Periodontitis vaccine and related compositions and methods of use
Inventors
Assignees
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Publication Number
US-12121575-B2
Publication Date
2024-10-22
Expiration Date
Abstract
An immunogenic composition, a periodontal vaccine formulation containing the immunogenic composition, and methods for treating or preventing periodontal disease are provided, where the methods involves administering an immunologically effective amount of the composition or vaccine formulation to a subject. The immunogenic composition contains at least one polypeptide that comprises: an Mfa1 antigen sequence that is substantially homologous to an immunogenic amino acid sequence from an Mfa1 fimbrilin protein of a Porphyromonas bacterium; and an HA1 antigen sequence, an HA2 antigen sequence, or both an HA1 antigen sequence and an HA2 antigen sequence, wherein the HAI antigen sequence is substantially homologous to an immunogenic amino acid sequence from an RgpA Gingipain hemagglutinin domain 1 contained within an RgpA Gingipain protein of a Porphyromonas bacterium, and the HA2 antigen sequence is substantially homologous to an immunogenic amino acid sequence from an RgpA Gingipain hemagglutinin domain 2 contained within an RgpA Gingipain protein of a Porphyromonas bacterium.
Core Innovation
The invention relates to a periodontitis vaccine that comprises immunogenic polypeptides targeting Porphyromonas virulence factors. The composition includes an Mfa1 antigen sequence and HA1 and/or HA2 antigen sequences, wherein the antigen sequences are substantially homologous to defined regions of Mfa1 fimbrilin and RgpA gingipain hemagglutinin domains 1 and 2.
In one aspect, the antigen sequences and domains are provided as fusion proteins or as separate recombinant polypeptides. The immunogenic composition is formulated with excipients and adjuvants, including alum and monophosphoryl lipid A (MPL), and supports sterile injectable solution and lyophilized formulation modes.
Cell-free synthesized P. gingivalis Mfa1/HA1/HA2 elicits antigen-specific IgG responses, including ELISA-based measurements and EC50. The vaccine is also described as protecting against P. gingivalis-induced oral bone loss, including outcomes associated with the cementum-enamel junction (CEJ) and alveolar bone crest (ABC), with protection reported across adjuvants and comparable to heat-killed whole-organism delivery.
Claims Coverage
The independent claims cover two recombinant polypeptides forming an immunogenic composition, with each antigen sequence defined by at least 80% sequence homology to specified SEQ ID NOs. Dependent claims add excipient-containing vaccine formulations and methods of immunization and periodontitis-related outcome reduction, including Porphyromonas-associated disease and non-human mammal subjects.
Homologous recombinant Mfa1 plus HA1/HA2 immunogenic composition
An immunogenic composition comprising a first recombinant polypeptide with an Mfa1 antigen sequence having at least 80% sequence homology to SEQ ID NO: 4, and a second recombinant polypeptide comprising an HA1 antigen sequence having at least 80% sequence homology to SEQ ID NO: 5 and an HA2 antigen sequence having at least 80% sequence homology to SEQ ID NO: 6.
Homologous recombinant Mfa1 plus HA1/HA2 immunogenic composition defined by alternate SEQ ID NOs
An immunogenic composition comprising a first recombinant polypeptide with an Mfa1 antigen sequence having at least 80% sequence homology to SEQ ID NO: 1, and a second recombinant polypeptide comprising an HA1 antigen sequence having at least 80% sequence homology to SEQ ID NO: 2 and an HA2 antigen sequence having at least 80% sequence homology to SEQ ID NO: 3.
Excipient-containing vaccine formulation
A vaccine formulation comprising the immunogenic composition of the respective independent claim together with at least one excipient.
Immunization against periodontal disease by administering an immunologically effective amount
A method of immunizing a subject against periodontal disease by administering an immunologically effective amount of the vaccine formulation including the immunogenic composition of the relevant claim.
Periodontal disease associated with a Porphyromonas bacterium selected from specified species
The method in which periodontal disease is associated with a Porphyromonas bacterium selected from the specified group of species, including Porphyromonas gingivalis and Porphyromonas gulae and other listed Porphyromonas species.
Non-human mammal subject immunization
The immunization method carried out with the subject being a non-human mammal.
Reducing risk of developing periodontitis
A method of reducing the risk of developing periodontitis in a subject by administering an immunologically effective amount of the immunogenic composition.
Reducing bone loss or inflammation from periodontal disease
A method of reducing bone loss or inflammation from periodontal disease by administering an immunologically effective amount of the immunogenic composition to a subject needing treatment.
Overall, the claims cover an immunogenic composition of homologous recombinant Porphyromonas-associated Mfa1 and RgpA-derived HA1/HA2 antigens defined by at least 80% sequence homology to specified SEQ ID NOs. The dependent claims extend coverage to excipient-containing vaccine formulations and administration-based methods for immunization and for reducing periodontitis-related risk, including reduced bone loss and reduced inflammation, with further narrowing to Porphyromonas-associated periodontal disease and non-human mammal subjects.
Stated Advantages
Elicits antigen-specific IgG responses (ELISA/EC50 measurements).
Protects against P. gingivalis-induced oral bone loss.
Provides protection across adjuvants.
Protection is comparable to heat-killed whole-organism protection.
Reduces risk of periodontitis.
Reduces periodontal disease inflammation.
Documented Applications
Immunization against periodontal disease/periodontitis by administering the vaccine formulation including the immunogenic polypeptides.
Treating periodontal disease by reducing bone loss and/or inflammation associated with periodontal disease.
Prophylaxis/reducing risk of periodontitis by administering the immunogenic composition.
Use in an immunization context involving a non-human mammal subject.
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