NZ770014B2 - Streptococcus pneumoniae capsular polysaccharides and immunogenic conjugate thereof - Google Patents
Streptococcus pneumoniae capsular polysaccharides and immunogenic conjugate thereof Download PDFInfo
- Publication number
- NZ770014B2 NZ770014B2 NZ770014A NZ77001419A NZ770014B2 NZ 770014 B2 NZ770014 B2 NZ 770014B2 NZ 770014 A NZ770014 A NZ 770014A NZ 77001419 A NZ77001419 A NZ 77001419A NZ 770014 B2 NZ770014 B2 NZ 770014B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- capsular polysaccharide
- serotype
- capsular
- streptococcus pneumoniae
- molecular weight
- Prior art date
Links
- 150000004676 glycans Chemical class 0.000 title claims abstract 33
- 229920001282 polysaccharide Polymers 0.000 title claims abstract 33
- 239000005017 polysaccharide Substances 0.000 title claims abstract 33
- 241000193998 Streptococcus pneumoniae Species 0.000 title claims abstract 15
- 229940031000 streptococcus pneumoniae Drugs 0.000 title claims abstract 15
- 230000002163 immunogen Effects 0.000 title claims abstract 14
- 102000014914 Carrier Proteins Human genes 0.000 claims abstract 6
- 108010078791 Carrier Proteins Proteins 0.000 claims abstract 6
- 108010071134 CRM197 (non-toxic variant of diphtheria toxin) Proteins 0.000 claims abstract 3
- 229960000814 tetanus toxoid Drugs 0.000 claims abstract 3
- 230000003647 oxidation Effects 0.000 claims 8
- 238000007254 oxidation reaction Methods 0.000 claims 8
- 238000000034 method Methods 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 229960005486 vaccine Drugs 0.000 claims 3
- 206010053555 Arthritis bacterial Diseases 0.000 claims 2
- 208000004020 Brain Abscess Diseases 0.000 claims 2
- 206010007882 Cellulitis Diseases 0.000 claims 2
- 206010010741 Conjunctivitis Diseases 0.000 claims 2
- 208000004575 Infectious Arthritis Diseases 0.000 claims 2
- 206010071699 Infectious pleural effusion Diseases 0.000 claims 2
- 208000010315 Mastoiditis Diseases 0.000 claims 2
- 206010031252 Osteomyelitis Diseases 0.000 claims 2
- 206010033078 Otitis media Diseases 0.000 claims 2
- 206010035664 Pneumonia Diseases 0.000 claims 2
- 206010040047 Sepsis Diseases 0.000 claims 2
- 206010062255 Soft tissue infection Diseases 0.000 claims 2
- 230000003213 activating effect Effects 0.000 claims 2
- 230000001580 bacterial effect Effects 0.000 claims 2
- 206010014665 endocarditis Diseases 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 208000022760 infectious otitis media Diseases 0.000 claims 2
- 201000011475 meningoencephalitis Diseases 0.000 claims 2
- 208000008494 pericarditis Diseases 0.000 claims 2
- 206010034674 peritonitis Diseases 0.000 claims 2
- 201000001223 septic arthritis Diseases 0.000 claims 2
- 208000013223 septicemia Diseases 0.000 claims 2
- 201000009890 sinusitis Diseases 0.000 claims 2
- 229920000936 Agarose Polymers 0.000 claims 1
- 239000011324 bead Substances 0.000 claims 1
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- -1 cyanoborohydride Chemical compound 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000011347 resin Substances 0.000 claims 1
- 229920005989 resin Polymers 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 208000035109 Pneumococcal Infections Diseases 0.000 abstract 1
- 241000194017 Streptococcus Species 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
- A61K39/092—Streptococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/315—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/315—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
- C07K14/3156—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci from Streptococcus pneumoniae (Pneumococcus)
Abstract
The objective of the present invention is to provide: an immunogenic composition comprising a Streptococcus pneumoniae polysaccharides-proteins conjugate, which comprises any one or more capsular polysaccharides selected from the group consisting of serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F, which are derived from Streptococcus , and one or more carrier proteins conjugated to each of the capsular polysaccharides; and a preparation method therefor. According to one embodiment of the present invention, provided is an immunogenic composition for preventing or treating a pneumococcal infection. In particular, the invention provides an immunogenic composition comprising 24 different streptococcus pneumoniae capsular polysaccharide-protein conjugates where the capsular polysaccharides from serotypes 1 and 5 are conjugated to tetanus toxoid and the capsular polysaccharides from serotypes 2, 3, 4, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F are conjugated to CRM197.
Claims (16)
1. An immunogenic composition comprising 24 different Streptococcus pneumoniae capsular polysaccharide-protein conjugates, wherein each capsular polysaccharide-protein conjugate 5 comprises a carrier protein conjugated to a capsular polysaccharide derived from a different serotype of Streptococcus pneumoniae, wherein the Streptococcus pneumoniae serotypes are selected from serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F; and 10 wherein the capsular polysaccharides from serotypes 1 and 5 are conjugated to tetanus toxoid and the capsular polysaccharides from serotypes 2, 3, 4, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F are conjugated to CRM197, 15 wherein the capsular polysaccharide from serotype 2 has a molecular weight of 100 to 400 kDa and a degree of oxidation of 2 to 18, wherein the capsular polysaccharide from serotype 9N has a molecular weight of 200 to 700 kDa and a degree of oxidation of 2 20 to 19, wherein the capsular polysaccharide from serotype 17F has a molecular weight of 400 to 900 kDa and a degree of oxidation of 1 to 22, and wherein the capsular polysaccharide from serotype 20 has a 25 molecular weight of 400 to 800 kDa and a degree of oxidation of 4 to 16.
