Immunogenic composition

• US 9,789,179 B2
• Filed: 06/23/2006
• Issued: 10/17/2017
• Est. Priority Date: 06/27/2005
• Status: Active Grant

• Current Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Original Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Inventors: Biemans, Ralph Leon, Boutriau, Dominique, Capiau, Carine, Denoel, Philippe, Duvivier, Pierre, Poolman, Jan
• Primary Examiner(s): Navarro, Albert
• Assistant Examiner(s): Ford, Vanessa L
• Application Number:
  US11/917,610
• Publication Number:
  US 20090041802A1
• Time in Patent Office: 4,134 Days
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/62 characterised by the link between antigen and carrier
• CPC Class Codes: A61K 2039/627 characterised by the linker
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/0017 Combination vaccines based on whole cell diphtheria-tetanus-pertussis
• CPC Class Codes: A61K 39/0018 Combination vaccines based on acellular diphtheria-tetanus-pertussis
• CPC Class Codes: A61K 39/05 Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium Mycobacterium A61K39/04
• CPC Class Codes: A61K 39/08 Clostridium, e.g. Clostridium tetani
• CPC Class Codes: A61K 39/092 Streptococcus
• CPC Class Codes: A61K 39/095 Neisseria
• CPC Class Codes: A61K 39/099 Bordetella
• CPC Class Codes: A61K 39/102 Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
• CPC Class Codes: A61K 39/116 Polyvalent bacterial antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/385 Haptens or antigens, bound to carriers
• CPC Class Codes: A61P 11/04 : for throat disorders
• CPC Class Codes: A61P 11/14 : Antitussive agents
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 3/00 : Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms preparation by hydrolysis of di-or polysaccharides C13; separation or purification of sucrose, glucose, fructose, lactose or maltose C13
• CPC Class Codes: C12N 2730/10134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16234 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16271 : Demonstrated in vivo effect
• CPC Class Codes: C12N 2770/32634 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present application discloses an immunogenic composition comprising N. meningitidis capsular polysaccharides from at least one of serogroups A, C, W135 and Y conjugated to a carrier protein to produce a N. meningitidis capsular polysaccharide conjugate, wherein the average size of each N. meningitidis polysaccharide is above 50 kDa.

Claims

1. An immunogenic composition comprising Neisseria meningitidis (N. meningitidis) capsular polysaccharides from at least two of serogroups A, C, W135 and Y comprising N. meningitidis serogroup C capsular polysaccharide having an average size of above 75 kDa, conjugated to a carrier protein to produce a N. meningitidis capsular polysaccharide conjugate, and microfluidised N. meningitidis serogroup Y (MenY) capsular polysaccharide having an average size of above 120 kDa, conjugated to a carrier protein to produce a N. meningitidis capsular polysaccharide conjugate, wherein the average size of each N. meningitidis polysaccharide is above 50 kDa.

2. The immunogenic composition of claim 1 comprising N. meningitidis capsular polysaccharides from at least one of serogroups A, C, W135 and Y conjugated to a carrier protein to form N. meningitidis conjugates, wherein each N. meningitidis polysaccharide is either a native polysaccharide that has not been reduced in size or is a polysaccharide that has been reduced in size no more than 10-fold relative to the weight average molecular weight of the native polysaccharide.

3. The immunogenic composition of claim 1 wherein at least one N. meningitidis capsular polysaccharide other than MenY is sized by microfluidization.

4. The immunogenic composition of claim 1 wherein each N. meningitidis capsular polysaccharide is sized by a factor of no more than ×

10 relative to the weight average molecular weight of the native polysaccharide.

5. The immunogenic composition of claim 1 wherein the N. meningitidis conjugates are made from a mixture of native polysaccharides and polysaccharides that are sized by a factor of no more than ×

10 relative to the weight average molecular weight of the native polysaccharide.

6. The immunogenic composition of claim 5 wherein capsular polysaccharides from serogroup Y are sized by a factor of no more than ×

10 relative to the weight average molecular weight of the native polysaccharide.

7. The immunogenic composition of claim 5 wherein capsular polysaccharides from serogroups A and C are native and polysaccharides from serogroups W135 and Y are sized by a factor of no more than ×

10 relative to the weight average molecular weight of the native polysaccharide.

8. The immunogenic composition of claim 1 comprising a N. meningitidis serogroup A (MenA) capsular polysaccharide having an average size of above 50 kDa, 75 kDa, 100 kDa or an average size of between 50-100 kDa or 55-90 KDa or 60-80 kDa.

9. The immunogenic composition of claim 1 comprising a N. meningitidis serogroup C (MenC) capsular polysaccharide having an average size of above 100 kDa or between 100-200 kDa, 100-150 kDa, 80-120 kDa, 90-110 kDa, 150-200 kDa, 120-240 kDa, 140-220 kDa, 160-200 kDa or 190-200 kDa.

10. The immunogenic composition claim 1 wherein each N. meningitidis capsular polysaccharide is conjugated to a carrier protein independently selected from the group consisting of tetanus toxoid (TT), diphtheria toxoid (DT), cross-reacting material 197 (CRM197), fragment C of tetanus toxoid (TT) and protein D.

11. The immunogenic composition of claim 1 wherein each N. meningitidis capsular polysaccharide is conjugated to the same carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.

12. The immunogenic composition of claim 1 further comprising a Haemophilus influenzae b (H. influenzae b) capsular saccharide conjugated to a carrier protein.

13. The immunogenic composition of claim 12 wherein the H. influenzae b capsular saccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.

