , wherein the kit comprises the PFS stored in a tip cap horizontal orientation.
  9. 47 . The method of claim 41 , wherein the first dose and the second are about 0.5 mL.
  10. 48 . The method of claim 47 , wherein the PFS has a fill volume between about 0.6 mL and about 0.7 mL.
  11. 49 . The method of claim 40 , wherein the kit comprises MenA polysaccharide conjugated to TT with a mean TT/polysaccharide ratio of 3.
  12. 50 . The method of claim 40 , wherein the kit comprises MenC polysaccharide conjugated to TT with a mean TT/polysaccharide ratio of 3.
  13. 51 . The method of claim 40 , wherein the kit comprises MenY polysaccharide conjugated to TT with a mean TT/polysaccharide ratio of 1.3.
  14. 52 . The method of claim 40 , wherein the kit comprises MenW polysaccharide conjugated to TT with a mean TT/polysaccharide ratio of 1.5.
  15. 53 . The method of claim 40 , wherein the aluminum is aluminum phosphate.
  16. 54 . The method of claim 53 , wherein the immunogenic composition comprises Tris-HCl, sodium chloride, sucrose, histidine, and polysorbate 80.
  17. 55 . The method of claim 40 , wherein the first polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 1.
  18. 56 . The method of claim 40 , wherein the first polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 2.
  19. 57 . The method of claim 40 , wherein between 90% and 100% of the amount of the first polypeptide is bound to the aluminum for 24 hours and between 90% and 100% of the amount of the second polypeptide is bound to the aluminum for 24 hours.
  20. 58 . The method of claim 40 , wherein the immunogenic composition does not comprise diphtheria toxoid or CRM.

Description

CROSS REFERENCE TO RELATED APPLICATIONS The present application claims the benefit of U.S. Provisional Patent Application 62/907,097, filed Sep. 27, 2019, and U.S. Provisional Patent Application 63/040,498, filed Jun. 17, 2020. All of the foregoing applications are hereby incorporated by reference in their entireties. REFERENCE TO SEQUENCE LISTING This application is being filed electronically via EFS-Web and includes an electronically submitted sequence listing in .xml format. The .xml file contains a sequence listing entitled “PC072522B Sequence Listing.xml” created on Jun. 24, 2025 and having a size of 102,400 bytes. The sequence listing contained in this .xml file is part of the specification and is incorporated herein by reference in its entirety. FIELD OF THE DISCLOSURE The present disclosure relates to Neisseria meningitidis compositions and methods thereof. BACKGROUND OF THE DISCLOSURE Neisseria meningitidis is a Gram-negative encapsulated bacterium that can cause sepsis, meningitis, and death. N. meningitidis can be classified into at least 12 serogroups (including serogroups A, B, C, 29E, H, I, K, L, W-135 (mostly now referred to as W), X, Y and Z) based on chemically and antigenically distinctive polysaccharide capsules. Strains with five of the serogroups (A, B, C, Y, and W135) are responsible for the majority of disease. Meningococcal meningitis is a devastating disease that can kill children and young adults within hours despite the availability of antibiotics. There is a need for improved immunogenic compositions against meningococcal serogroups A, B, C, Y, and W135 and/or X. Currently, a cross-protective vaccine or composition effective against a wide range of MnB and meningococcal serogroups A, C, Y, and W and/or X isolates is not yet commercially available. Accordingly, a cross-protective vaccine or composition effective against diverse MnB and meningococcal serogroups A, C, Y, and W and/or X isolates is needed. It is a further object of the disclosure to provide improved schedules for administering a meningococcal vaccine. Under the current recommendation scheme, there are four to five vaccinations given against meningococcal serogroups A, C, W, Y and B, given at different ages. There is an unmet need for efficient vaccinations that may to simplify immunization schedules and improve vaccination coverage to achieve further reductions in invasive meningococcal disease (IMD). SUMMARY OF THE DISCLOSURE To meet these and other needs, the present disclosure relates to Neisseria meningitidis compositions and methods thereof. The inventors discovered a method of inducing an immune response in a human, including administering to the human a composition comprising a) a polypeptide derived from a Neisseria meningitidis factor H binding protein (fHBP); (b) a Neisseria meningitidis serogroup A capsular saccharide conjugate; (c) a Neisseria meningitidis serogroup C capsular saccharide conjugate; (d) a Neisseria meningitidis serogroup W capsular saccharide conjugate; and (e) a Neisseria meningitidis serogroup Y capsular saccharide conjugate, wherein the composition induces an immune response to at least one of N. meningitidis serogroups A, C, W-135 and Y capsular polysaccharides and N. meningitidis serogroup B, wherein the immune response includes a titer of serum bactericidal antibodies that is higher than a titer of serum bactericidal antibodies induced by a respective licensed vaccine against the serogroup. The inventors surprisingly discovered a method of inducing an immune response in a human, including administering to the human a composition comprising a) a first polypeptide derived from a Neisseria meningitidis factor H binding protein (fHBP); (b) a second polypeptide derived from a Neisseria meningitidis factor H binding protein (fHBP); (c) a Neisseria meningitidis serogroup A capsular saccharide conjugate; (d) a Neisseria meningitidis serogroup C capsular saccharide conjugate; (e) a Neisseria meningitidis serogroup W capsular saccharide conjugate; and (f) a Neisseria meningitidis serogroup Y capsular saccharide conjugate, wherein the composition induces an immune response to at least one of N. meningitidis serogroups A, C, W-135 and Y capsular polysaccharides and N. meningitidis serogroup B, wherein the immune response includes a titer of serum bactericidal antibodies that is higher than a titer of serum bactericidal antibodies induced by a respective licensed vaccine against the serogroup. In some embodiments, the polypeptide includes an amino acid sequence having at least 70% identity to any one amino acid sequence selected from SEQ ID NO: 1 to SEQ ID NO: 62. In a preferred embodiment, the composition includes (a) a first polypeptide including the amino acid sequence set forth in SEQ ID NO: 1; (b) a second polypeptide including the amino acid sequence set forth in SEQ ID NO: 2; (c) a Neisseria meningitidis serogroup A capsular saccharide conjugated to an adipic acid dihydrazide (ADH) linker