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KR-20260066054-A - RNA vaccines for use in animal health

KR20260066054AKR 20260066054 AKR20260066054 AKR 20260066054AKR-20260066054-A

Abstract

The present invention relates to an RNA-containing vaccine composition for inducing an immune response against Porphyromonas gulae in a subject and the use thereof.

Inventors

  • 스미스 크리스토퍼
  • 레이놀즈 에릭

Assignees

  • 카드무스 애니멀 헬스 리미티드

Dates

Publication Date
20260512
Application Date
20240726
Priority Date
20230726

Claims (20)

  1. As an RNA polynucleotide, - One or more amino acid sequences of the active site of an Arg- or Lys-gingipain homologue of P. gulae , or a sequence at least 80% identical thereto; and/or - Encoding a protein comprising or consisting of the amino acid sequence of one or more adhesive binding motifs (ABMs) of the adhesive domain found in the surface complex of Arg- and Lys-gingipain homologues of P. goulae, or a sequence that is at least 80% identical thereto, and RNA polynucleotide that can be translated in mammalian cells.
  2. In claim 1, the protein encoded by the RNA - One or more amino acid sequences of the active site of an Arg- or Lys-zingipa homologue of P. goulae, or a sequence at least 80% identical to this; and - The amino acid sequence of one or more adhesion binding motifs (ABMs) of the adhesion domain found in the surface complex of Arg- and Lys-gingipa homologues of P. goulae, or RNA comprising or consisting of a sequence that is at least 80% identical to this.
  3. In claim 1 or 2, the protein encoded by the RNA polynucleotide - The amino acid sequence of the DUF2436 domain of the Arg- and Lys-gingipain homologue surface complex of P. gullae, or RNA containing a sequence that is at least 80% identical to this.
  4. In any one of claims 1 to 3, the protein encoded by the RNA polynucleotide - One or more amino acid sequences of the active site of an Arg- or Lys-zingipa homologue of P. goulae, or a sequence at least 80% identical to this; and - The amino acid sequence of one or more adhesion binding motifs (ABMs) of the adhesion domain found in the surface complex of Arg- and Lys-gingipa homologues of P. goulae, or RNA that is a chimeric or fusion protein containing or consisting of a sequence that is at least 80% identical to this.
  5. In any one of claims 1 to 4, the RNA encodes an amino acid sequence of an Arg-gingipa homologue of P. goulae, wherein the amino acid sequence is the amino acid sequence of SEQ ID NO. 4 (e.g., encoded by the RNA sequence presented in SEQ ID NO. 69), or an RNA comprising a sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 98%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.
  6. In any one of claims 1 to 5, the RNA encodes the amino acid sequence of the active site of a Lys-gingipa homologue of P. gullae, wherein the amino acid sequence is the amino acid sequence of SEQ ID NO. 2 (e.g., encoded by the RNA sequence presented in SEQ ID NO. 59), or an RNA comprising a sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 98%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical thereto.
  7. In any one of claims 1 to 6, the RNA i) an amino acid sequence of the active site of an Arg-zingipain homologue of P. goulae, or an amino acid sequence comprising or consisting of a sequence that is at least 80% identical to this; and ii) RNA encoding a chimeric or fusion protein comprising an amino acid sequence of the active site of a Lys-gingipain homologue of P. gullae, or an amino acid sequence comprising a sequence that is at least 80% identical to or formed therefrom.
  8. In any one of claims 1 to 7, the RNA encoding a chimeric or fusion protein comprising an amino acid sequence of the active site of an Arg- or Lys-gingipa homologue of P. gullae, or at least two amino acid sequences consisting thereof, or a sequence that is at least 80% identical to the same.
  9. In claim 8, the RNA in which the at least two amino acid sequences are located consecutively within the chimera or fusion protein.
  10. In claim 8, an RNA in which one of the at least two amino acid sequences is located at the N-terminus of the chimera or fusion protein, and the second of the at least two amino acid sequences is located at the C-terminus of the chimera or fusion protein.
  11. In claim 8, one of the at least two amino acid sequences is located at the N or C terminal of the chimera or fusion protein, and the second of the at least two amino acid sequences is located inside the chimera or fusion protein.
  12. In claim 8, the RNA in which the at least two amino acid sequences are located at (both) the N-terminus of the chimera or fusion protein, or the at least two amino acid sequences are located at (both) the C-terminus of the chimera or fusion protein.
  13. In any one of paragraphs 4 to 12, the chimera or fusion protein encoded by the RNA polynucleotide - The amino acid sequence of the DUF2436 domain of the Arg- and Lys-gingipain surface complex of P. gullae, or RNA containing a sequence that is at least 80% identical to this.
  14. In Clause 13, the above RNA - One or more amino acid sequences of the active site of an Arg- or Lys-zingipa homologue of P. goulae, or a sequence at least 80% identical to this; and - The amino acid sequence of one or more adhesive binding motifs (ABMs) of the adhesive domain found in the surface complex of Arg- and Lys-gingipa homologues of P. goulae, or encoding a sequence that is at least 80% identical to this; The amino acid sequence of the DUF2436 domain is RNA located between the amino acid sequence of the active site of the zingipine of P. gullae and the amino acid sequence of one or more adhesion binding motifs (ABM).
  15. In either claim 13 or 14, said RNA encodes a chimeric or fusion protein comprising the amino acid sequence of the DUF2436 domain of the Arg and Lys gingipine surface complex of P. gullae, wherein said amino acid sequence comprises or consists of the amino acid sequence of SEQ ID NO. 22 encoded by the RNA sequence presented in SEQ ID NO. 70, or a sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 98%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the above.
  16. In either claim 13 or 14, the RNA encodes a chimeric or fusion protein comprising the amino acid sequence of the DUF2436 domain of the Arg and Lys gingipine surface complex of P. gullae, wherein the amino acid sequence comprises or consists of the amino acid sequence of SEQ ID NO. 19 encoded by the RNA sequence presented in SEQ ID NO. 71, or a sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 98%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the same.
  17. In claim 16, RNA in which one or more cysteine residues of the DUF2436 domain are substituted with serine or valine residues or alanine residues, preferably with serine residues (e.g., as shown in any of SEQ ID NOs 20 and 21).
  18. In claim 17, an RNA in which at least two cysteine residues of the DUF2436 domain are substituted, and optionally all of at least three or four cysteine residues among the cysteine residues are substituted.
  19. RNA encoding one or more adhesive bonding motifs (ABM) comprising or consisting of the amino acid sequences of ABM2 and ABM1 in any one of claims 1 to 18.
  20. In claim 19, an RNA encoding an amino acid sequence of a polypeptide comprising ABM2 and ABM1 as presented in SEQ ID NO. 6 and SEQ ID NO. 6, respectively, or comprising an amino acid sequence as presented in SEQ ID NO. 8 (ABM2+1), or comprising a sequence identical to the above by at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 98%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.

