COMPOSITION

• US 20090081253A1
• Filed: 03/21/2006
• Published: 03/26/2009
• Est. Priority Date: 03/23/2005
• Status: Abandoned Application

• Current Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Original Assignee: Glaxosmithkline Biologicals SA (GlaxoSmithKline PLC)
• Inventors: Stephenne, Jean, Hanon, Emmanuel Jules
• Application Number:
  US11/909,414
• Publication Number:
  US 20090081253A1
• Time in Patent Office: Days
• US Class Current: 424/206.100
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• 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 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• 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: C12N 2760/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2760/16134 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 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention relates to influenza vaccine formulations and vaccination regimes for immunising against various diseases. In particular the invention relates to vaccine formulations comprising an oil-in-water emulsion adjuvant and 3D-MPL, their use in medicine, in particular their use in augmenting immune responses to various antigens, and to methods of preparation, wherein the oil-in-water emulsion comprises a sterol, a metabolisable oil and an emulsifying agent.

Claims

1. An immunogenic composition comprising:

(a) an antigen or antigenic composition;

(b) an oil-in-water emulsion adjuvant; and

(c) 25 vg (w/v) 3D MPL per composition dose, wherein said oil-in-water emulsion comprises a metabolisable oil, a sterol and/or Alpha-tocopherol, and an emulsifying agent, wherein said emulisifying agent is Polyoxyethylene sorbitan monooleate (Tween 80™

).

2. The immunogenic composition according to claim 1, wherein said metabolisable oil is present in an amount of from about 0.5% to About 20% of the total volume of said immunogenic composition.

3. The immunogenic composition according to claim 1, wherein said metabolisable oil is present in an amount of from about 1.0% to about 10% of the total volume of said immunogenic composition.

5. The immunogenic composition as claimed in claims 1, wherein said sterol or alpha-tocopherol is present in an amount of from about 1.0% to about 20% of the total volume of said immunogenic composition.

6. the immunogenic composition as claimed in claim 5, wherein said alpha-tocopherol is present in an amount of from about 1.0% to about 50% of the total volume of said immunogenic composition.

7. The immunogenic composition as claimed in claim 6, wherein the alpha-tocopherol is present in an amount of about 2.5% of the total volume of said immunogenic composition.

8. The immunogenic composition as claimed in claim 1, wherein said emulsifying agent is present at an amount of from about 0.01% to about 5.0% by weight (w/w) of said immunogenic composition.

10. The immunogenic composition as claimed in claim 1, wherein said oil-in-water emulsifying comprises:

abpit 2% to 10% squalene, about 2% to 10% alpha-tocopherol and about 0.3% to 3% polyoxyethylene sorbitan monooleate (Tween 80™

).

11. The immunogenic composition as claimed in claim 1, wherein said oil-in-water emulsion consists:

squalene, alpha-tocopherol, polyoxyethylene sorbitan monooleate (tween 80™

), and PBS.

13. A method of vaccination comprising delivery of an antigen or antigenic composition, 25 μ

g 3D MPL per composition does and an oil-in-water emulsion adjuvant as defined in claim 1 to an individual or population in need thereof.

19. The method according to claim 1, wherein said immunogenic composition comprises an antigen chosen from the group:

an antigen with at least one CD4 T cell epitope and an antigen with at least one B cell epitope.

27. The immunogenic composition according to claim 1, wherein said composition is combined with a pharmaceutically acceptable carrier.

29. The method according to claim 1, wherein said antigen or antigenic preparation is chosen from the group of:

influenza virus, and HPV.

30. The method according to claim 29, wherein said influenza antigen is chosen from the group Of:

a split influenza virus, a whole influenza virus, a sub-unit influenza virus, an Influenza virosome, and an antigenic preparation thereof.

4. (canceled)

9. (canceled)

12. A method of preventing influenza infection in a human and/or a disease associated with exposure of a human to influenza or a pathogen comprising influenza or a variant thereof, said method comprising the step of administering to the human an immunogenic composition comprising:

(a) an antigen or antigenic composition (b) an oil-in-water emulsion adjuvant; and

(c) 25 μ

g (w/v) 3D MPL per composition dose, wherein said oil-in-water emulsion adjuvant comprises a metabolisable oil, a sterol and/or alph-tocopherol, and an emulsifying agent, and wherein said emulsifying agent is polyoxethylene sorbitan monooleate (Tween 80™

).

14. The method according to claim 12, wherein said immunogenic composition induces at least one response in said human chosen from the group of:

i) an improved CD4 T-cell response;

ii) an improved B cell memory response; and

iii) an improved antibody response against said antigen.

16. The method according to claim 12, wherein said immunogenic composition protects said human against infection or disease caused by a pathogen that is a variant of the pathogen from which the antigen in said immunogenic composition is derived.

17. The method according to claim 12, wherein said immunogenic composition protects said human against infection or disease caused by a pathogen that comprises an antigen that is a variant of that antigen in said immunogenic composition.

15. (canceled)

18. (canceled)

20. (canceled)

21. A method of revaccinating a human previously vaccinated with an antigen or antigenic composition, said method comprising the step of administering to said human an immunogenic composition comprising an antigen or antigenic composition thereof, or a fragment or variant thereof,wherein said antigen or antigenic composition for said previous vaccination comprises an antigen or antigenic composition, or a fragment or variant thereof, 25 μ

g (w/v) 3D MPL per compsition dose, and an oil-in-water emulsion adjuvant.

22. The method according to claim 21, wherein the Antigen for revaccination shares common CD4 T-cell epitopes with an antigen or Antigenic compsoition used in said human for a previous vaccination.

23. The method according to claim 21 Wherein said antigen or antigenic composition for revaccination is adjuvanted.

24. The method according to claim 23, wherein the Adjuvant is chosen from the group of:

an oil-in-water emulsion;

3D-MPL;

a Combination of an oil-in-water emulsion adjuvant and 3D-MPL; and

wherein said oil-in-water Emulsion adjuvant comprises a metabolisabie oil, a sterol and/or alpha-tocopherol, And an emulsifying agent, wherein said emulsifying agent is Polyoxyethylene sorbitan monooleate (Tween 80™

).

25. (canceled)

26. A method for preparing an immunogenic composition comprising, said method comprising the step of:

combining an oil-in-water emulsion adjuvant, wherein said adjuvant comprises a metabolisable oil, a sterol and/or alpha-tocopherol and an emulsifying agent, and wherein said emulsifying agent is polyoxyethylene sorbitan monooleate (Tween 80™

) with an antigen or antigenic composition and 25 μ

g (w/v) 3D-MPL per composition dose.

28. A method for protecting a human against a pathogen, said method comprising the step of administering to said human an immunogenic composition that comprises:

(a) an antigen derived from said pathogen;

(b) an oil-in-water emuslsion adjuvant, wherein said adjuvant comprises a metabolisable oil, a sterol and/or alpha-tocopherol, and an emulisifying agent, and wherein said emulsifying agent is polyoxyethylene sorbitan monooleate (Tween 80™

); and

(c) 25 μ

g (w/v) 3D MPL per composition dose.

31-34. -34. (canceled)