14. The immunogenic composition of claim 12 wherein the same carrier protein is used in the Hib conjugate and two or more of the at least two further bacterial saccharide conjugates.

15. The immunogenic composition of claim 1 comprising a N. meningitidis serogroup B outer membrane vesicle preparation or capsular saccharide.

16. A vaccine comprising the immunogenic composition of claim 1 and a pharmaceutically acceptable carrier.

17. A vaccine kit for concomitant or sequential administration comprising two multi-valent immunogenic compositions for conferring protection in a host against disease caused by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, Haemophilus influenzae and Neisseria meningitidis, said kit comprising a first container comprising:

tetanus toxoid (TT),

diphtheria toxoid (DT), and

whole cell or acellular pertussis components

and a second container comprising;

the immunogenic composition of claim 1.

18. A process for making the vaccine of claim 16 comprising the step of mixing the immunogenic composition of claim 1 with a pharmaceutically acceptable carrier.

19. A method of immunising a human host against disease caused by Neisseria meningitidis infection comprising administering to the host an immunoprotective dose of the immunogenic composition or vaccine of claim 1 or 17.

20. The method of treating or preventing a disease caused by Neisseria meningitidis comprising administering an immunogenic composition of claim 1.

21. The immunogenic composition of claim 1 further comprising a N. meningitidis serogroup W135 capsular polysaccharide having an average size ranging from 60-190 kDa.

22. An immunogenic composition, comprising Neisseria meningitidis (N meningitidis) capsular polysaccharides conjugated to a carrier protein or carrier proteins, wherein the N. meningitidis capsular polysaccharides of the capsular polysaccharide conjugates are from serogroups C (MenC) and Y (MenY), the MenC capsular polysaccharide of the capsular polysaccharide conjugates having an average size of above 75 kDa and the MenY capsular polysaccharide of the capsular polysaccharide conjugates having an average size ranging from 120 kDa to 140 kDa as measured by microfluidisation.

23. The immunogenic composition of claim 22, further comprising N. meningitidis capsular polysaccharide conjugates from at least one of serogroups A (MenA) and W135 (MenW135) conjugated to a carrier protein or carrier proteins to form a N. meningitidis capsular polysaccharide conjugate(s), wherein each N. meningitidis polysaccharide is either a native polysaccharide that has not been subjected to a process to reduce the size of the polysaccharide, or is a polysaccharide that has been reduced in size no more than 10-fold relative to the weight average molecular weight of the native polysaccharide, wherein the average size of each N. meningitidis polysaccharide is above 50 kDa.

24. The immunogenic composition of claim 23, wherein the size of at least one N. meningitidis capsular polysaccharide other than MenY is measured by microfluidisation.

25. The immunogenic composition of claim 23, wherein each N. meningitidis capsular polysaccharide is reduced in size no more than 10-fold relative to the weight average molecular weight of the native polysaccharide.

26. The immunogenic composition of claim 23, wherein the N. meningitidis conjugates comprise a mixture of native polysaccharide and capsular polysaccharide that is reduced in size no more than 10-fold relative to the weight average molecular weight of the native polysaccharide.

27. The immunogenic composition of claim 26, wherein N. meningitidis capsular polysaccharide from serogroup Y is reduced in size no more than 10-fold relative to the weight average molecular weight of the native polysaccharide.

28. The immunogenic composition of claim 26, further comprising N. meningitidis capsular polysaccharide from both serogroup W135 and from serogroup A, wherein capsular polysaccharides from serogroups A and C are native polysaccharides and polysaccharides from serogroups W135 and Y are reduced in size no more than 10-fold relative to the weight average molecular weight of the native polysaccharide.

29. The immunogenic composition of claim 22, further comprising a N. meningitidis serogroup A (MenA) capsular polysaccharide having an average size ranging from 60-80 kDa.

30. The immunogenic composition of claim 22, further comprising a N. meningitidis serogroup W135 capsular polysaccharide having an average size ranging from 60-190 kDa.

31. The immunogenic composition of claim 22, comprising a N. meningitidis serogroup C (MenC) capsular polysaccharide having an average size ranging from 100-200 kDa.

32. The immunogenic composition claim 22, wherein each N. meningitidis capsular polysaccharide is conjugated to a carrier protein independently selected from the group consisting of tetanus toxoid (TT), diphtheria toxoid (DT), cross-reacting material 197 (CRM197), fragment C of tetanus toxoid (TT) and protein D.

33. The immunogenic composition of claim 22, wherein each N. meningitidis capsular polysaccharide is conjugated to the same carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.

34. The immunogenic composition of claim 22, further comprising a Haemophilus influenzae b (Hib) capsular polysaccharide conjugated to a carrier protein.

35. The immunogenic composition of claim 34, wherein the Hib capsular polysaccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT and protein D.

36. The immunogenic composition of claim 34, wherein the same carrier protein is used in the Hib capsular saccharide conjugate and the at least two further bacterial capsular polysaccharide conjugates.

37. The immunogenic composition of claim 22, further comprising a N. meningitidis serogroup B outer membrane vesicle preparation.

38. A vaccine comprising the immunogenic composition of claim 22 and a pharmaceutically acceptable carrier.

39. A vaccine kit for concomitant or sequential administration comprising two multi-valent immunogenic compositions for conferring protection in a host against disease caused by Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, Haemophilia influenzae and Neisseria meningitidis, said kit comprising a first container comprising:

tetanus toxoid (TT),

diphtheria toxoid (DT), and

whole cell or acellular pertussis components;

and a second container comprising;

the immunogenic composition of claim 33.