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KR-20260068095-A - Immunogenic composition containing an ajuvant added to a conjugated pneumococcus capsular saccharide antigen and its use

KR20260068095AKR 20260068095 AKR20260068095 AKR 20260068095AKR-20260068095-A

Abstract

The present invention relates to a novel immunogenic composition containing an adjuvant, comprising a conjugated pneumococcal capsular saccharide antigen (sugar conjugate) and a saponin-containing liposomal adjuvant. The immunogenic composition of the present invention will typically comprise a sugar conjugate, wherein the saccharide is derived from a serotype of Streptococcus pneumoniae. The present invention also relates to the vaccination of human subjects, particularly infants and the elderly, against pneumococcal infection using the novel immunogenic composition.

Inventors

  • 카네브스키, 이시스
  • 수렌드란, 나빈

Assignees

  • 화이자 인코포레이티드

Dates

Publication Date
20260513
Application Date
20240911
Priority Date
20230914

Claims (20)

  1. An immunogenic composition comprising a glycoconjugate from a different serotype of S. pneumoniae, a monophosphoryl lipid A (MPLA)-containing liposomal composition, and a saponin-containing liposomal ajuvant comprising at least one saponin, wherein the liposomal composition comprises i) a lipid bilayer comprising phospholipids and ii) cholesterol.
  2. In claim 1, an immunogenic composition in which the saponin is QS-21.
  3. An immunogenic composition according to claim 1 or 2, wherein the phospholipids are DMPC and DMPG.
  4. An immunogenic composition according to claim 1, wherein the saponin-containing liposomal ajuvant comprises monophosphoryl lipid A (MPLA), QS-21, DMPC, DMPG, and cholesterol in a phosphate buffer.
  5. An immunogenic composition according to any one of claims 1 to 4, wherein MPLA is monophosphoryl 3-deacyl lipid A.
  6. An immunogenic composition comprising about 0.1 to about 1.0 mg/mL or more of MPLA according to any one of claims 1 to 5.
  7. An immunogenic composition comprising about 0.05 to about 1.0 mg/mL or more of QS-21 according to any one of claims 1 to 6.
  8. An immunogenic composition comprising about 0.5 to about 20 mg/mL or more of cholesterol according to any one of claims 1 to 7.
  9. An immunogenic composition comprising about 0.5 to about 20 mg/mL or more of DMPC according to any one of claims 1 to 8.
  10. An immunogenic composition comprising about 0.5 to about 3.0 mg/mL or more of DMPG according to any one of claims 1 to 9.
  11. An immunogenic composition according to claim 1, wherein the saponin-containing liposomal ajuvant comprises about 0.4 mg/mL of monophosphoryl 3-deacyl lipid A, about 0.2 mg/mL of QS-21, about 14 mg/mL of DMPC, about 1.6 mg/mL of DMPG, and about 11 mg/mL of cholesterol.
  12. An immunogenic composition according to claim 1, wherein the saponin-containing liposomal ajuvant comprises about 0.8 mg/mL of monophosphoryl 3-deacyl lipid A, about 0.4 mg/mL of QS-21, about 28 mg/mL of DMPC, about 3.2 mg/mL of DMPG, and about 22 mg/mL of cholesterol.
  13. An immunogenic composition according to claim 1, wherein the saponin-containing liposomal ajuvant comprises about 0.2 mg/mL of monophosphoryl 3-deacyl lipid A, about 0.1 mg/mL of QS-21, about 7 mg/mL of DMPC, about 0.8 mg/mL of DMPG, and about 5.5 mg/mL of cholesterol.
  14. An immunogenic composition according to any one of claims 1 to 13, wherein the saponin-containing liposomal ajuvant is homogeneous.
  15. An immunogenic composition according to any one of claims 1 to 13, wherein the saponin-containing liposomal ajuvant is heterogeneous.
  16. An immunogenic composition comprising at least 20 sugar conjugates from different serotypes of S. pneumoniae, in any one of claims 1 to 15.
  17. An immunogenic composition according to any one of claims 1 to 16, comprising a glycoconjugate from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F in S. pneumonia.
  18. An immunogenic composition according to any one of claims 1 to 16, comprising a glycoconjugate from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15A, 15B, 18C, 19A, 19F, 22F, 23A, 23B, 23F, 24F, 33F, and 35B in S. pneumonia.
  19. In any one of claims 1 to 18, S. pneumonia comprises a glycoconjugate from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15A, 15B, 18C, 19A, 19F, 22F, 23A, 23B, 23F, 24F, 33F, and 35B, and S. An immunogenic composition comprising at least 10 glycoconjugates from serotypes 2, 6C, 7C, 7F, 9N, 10B, 15C, 16F, 17F, 20A, 20B, 21, 22A, 24B, 27, 29, 31, 33B, 34, 35F, 38, 72, and 73 additionally to pneumonia.
  20. In claim 19, 35-a is an immunogenic composition which is a pneumococcal conjugate composition.

