Vaccines comprising aluminium adjuvants and histidine

• US 20050158334A1
• Filed: 07/26/2002
• Published: 07/21/2005
• Est. Priority Date: 07/26/2001
• Status: Active Grant

• Current Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Original Assignee: Novartis Vaccines And Diagnostics Srl (Novartis Ag)
• Inventors: Maffei, Massimo, Contorni, Mario
• Granted Patent: US 7,348,006 B2
• Time in Patent Office: Days
• US Class Current: 424/190.100
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/095 Neisseria
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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

To improve the stability of vaccines comprising aluminum salt(s), the invention uses the amino acid histidine. This can improve pH stability and adjuvant adsorption and can be reduce antigen hydrolysis. Histidine is preferably presen during adsorption to the aluminium salt(s). The antigen in the vaccine may be a protein or a saccharide and is preferably from N. meningitidis.

Claims

1. A composition comprising an antigen, an aluminium salt and histidine.

2. The composition of claim 1, wherein the antigen is a protein antigen or a saccharide antigen.

3. The composition of claim 1 or claim 2, wherein the antigen is a bacterial antigen selected from the group consisting of:

a protein antigen from N. meningitidis;

an outer-membrane vesicle (OMV) preparation from N. meningitidis;

a saccharide antigen from N. meningitidis;

a saccharide antigen from Streptococcus pnemnoniae;

an antigen from Bordetella pertussis;

a diphtheria antigen;

a tetanus antigen;

a protein antigen from Helicobacter pylori;

a saccharide antigen from Haemophilus influenzae;

an antigen from N. gonorrhoeae;

an antigen from Chlamydia pneumoniae;

an antigen from Chlamydia trachomatis;

an antigen from Porphyromonas gingivalis;

an antigen from Moraxella catarrhalis;

an antigen from Streptococcus agalactiae;

an antigen from Streptococcus pyogenes; and

an antigen from Staphylococcus aureus.

4. The composition of claim 3, wherein the antigen is from Neisseria menningitidis serogroup B.

5. The composition of claim 2, wherein the saccharide antigen is a conjugated oligosaccharide antigen.

6. The composition of claim 2, wherein a protein antigen is replaced by nucleic acid encoding the protein.

7. The composition of claim 1, wherein the antigen is adsorbed to the aluminium salt.

8. The composition of claim 7, wherein the aluminium salt is a hydroxide (e.g. oxyhydroxide) or a phosphate (e.g. hydroxyphosphate), or a mixture of two or more of said salts.

9. The composition of claim 1, wherein aluminium salt is aluminium hydroxyphosphate and the antigen is an acidic antigen.

10. The composition of claim 1, wherein the concentration of histidine in the composition is between 1 mM and 10 mM.

11. The composition of claim 10, wherein the concentration of histidine is between about 5 mM and about 10 mM.

12. The composition of claim 1, further comprising a sodium salt (e.g. sodium phosphate).

13. The composition of claim 12, wherein the concentration of the sodium salt is between about 2.5 mM and about 5 mM.

14. The composition of claim 1, wherein the pH of the composition is between 6 and 7.

15. The composition of claim 1, further comprising a pharmaceutically acceptable carrier.

16. The composition of claim 1, comprising more than one antigen.

17. The composition of claim 16, wherein more than one of the antigens is adsorbed to an aluminium salt.

18. The composition of claim 16 or claim 17, comprising 2, 3, 4, 5, 6 or 7 of the following:

an antigen from Bordetella pertussis;

a diphtheria antigen;

a tetanus antigen;

an antigen from hepatitis B virus;

a saccharide antigen from Haemophilus influenzae;

inactivated polio virus; and

a saccharide antigen from N. meningitidis serogroup C.

23. A method for raising an immune response in a mammal comprising the step of administering an effective amount of the composition of claim 1.

24. The method of claim 23, wherein the mammal is a human.

25. A process for producing the composition of claim 1, comprising the step of admixing one or more antigens, an aluminium salt and histidine.

26. The process of claim 25, wherein the admixing comprises:

a first step of admixing (i) the aluminium salt and (ii) histidine, to give a histidine/aluminium salt admixture; and

a second step of admixing (i) said histidine/aluminium salt admixture and (ii) one or more antigens.

27. The process of claim 26, wherein the composition is combined with an antigenic composition.

28. A vaccine comprising the composition of claim 1.

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