2. The immunogenic composition of claim 1, wherein: the capsular polysaccharide-protein conjugate comprising the 30 capsular polysaccharide from serotype 2 has a molecular weight of 1,000 to 16,000 kDa; or the capsular polysaccharide-protein conjugate comprising the capsular polysaccharide from serotype 20 has a molecular weight of 1,000 to 4,000 kDa.
3. The immunogenic composition of claim 1 or claim 2, wherein: the weight ratio of the capsular polysaccharide from serotype 2 to the carrier protein is 0.5 to 2.0; or the weight ratio of the capsular polysaccharide from serotype 5 17F to the carrier protein is 0.5 to 18; or the weight ratio of the capsular polysaccharide from serotype 20 to the carrier protein is 1 to 5.
4. The immunogenic composition of any one of claims 1 to 3, wherein: 10 20 to 60% of the total molecular weight of the capsular polysaccharide-protein conjugate comprising the capsular polysaccharide from serotype 2 is present within 0.3 Kd in a 4% Cross-linked Agarose beads (CL-4B) column; or 15 to 60% of the total molecular weight of the capsular 15 polysaccharide-protein conjugate comprising the capsular polysaccharide from serotype 17F is present within 0.3 Kd in a CL- 4B column; or 70 to 90% of the total molecular weight of the capsular polysaccharide-protein conjugate comprising the capsular 20 polysaccharide from serotype 20 is present within 0.3 Kd in a CL- 4B column.
5. The immunogenic composition of any one of claims 1 to 4, wherein the immunogenic composition comprises a physiologically acceptable 25 vehicle.
6. A vaccine comprising an immunogenic composition of any one of claims 1 to 5 and a pharmaceutically acceptable excipient, carrier or diluent.
7. A method of preparing the immunogenic composition of any one of claims 1 to 5, the method comprising: (a) fermenting and dissolving bacterial cells which produce capsular polysaccharides derived from Streptococcus pneumoniae 35 serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F; (b) purifying the capsular polysaccharides from the bacterial cells; (c) activating the capsular polysaccharides with an oxidizing agent; and 5 (d) combining each of the capsular polysaccharides with a carrier protein to form a Streptococcus pneumoniae capsular polysaccharide-protein conjugate, wherein the capsular polysaccharides from serotypes 1 and 5 are conjugated to tetanus toxoid and the capsular polysaccharides 10 from serotypes 2, 3, 4, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F are conjugated to CRM197, wherein the capsular polysaccharide from serotype 2 has a molecular weight of 100 to 400 kDa and a degree of oxidation of 2 15 to 18, wherein the capsular polysaccharide from serotype 9N has a molecular weight of 200 to 700 kDa and a degree of oxidation of 2 to 19, wherein the capsular polysaccharide from serotype 17F has a 20 molecular weight of 400 to 900 kDa and a degree of oxidation of 1 to 22, and wherein the capsular polysaccharide from serotype 20 has a molecular weight of 400 to 800 kDa and a degree of oxidation of 4 to 16.
8. The method of claim 7, wherein the method further comprises hydrolyzing the capsular polysaccharide to size it, before step (c), in case of the capsular polysaccharides derived from serotypes 2 and 17F.
9. The method of claim 7 or claim 8, wherein the Streptococcus pneumoniae capsular polysaccharide-protein conjugate is formed by reacting with one or more reducing agents selected from the group consisting of cyanoborohydride, borane-pyridine and borohydride 35 exchange resin.
10. The method of any one of claims 7 to 9, wherein the activating step (c) comprises reacting 0.01 - 0.22 µg of periodate per 1 µg capsular polysaccharide at a temperature of 20 to 25ºC for 15 to 20 hours.
11. Use of an immunogenic composition of any one of claims 1 to 5 in the manufacture of a medicament for preventing or treating a disease or condition caused by Streptococcus pneumoniae. 10 12. The use of claim 11, wherein the disease or condition caused by
12.Streptococcus pneumoniae is pneumonia, sinusitis, otitis media, acute otitis media, cerebromeningitis, bacteriemia, septicemia, pyothorax, conjunctivitis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, mastoiditis, cellulitis, 15 soft tissue infection, or brain abscess.
13. Use of an immunogenic composition of any one of claims 1 to 5 in the manufacture of a medicament for inducing an immune response against Streptococcus pneumoniae.
14. Use of a vaccine of claim 6 in the manufacture of a medicament for preventing or treating a disease or condition caused by Streptococcus pneumoniae. 25
15. The use of claim 14, wherein the disease or condition caused by Streptococcus pneumoniae is pneumonia, sinusitis, otitis media, acute otitis media, cerebromeningitis, bacteriemia, septicemia, pyothorax, conjunctivitis, osteomyelitis, septic arthritis, endocarditis, peritonitis, pericarditis, mastoiditis, cellulitis, 30 soft tissue infection, or brain abscess.
16. Use of a vaccine of claim 6 in the manufacture of a medicament for inducing an immune response against Streptococcus pneumoniae.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20180045246 | 2018-04-18 | ||
| KR20180045245 | 2018-04-18 | ||
| KR20180045247 | 2018-04-18 | ||
| KR20180045248 | 2018-04-18 | ||
| PCT/KR2019/004717 WO2019203599A1 (en) | 2018-04-18 | 2019-04-18 | Streptococcus pneumoniae capsular polysaccharides and immunogenic conjugate thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ770014A NZ770014A (en) | 2024-05-31 |
| NZ770014B2 true NZ770014B2 (en) | 2024-09-03 |
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