Description

Immunogenic composition containing an ajuvant added to a conjugated pneumococcus capsular saccharide antigen and its use The present invention relates to a novel immunogenic composition containing an adjuvant, comprising a conjugated pneumococcal capsular saccharide antigen (sugar conjugate) and a saponin-containing liposomal adjuvant. The immunogenic composition of the present invention will typically comprise a sugar conjugate, wherein the saccharide is derived from a serotype of Streptococcus pneumoniae. The present invention also relates to the vaccination of human subjects, particularly infants and the elderly, against pneumococcal infection using the novel immunogenic composition. Infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality worldwide. Pneumonia, febrile bacteremia, and meningitis are the most common manifestations of invasive pneumococcal disease, whereas bacterial spread within the respiratory tract can lead to middle ear infections, sinusitis, or recurrent bronchitis. Compared to invasive disease, non-invasive manifestations are typically less severe but significantly more common. In Europe and the United States, pneumococcal pneumonia is the most common community-acquired bacterial pneumonia, estimated to affect approximately 100 out of every 100,000 adults annually. Corresponding figures for febrile bacteremia and meningitis are 15–19 per 100,000 and 1–2 per 100,000, respectively. The risk for one or more of these conditions is significantly higher in infants and the elderly, as well as in immunocompromised individuals of any age. Even in economically advanced regions, invasive pneumococcal disease carries a high mortality rate; for adults with pneumococcal pneumonia, the mortality rate averages 10–20% and can exceed 50% in high-risk groups. Pneumonia is the most common cause of pneumococcal death worldwide. Streptococcus pneumoniae (pneumococcus), the causative agent of pneumococcal disease, is a Gram-positive, encapsulated coccus surrounded by a polysaccharide capsule. Differences in the composition of these capsules allow for serological distinction between approximately 91 capsule types, some of which are frequently associated with pneumococcal disease, while others are rarely associated. Invasive pneumococcal infections include pneumonia, meningitis, and febrile bacteremia; among common non-invasive signs are otitis media, sinusitis, and bronchitis. The pneumococcal conjugate vaccine (PCV) is a pneumococcal vaccine used to protect against disease caused by S. pneumoniae (Pneumococcus). Currently, there are five types of PCV vaccines available on the global market: Prevnar® (called Prevenar in some countries) (7-valent vaccine), Synflorix® (10-valent vaccine), Prevnar 13® (13-valent vaccine), Vaxneuvance™ (15-valent vaccine), and Prevnar 20™ (20-valent vaccine). The recent emergence of widespread microbial resistance to essential antibiotics and the increasing number of immunocompromised people highlight the need for pneumococcal vaccines with much broader protection. In particular, there is a need to address remaining unmet medical needs regarding the coverage of pneumococcal disease due to serotypes not found in Prevenar 13® and the potential for serotype replacement over time. Specific disease-causing serotypes beyond the 13 types of Prevenar 13® vary by region and population, and this may change over time due to the acquisition of antibiotic resistance, the introduction of pneumococcal vaccines, and secular trends of unknown origin. There is a need for immunogenic compositions that can be used to induce an immune response against additional Streptococcus pneumoniae serotypes in humans, particularly in children under 2 years of age. The purpose of the novel immunogenic composition of the present invention is to provide adequate protection against additional S. pneumonia serotypes not found in Prevenar 20™. In one aspect, the purpose of the immunogenic composition of the present invention is to maintain the immune response against the serotypes currently covered by said vaccine while providing adequate protection against additional S. pneumonia serotypes not found in Vaxneuvance™ and/or Prevenar 20™. Fig. 1. Effect of QS-21-containing liposomal ajuvant on PCV20 OPA titers at 1/4 dose. ST3-specific opsonization titers measured from serum collected at 4 weeks after the first administration from juvenile rhesus macaques. Each dot represents an individual animal, and data are expressed as geometric mean titers for OPA with a 95% confidence interval. LLOQ - Lower limit of quantification. QS-21 adj - QS-21-containing liposomal ajuvant. Fig. 2. Effect of QS-21-containing liposomal ajuvant on PCV20 IgG titers at 1/4 dose. ST3-specific IgG titers measured from serum collected at 4 weeks after the first administration from juvenile rhesus macaques. Each dot represents an individual animal, and data are expressed as μg/ml for IgG with a 95% confidence in