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KR-20260068102-A - Product and method for inducing an immune response against bacteria

KR20260068102AKR 20260068102 AKR20260068102 AKR 20260068102AKR-20260068102-A

Abstract

The present invention relates to peptides, fusion proteins, and compositions suitable for inducing an immune response against bacteria. The present invention also relates to the treatment or prevention of infections caused by sepsis-causing bacteria, and the treatment and prevention of pathologies caused by such bacteria. Such pathologies include sepsis, pneumonia, meningitis, endocarditis, enteritis, urinary tract infections, soft tissue infections, gastrointestinal infections, bloodstream infections, encephalitis, premature birth, and stillbirth.

Inventors

  • 마두레이라 페드로 조르그 폰세카
  • 비에이라 마르타 비르기니아 모타
  • 쿠라도 릴리아나 알메이다
  • 테익세이라 카를라 안드레이아 피달고
  • 피달고 아나 파트리시아 피구에이레도
  • 레모스 필리파 글라우시아 로드리게스
  • 노구에이라 크리스티아나 안드레이아 페레이라
  • 카스탄헤이라 페드로 미구엘 디아스

Assignees

  • 임뮨테프, 에스에이

Dates

Publication Date
20260513
Application Date
20240905
Priority Date
20230906

Claims (20)

  1. A peptide comprising the amino acid sequence according to SEQ ID NO. 3 (TQTTEITAVGDQLVKTVA).
  2. The peptide of claim 1, wherein the peptide has a length of 150 residues, 100 residues, 50 residues; or 30 residues or less.
  3. A peptide according to claim 1 or 2, wherein the flanking sequence of SEQ ID NO. 3 is derived from SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, or SEQ ID NO. 8.
  4. A peptide according to any one of paragraphs 1 to 3, wherein the flanking sequence of SEQ ID NO. 3 is derived from SEQ ID NO. 5.
  5. A peptide according to any one of claims 1 to 4, wherein the peptide comprises 8, 7, 6, 5, 4, or fewer than 3 consecutive residues from the sequence in SEQ ID NO. 9.
  6. A peptide according to any one of claims 1 to 5, wherein the peptide comprises an N-terminal or C-terminal cysteine.
  7. A peptide according to any one of claims 1 to 6, wherein the peptide comprises beta-alanine.
  8. A peptide according to any one of claims 1 to 7, wherein the peptide comprises SEQ ID NO. 12 (TQTTEITAVGDQLVKTVA(bALA)C).
  9. A peptide according to any one of claims 1 to 8, wherein the peptide has 0 to 12 additional amino acids on the N-terminal and/or C-terminal side of SEQ ID NO. 3 or SEQ ID NO. 12.
  10. A peptide according to any one of claims 1 to 9, wherein the peptide is a peptide according to SEQ ID NO. 12.
  11. A peptide according to any one of claims 1 to 10, wherein the peptide is connected to a carrier protein.
  12. A peptide according to any one of claims 1 to 11, wherein the peptide comprises a cysteine residue and the carrier protein is connected to the peptide through the cysteine residue.
  13. A fusion protein comprising a peptide according to any one of claims 1 to 12.
  14. A fusion protein according to claim 13, wherein the fusion protein comprises one or more peptides according to any one of claims 1 to 12.
  15. A fusion protein according to claim 13 or 14, wherein the fusion protein comprises the amino acid sequence according to SEQ ID NO. 13 (EVKEGGFEVNGKFIKVSA) and/or the amino acid sequence according to SEQ ID NO. 14 (DVTVEQVNEAMKNASNESF).
  16. As a composition or kit, A peptide according to any one of claims 1 to 12 or a fusion protein according to any one of claims 13 to 15, and A composition or kit comprising: a peptide comprising an amino acid sequence according to SEQ ID NO. 13 or a sequence according to SEQ ID NO. 13 having one or more additions, substitutions, or deletions; and/or a peptide comprising an amino acid sequence according to SEQ ID NO. 14 or a sequence according to SEQ ID NO. 14 having one or more additions, substitutions, or deletions.
  17. A composition or kit comprising a first peptide according to any one of claims 1 to 12, a second peptide comprising an amino acid sequence according to SEQ ID NO. 13, and a third peptide comprising an amino acid sequence according to SEQ ID NO. 14.
  18. In paragraph 16 or 17, A peptide containing SEQ ID NO. 13 contains SEQ ID NO. 15 (EVKEGGFEVNGKFIKVSA(bALA)C) and/or; A composition or kit comprising a peptide containing SEQ NO. 14 and SEQ NO. 16 (DVTVEQVNEAMKNASNESF(bALA)C).
  19. In any one of claims 16 to 18, the peptide comprising SEQ ID NO. 13 (i) length of 150 residues, 100 residues, 50 residues, or 30 residues or less; (ii) comprising a flanking sequence of SEQ ID NO 13 derived from SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, or SEQ ID NO 8, and/or; (iii) comprising the flanking sequence of SEQ ID NO. 13 derived from SEQ ID NO. 7 and/or; (iv) comprising 8, 7, 6, 5, 4, or fewer than 3 consecutive residues from the sequence in SEQ ID NO. 9; and/or; (v) A composition or kit having 0 to 12 additional amino acids on the N-terminal and/or C-terminal side of SEQ ID NO. 13 or SEQ ID NO. 15.
  20. In any one of claims 16 to 19, the peptide comprising SEQ ID NO. 14 (i) length of 150 residues, 100 residues, 50 residues, or 30 residues or less; (ii) comprising a flanking sequence of SEQ ID NO 14 derived from SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, or SEQ ID NO 8, and/or; (iii) comprising the flanking sequence of SEQ ID NO. 14 derived from SEQ ID NO. 6 and/or; (iv) comprising 8, 7, 6, 5, 4, or fewer than 3 consecutive residues from the sequence in SEQ ID NO. 9; and/or; (v) A composition or kit having 0 to 12 additional amino acids on the N-terminal and/or C-terminal side of SEQ ID NO. 14 or SEQ ID NO. 16.

