NON-LIVE TRIVALENT INFLUENZA VACCINE FOR ONE-DOSE INTRADERMAL DELIVERY

• US 20070237788A1
• Filed: 06/13/2007
• Published: 10/11/2007
• Est. Priority Date: 02/23/2001
• Status: Active Grant

• Current Assignee: Glaxosmithkline Biologicals SA (GSK plc)
• Original Assignee: Glaxosmithkline Biologicals SA (GSK plc)
• Inventors: VAN HOECKE, Christian, SLAOUI, Moncef, GARCON, Nathalie
• Granted Patent: US 8,557,251 B2
• Time in Patent Office: Days
• US Class Current: 424/209.100
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/55577 Saponins; Quil A; QS21; ISCOMS
• 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: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• 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

Abstract

The invention relates to the use of a trivalent, non-live influenza antigen preparation, particularly a split influenza preparation, in the manufacture of a one-dose influenza vaccine for intradermal delivery. In particular, the invention relates to the use of split influenza preparations wherein the vaccine comprises at least one non-ionic surfactant selected from the group consisting of the octyl- or nonylphenoxy polyoxyethanols (for example the commercially available Triton™ series), polyoxyethylene sorbitan esters (Tween™ series) and polyoxyethylene ethers or esters of general formula (I): HO(CH₂CH₂O)_n-A-R, wherein n is 1-50, A is a bond or —C(O)—, R is C_1-50alkyl or phenyl C_1-50alkyl; and combinations of two or more of these.

Claims

1. A method for inducing a protective immune response in a human population comprising administering intradermally a single dose of a trivalent, non-live influenza vaccine antigen preparation, wherein said protective immune response meets at least one criteria chosen from the group of:

(1) a protection rate of >

70% in adults of 18-60 years old or of >

60% in elderly people of above 60 years old;

(2) a seroconversion rate of >

40% in adults of 18-60 years old or of >

30% in elderly people of above 60 years old; and

(3) a conversion factor of >

2.5 HI titres in adults of 18-60 years old or of >

2.0 HI titres in elderly people of above 60 years old, is obtained for all three influenza strains.

2. The method according to claim 1, wherein the antigen preparation is a split influenza preparation.

3. The method according to claim 1, wherein the influenza antigen is egg-derived.

4. The method according to claim 1, wherein the vaccine comprises at least one non-ionic surfactant selected from the group consisting of an octyl- or nonylphenoxy polyoxyethanol, polyoxyethylene sorbitan ester and a polyoxyethylene ether or ester of general formula (I):

HO(CH₂CH₂O)_n-A-R 

 

(I)

wherein n is 1-50, A is a bond or —

C(O)—

, R is C_1-50 alkyl or phenyl C_1-50 alkyl.

6. The method according to claim 1, wherein the vaccine further comprises a bile acid or cholic acid, or derivative thereof.

7. The method according to claim 1, wherein the vaccine is provided in a dose volume of between about 0.1 and about 0.2 ml.

8. The method according to claim 1, wherein the vaccine is provided with an antigen dose of 1-5 μ

g haemagglutinin per strain of influenza present.

9. The method according claim 1, wherein the vaccine further comprises an adjuvant comprising a combination of cholesterol, a saponin and an LPS derivative.

10. The method according to claim 1, wherein the vaccine is provided in an intradermal delivery device.

12. The method according to claim 1, wherein said influenza vaccine antigen preparation is obtained by a process comprising:

(i) harvesting virus-containing material from a culture;

(ii) clarifying the harvested material to remove non-virus material;

(iii) concentrating the harvested virus;

(iv) separating whole virus from non-virus material;

(v) splitting the whole virus using a suitable splitting agent in a density gradient centrifugation step; and

(vi) filtering the product of step (v) to remove undesired materials.

13. A pharmaceutical kit comprising an intradermal delivery device and influenza vaccine antigen preparation according to claim 1.

18. The method according to claim 7, wherein the cholic acid derivative is sodium deoxycholate.

5. The method according to claim 5, wherein the vaccine comprises a combination of polyoxyethylene sorbitan monooleate (Tween 80) and t-octylphenoxy polyethoxyethanol (Triton X-100).

11. The method according to claim 11, wherein the device is a short needle delivery device.

14. The pharmaceutical kit according to claim 14, wherein the intradermal delivery device is a short needle device.

15. The pharmaceutical kit according to claim 14, wherein the volume of vaccine is between about 0.05 and 0.2 ml.

16. A method for inducing a protective immune response in a human population comprising administering intradermally a single dose of a trivalent, non-live influenza vaccine antigen preparation, wherein said protective immune response meets at least two criteria chosen from the group of:

(1) a protection rate of >

70% in adults of 18-60 years old or of >

60% in elderly people of above 60 years old;

(2) a seroconversion rate of >

40% in adults of 18-60 years old or of >

30% in elderly people of above 60 years old; and

(3) a conversion factor of >

2.5 HI titres in adults of 18-60 years old or of >

2.0 HI titres in elderly people of above 60 years old is obtained for at least two influenza strains.

17. A method for inducing a protective immune response in a human population comprising administering intradermally a single dose of a trivalent, non-live influenza vaccine antigen preparation, wherein said protective immune response, as assessed by:

(1) a protection rate of >

70% in adults of 18-60 years old or of >

60% in elderly people of above 60 years old;

(2) a seroconversion rate of >

40% in adults of 18-60 years old or of >

30% in elderly people of above 60 years old; and

(3) a conversion factor of >

2.5 HI titres in adults of 18-60 years old or of >

2.0 HI titres in elderly people of above 60 years old is obtained for all three influenza strains.