Immunogenic composition

• US 8,398,983 B2
• Filed: 06/23/2006
• Issued: 03/19/2013
• 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 MARK
• Application Number:
  US11/917,726
• Publication Number:
  US 20080193476A1
• Time in Patent Office: 2,461 Days
• Field of Search: None
• US Class Current: 424/184.1
• 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 a Hib saccharide conjugate, at least one additional bacterial, for example N. meningitidis, saccharide conjugate(s), and a further antigen selected from the group consisting of whole cell pertussis and hepatitis B surface antigen, wherein the saccharide dose of the Hib saccharide conjugate is less than 5 ug.

Claims

1. An immunogenic composition comprising:

(a) a Haemophilis influenza type b (Hib) saccharide conjugate,

(b) an N. meningitidis capsular saccharide conjugate derived from a strain selected from the group consisting of serogroups A, B, C, W135 and Y,

(c) whole cell pertussis, and

(d) hepatitis B surface antigen,

wherein the saccharide dose of the Hib saccharide conjugate is less than 5 μ

g and the saccharide dose of the N. meningitidis capsular saccharide conjugate is less than 5 μ

g, and wherein the Geometric Mean Concentration (GMC) for whole cell pertussis or hepatitis B achieved with said immunogenic composition is higher than the GMC achieved after immunisation with said immunogenic composition containing a 5 μ

g saccharide dose of Hib saccharide conjugate and a 5 μ

g dose of N. meningitidis capsular saccharide conjugate.

2. The immunogenic composition of claim 1 wherein the saccharide dose of the N. meningitidis capsular saccharide conjugate is 1-4 μ

g.

3. The immunogenic composition of claim 1 comprising N. meningitidis serogroup C capsular saccharide (MenC).

4. The immunogenic composition of claim 1 comprising N. meningitidis serogroup A capsular saccharide (MenA).

5. The immunogenic composition of claim 1 comprising N. meningitidis serogroup Y capsular saccharide (MenY).

6. The immunogenic composition of claim 1 comprising N. meningitidis serogroup W135 capsular saccharide (MenW).

7. The immunogenic composition of claim 1 comprising diphtheria toxoid (DT) and tetanus toxoid (TT).

8. The immunogenic composition of claim 1 comprising a N. meningitidis serogroup B outer membrane vesicle preparation.

9. The immunogenic composition of claim 1 comprising a S. pneumoniae capsular saccharide derived from a strain 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.

10. The immunogenic composition of claim 1 comprising a S. typhi Vi capsular polysaccharide.

11. The immunogenic composition of claim 1 wherein the N. meningitidis capsular saccharide is conjugated to the same carrier protein as used in the Hib conjugate.

12. The immunogenic composition of claim 1 wherein the Hib saccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT, protein D, meningococcal outer membrane protein (OMPC) and pneumolysin.

13. The immunogenic composition of claim 1 wherein said N. meningitidis capsular saccharide is conjugated to a carrier protein selected from the group consisting of TT, DT, CRM197, fragment C of TT, protein D, OMPC and pneumolysin.

14. The immunogenic composition of claim 1 wherein the ratio of Hib to carrier protein in the Hib saccharide conjugate is between 1:

5 and 5;

1 weight/weight (w/w).

15. The immunogenic composition of claim 4 wherein the MenA saccharide has a molecular weight of above 50 kDa as measured by MALLS.

16. The immunogenic composition of claim 3 wherein the MenC saccharide has a molecular weight of above 50 kDa as measured by MALLS.

17. The immunogenic composition of claim 3 wherein MenC is at least partially O-acetylated such that at least 30% of the repeat units are O-acetylated at least one position.

18. The immunogenic composition of claim 4 wherein MenA is at least partially O-acetylated such that at least 50% of the repeat units are O-acetylated at least one position.

19. The immunogenic composition of claim 1 wherein the Hib saccharide conjugate and N. meningitidis saccharide conjugate are not adsorbed onto aluminum salts.

20. The immunogenic composition of claim 1 which is unadjuvanted.

21. A vaccine comprising the immunogenic composition of claim 1 and a pharmaceutically acceptable excipient.

22. The immunogenic composition of claim 1 where said GMC is measured by enzyme linked immunosorbent assay (ELISA).

23. The immunogenic composition of claim 1 where the GMC achieved for whole cell pertussis and the GMC achieved for hepatitis B is higher than the GMC achieved after immunisation with said immunogenic composition containing a 5 μ

g saccharide dose of Hib saccharide conjugate and a 5 μ

g dose of N. meningitidis capsular saccharide conjugate.

24. The immunogenic composition of claim 1 wherein the ratio of Hib to carrier protein in the Hib saccharide conjugate is between 1:

1 and 1;

4 w/w.

25. The immunogenic composition of claim 1 wherein the ratio of Hib to carrier protein in the Hib saccharide conjugate is between 1:

2 and 1;

3.5 w/w.

26. The immunogenic composition of claim 1 wherein the ratio of Hib to carrier protein in the Hib saccharide conjugate is around 1:

3 w/w.

27. The immunogenic composition of claim 4 wherein the MenA capsular saccharide has a molecular weight above 75 kDa as measured by MALLS.

28. The immunogenic composition of claim 4 wherein the MenA capsular saccharide has a molecular weight above 100 kDa as measured by MALLS.

29. The immunogenic composition of claim 4 wherein the MenA capsular saccharide has a molecular weight between 100-200 kDa as measured by MALLS.

30. The immunogenic composition of claim 4 wherein the MenA capsular saccharide has a molecular weight between 100-150 kDa as measured by MALLS.

31. The immunogenic composition of claim 4 wherein the MenA capsular saccharide has a molecular weight between 150-200 kDa as measured by MALLS.