Description

Product and method for inducing an immune response against bacteria The present invention relates to peptides, fusion proteins, and compositions suitable for inducing an immune response against bacteria. The present invention also relates to the treatment or prevention of infections caused by sepsis-inducing bacteria, and the treatment and prevention of pathologies caused by such bacteria. Such pathologies include sepsis, pneumonia, meningitis, endocarditis, enteritis, urinary tract infections, soft tissue infections, gastrointestinal infections, bloodstream infections, encephalitis, premature birth, and stillbirth. Bacterial infections are a leading cause of death worldwide. Recent studies estimated that 7.7 million people died in 2019 from complications associated with bacterial infections. Among these, Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae , Streptococcus pneumoniae , and Streptococcus agalactiae (commonly referred to as Streptococcus of Group B, GBS) are responsible for 53.6% of these deaths. The inventors previously described that the neutralization of extracellular bacterial glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a good strategy for preventing or treating infections caused by the aforementioned bacteria (see reference: e.g., WO2015/189422 A1). Extracellular bacterial GAPDH is an IL-10-inducing protein that induces systemic immunosuppression in the host very early after infection (Reference: Madureira, P., et al, PLoS Pathog, 2011. 7(11): p. e1002363). Extracellular bacterial GAPDH exhibits a high degree of sequence identity among the aforementioned bacterial species. Nevertheless, humans also possess GAPDH. Bacterial and human GAPDH may share 20-40% identity. Therefore, the inventors have described a list of peptides that can be used as targets for immunotherapies aimed at neutralizing bacterial GAPDH without any cross-reactivity to human homologues (Reference: WO2015/189422 A1). These peptides are exposed to bacterial GAPDH but are completely absent from human GAPDH. From each bacterial GAPDH, the inventors selected a list of 7 to 12 peptides in the range of 9 to 22 amino acids in length that could meet these criteria. The inventors also previously demonstrated that IgG-dependent antibody neutralization of bacterial GAPDH can provide protection against infection (see: Madureira, P., et al. , PLoS Pathog, 2011. 7(11): p. e1002363). There is still a need for vaccine compositions effective against a wide range of bacteria. Summary of the Invention In the first aspect, a peptide comprising the amino acid sequence according to SEQ ID NO. 3 (TQTTEITAVGDQLVKTVA) is provided. In a second aspect, a fusion protein comprising a peptide according to a first aspect is provided. In a third aspect, a composition or kit comprising a peptide of the first aspect or a fusion protein of the second aspect is provided. In one embodiment, the composition or kit comprises the peptide of the first aspect or the fusion protein of the second aspect, and a peptide comprising an amino acid sequence according to SEQ ID NO. 13 or a sequence according to SEQ ID NO. 13 having one or more additions, substitutions, or deletions; and/or a peptide comprising an amino acid sequence according to SEQ ID NO. 14 or a sequence according to SEQ ID NO. 14 having one or more additions, substitutions, or deletions. In one embodiment, a composition or kit is provided comprising a first peptide which is a peptide of the first aspect, a second peptide comprising an amino acid sequence according to SEQ ID NO. 13, and a third peptide comprising an amino acid sequence according to SEQ ID NO. 14. In a fourth aspect, a first peptide comprising a sequence according to SEQ ID NO. 3 or a sequence according to SEQ ID NO. 3 having one or more additions, substitutions, or deletions; a second peptide comprising a sequence according to SEQ ID NO. 13 or a sequence according to SEQ ID NO. 13 having one or more additions, substitutions, or deletions; and a third peptide comprising a sequence according to SEQ ID NO. 14 or a sequence according to SEQ ID NO. 14 having one or more additions, substitutions, or deletions are provided. In one embodiment, a peptide comprising SEQ ID NO. 3 follows SEQ ID NO. 12; a peptide comprising SEQ ID NO. 13 follows SEQ ID NO. 15; and a peptide comprising SEQ ID NO. 14 follows SEQ ID NO. 16. In the fifth aspect, one or more nucleic acids encoding a peptide according to the first aspect, a fusion protein according to the second aspect, or a peptide of a composition or kit according to the fourth or fifth aspect are provided. In the sixth aspect, one or more vectors comprising one or more nucleic acids of the fifth aspect are provided. In the seventh aspect, a cell comprising one or more nucleic acids of the fifth aspect or one or more vectors of the sixth aspect is provided. In the eighth aspect, one or more pharmaceutical compositions are provided, comprising a peptide according to the first aspe