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Publication Number
US-12479892-B2
Publication Date
2025-11-25
Expiration Date
Abstract
This invention relates, inter alia, to an immunogenic fragment of a Neisserial Heparin Binding Antigen (NHBA) protein of Neisseria gonorrhoeae (SEQ ID NO: 1) for the prevention and treatment of Neisseria gonorrhoeae or gonococcal- or meningococcal-associated diseases and conditions. In some embodiments, the immunogenic fragment corresponds to a C-terminal fragment of the protein (SEQ ID NO: 2).
Core Innovation
The document relates to Neisserial Heparin Binding Antigen (NHBA) of Neisseria gonorrhoeae, including an immunogenic C-terminal fragment (NHBA-c) represented by SEQ ID NO: 2 and variants thereof. The fragment is between about 165 amino acids to about 200 amino acids in length and comprises, is contained in, consists of or consists essentially of the amino acid sequence set forth in SEQ ID NO: 2 or a variant thereof sharing at least 97% sequence identity with SEQ ID NO: 2. The fragment or variant is presented as an immunogenic protein or antigen for gonococcal disease.
The disclosed antigen format includes fragments, variants, derivatives of SEQ ID NO: 2, and isolated proteins comprising one or a plurality of immunogenic fragments. The scope further includes variants with specified amino acid substitutions at particular residue positions and immunogenic fragments comprising one or more heparin binding residues and/or one or more active site residues. The fragment or variant is linked, conjugated, or otherwise coupled to a carrier protein.
The document also relates to an nhba knockout mutant strain and a complemented strain, and examines recombinant NHBA for glycan binding behavior across many glycan structures. It further summarizes the distribution of NHBA peptide variants in Neisseria gonorrhoeae isolates using the PubMLST database.
Claims Coverage
The document provides four independent claims centered on immunogenic fragments of Neisserial Heparin Binding Antigen (NHBA) from Neisseria gonorrhoeae, including defined length, defined SEQ ID NO: 2 sequence or variants with a minimum sequence identity, and an isolated protein comprising one or a plurality of such fragments. Dependent claim scope further narrows variants and allows carrier conjugation and constraints on heparin-binding and/or active-site residues.
Immunogenic NHBA-c fragment defined by length, SEQ ID NO: 2, and 97% sequence identity
An immunogenic fragment of an isolated Neisserial Heparin Binding Antigen (NHBA) protein of Neisseria gonorrhoeae, between about 165 amino acids to about 200 amino acids in length, comprising, being contained in, consisting of or consisting essentially of an amino acid sequence set forth in SEQ ID NO: 2 or a variant thereof sharing at least 97% sequence identity with SEQ ID NO: 2.
Isolated protein comprising one or a plurality of immunogenic NHBA-c fragments
An isolated protein comprising one or a plurality of immunogenic fragments of an isolated Neisserial Heparin Binding Antigen (NHBA) protein of Neisseria gonorrhoeae, where the immunogenic fragments are between about 165 amino acids to about 200 amino acids in length and comprise, are contained in, consist of or consist essentially of SEQ ID NO: 2 or a variant thereof sharing at least 97% sequence identity with SEQ ID NO: 2.
Fragment comprising heparin binding residues and/or active site residues
The immunogenic fragment comprises one or more heparin binding residues and/or one or more active site residues of the isolated NHBA protein.
Fragment or variant linked or conjugated to a carrier protein
The immunogenic fragment or the variant thereof is conjugated, coupled or otherwise linked to a carrier protein.
Across the independent claims, the core coverage is immunogenic NHBA fragments of SEQ ID NO: 2, or variants, constrained to about 165-200 amino acids and at least 97% sequence identity, including isolated proteins comprising one or more such fragments. Dependent claims refine the covered variants by specifying permitted residue substitutions, tighter sequence-identity thresholds, inclusion of heparin-binding and/or active-site residues, and carrier-conjugated formats.
Stated Advantages
Improved immunogenicity versus full-length NHBA.
Induction of antibodies that promote complement activation, including C3 deposition.
Induction of serum bactericidal activity (SBA).
Induction of opsonophagocytic killing (OPA).
Inhibition of NHBA-heparin interactions.
Reduced adherence to human epithelial cells.
Proposed roles in serum resistance and aggregation/microcolony formation being addressed by the NHBA-c antigen.
Addressing glycan binding, including heparin and chondroitin sulfate, through inhibition of NHBA-glycan interactions.
Documented Applications
A vaccine or therapeutic antigen for gonococcal disease using immunogenic fragments of NHBA from Neisseria gonorrhoeae, and also discussed in connection with Neisseria meningitidis.
Prevention and treatment contexts described in connection with immune response induction using the disclosed NHBA-c antigens.
Detection uses NHBA-binding antibodies, including detecting Neisseria gonorrhoeae and N. meningitidis using anti-NHBA antibodies.
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