Description

RNA vaccines for use in animal health The present invention relates to an RNA-containing vaccine composition for inducing an immune response against Porphyromonas gulae in a subject and the use thereof. Related applications This application claims priority to Australian provisional application AU 2023902376, the entire contents of which are incorporated herein by reference. The accumulation of dental plaque at the gum line of the teeth causes inflammation of the gums (gingivitis). Chronic gingivitis involves the proliferation of periodontal pathogens, specifically Porphyromonas sp., at the base of the periodontal pocket, leading to a chronic infection that can develop into a serious disease. This severe form of periodontal disease is called periodontitis, and it can lead to tooth loss as the immune system attempts to eliminate the infection. Periodontitis is an inflammatory disease of the tooth-supporting tissues in both humans and pets, associated with dysbiotic subgingival plaque, which leads to the destruction of these tissues and loss of tooth attachment. By the age of three, more than 80% of dogs and more than 70% of cats show symptoms of periodontitis. Therefore, the disease burden caused by periodontitis in the pet population is significant. The most common periodontal pathogen in pets, especially dogs, is Porphyromonas gullae (P. gullae). Currently, there are no commercially approved treatments available to prevent or reduce the incidence and/or severity of P. gula infection in companion animals, or to treat P. gula infection and disease. Therefore, new or improved approaches are needed for the design and manufacture of agents for the treatment, prevention, or reduction of severity of P. gula infection. Any reference to any prior art in this specification does not constitute an acknowledgment or implied that such prior art forms part of general knowledge in any jurisdiction, nor does it imply that such prior art is reasonably understood by a person skilled in the art,/or is considered relevant, or can be combined with other prior art. Summary of the Invention The first aspect of the present invention is, - One or more amino acid sequences of the active site of an Arg- or Lys-gingipain homologue of P. goulae, or a sequence at least 80% identical thereto; and/or - As an RNA polynucleotide encoding a protein comprising or consisting of an amino acid sequence of one or more adhesive binding motifs (ABMs) of an adhesive domain found in the surface complex of Arg- and Lys-gingipain homologues of P. goulae, or a sequence that is at least 80% identical thereto, The above polynucleotide provides an RNA polynucleotide that can be translated in mammalian cells. In any embodiment, the protein encoded by the RNA polynucleotide is - Includes the amino acid sequence of the DUF2436 domain of the Arg- and Lys-zingipain homologue surface complex of P. goulae, or a sequence that is at least 80% identical to this. Optionally, the protein encoded by RNA may include the aforementioned domains in any order, for example, one or more amino acid sequences of the active site of an Arg- or Lys-gingipain homologue of P. goulae may be located at the N-terminus of the amino acid sequence of one or more adhesion binding motifs (ABM) and/or the amino acid sequence of the DUF2436 domain; or one or more amino acid sequences of the adhesion binding motifs (ABM) of the adhesion domain may be located at the N-terminus of the amino acid sequence of one or more amino acid sequences of the active site of an Arg- or Lys-gingipain homologue of P. goulae and/or the amino acid sequence of the DUF2436 domain. The domains may be directly bound in the context of a chimeric or fusion protein, or may be bound through a linker region of one or more amino acid residues as further defined herein. (i.e., the protein may comprise or be composed of the following from the N-terminus to the C-terminus: active site (K) - ABM(A); or active site (R) - ABM(A); or active site (K) - DUF 2436(D); or active site (R) - DUF2436(D); or AMB(A) - active site (K); or ABM(A) - active site (R); or DUF2436(D) - active site (K); or DUF2436(D) - active site (R); or active site (R) - ABM(A) - active site (K); or active site (R) - ABM(A) - active site (R); or active site (K) - ABM(A) - active site (R); or DUF2436(D) - ABM(A); or DUF2436(D) - ABM(A) - active site (R) or (K). In any embodiment of the present invention, the RNA polynucleotide is in the form of a messenger RNA (mRNA) molecule. However, it should be understood that the RNA polynucleotide may be any suitable form that is translated in mammalian cells to enable the synthesis of proteins encoded by RNA. In certain embodiments, the RNA polynucleotide may consist entirely of ribose-containing nucleotides, or alternatively may comprise a combination of ribose-containing nucleosides and 2'-deoxyribose-containing nucleotides. In any embodiment, the RNA polynucleotide may be a synthetic RNA molecule. In any embodiment, the