Intranasal or inhalational administration of virosomes

Abstract

The present invention provides a composition of influenza virosomes comprising reconstituted envelopes of said virus, wherein the viral envelopes are entirely derived from influenza viral particles, wherein no lipid is added from an external source to the reconstituted virosomes, wherein the virosomes comprise the influenza antigens haemagglutinin and/or neuraminidase or derivatives thereof, wherein no separate adjuvant and/or immune stimulator is added to the composition, and wherein the composition is for intranasal or inhalational administration, which composition is characterized in that a single intranasal or inhalational administration to a human being is sufficient for the induction of a systemic immune response and/or a local immune response and/or a cytotoxic lymphocytes response against said influenza antigens, which systemic response is in accordance with the CHMP criteria for influenza vaccine, and wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 30 μg. The invention also provides the use of reconstituted influenza virosomes for the manufacture of said composition, and accordingly manufactured vaccine formulations.

Description

Claims

1. A composition comprising influenza virosomes comprising reconstituted envelopes of one or more influenza strains, wherein the viral envelopes are derived entirely from influenza viral particles,wherein no lipid from an external source is added to the reconstituted virosomes,wherein the virosomes comprise the influenza antigen haemagglutinin, andwherein no separate adjuvant, immune stimulator, or adjuvant and immune stimulator is added to the composition.

2. The composition according to claim 1, wherein the dose of haemagglutinin per viral strain is lower than or equal to 30 μg.

3-5. (canceled)

6. The composition according to claim 2, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 25 μg.

7. The composition according to claim 2, wherein the dose of haemagglutinin per viral strain intranasal or inhalational administration is lower than or equal to 20 μg.

8. The composition according to claim 2, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 15 μg.

9. The composition according to claim 2, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 10 μg.

10. The composition according to claim 2, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 5 μg.

11. The composition according to claim 1, wherein the composition is a vaccine formulation comprising a pharmaceutical carrier for intranasal or inhalational administration.

12. A method of inducing an immune response against one or more influenza strains, comprising administering to a human being a single intranasal or inhalational dose of a composition comprising influenza virosomes, wherein the virosomes comprise reconstituted influenza virus envelopes,wherein the viral envelopes are derived entirely from influenza viral particles,wherein no lipid from an external source is added to the reconstituted virosomes,wherein the virosomes comprise the influenza antigen haemagglutinin, andwherein no separate adjuvant, immune stimulator, or adjuvant and immune stimulator is added to the composition.

13. The method according to claim 12, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 30 μg.

14. The method according to claim 12, wherein the single intranasal or inhalational administration of the composition induces a cytotoxic lymphocytes response.

15. The method according to claim 12, wherein the immune response is in accordance with the CHMP criteria for influenza vaccine.

16. The method according to claim 15, wherein the immune response provides one or more of a seroprotection rate of >70% for adults, a seroprotection rate of >60% for elderly, a seroconversion rate of >40% for adults. a seroconversion rate of >30% for elderly, a mean fold increase of >2.5 for adults, or a mean fold increase of >2.0 for elderly.

17. The method according to claim 13, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 25 μg.

18. The method according to claim 13, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 20 μg.

19. The method according to claim 13, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 15 μg.

20. The method according to claim 13, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 10 μg.

21. The method according to claim 13, wherein the dose of haemagglutinin per viral strain per intranasal or inhalational administration is lower than or equal to 5 μg.

22. (canceled)

23. A vaccine formulation comprising a composition of influenza virosomes, wherein the virosomes comprise reconstituted influenza virus envelopes from one or more influenza strains,wherein the viral envelopes are entirely derived from influenza viral particles,wherein no lipid from an external source is added to the reconstituted virosomes,wherein the virosomes comprise the influenza antigen haemagglutinin,wherein no separate adjuvant, immune stimulator, or adjuvant and immune stimulator is added to the composition,wherein the vaccine is designed for a single intranasal or inhalational administration to a human being, andwherein the dose of haemagglutinin per viral strain per single intranasal or inhalational administration is lower than or equal to 30 μg.

24. The vaccine formulation according to claim 23, wherein the dose of haemagglutinin per viral strain per single intranasal or inhalational administration is lower than or equal to 25 μg.

25. The vaccine formulation according to claim 23, wherein the dose of haemagglutinin per viral strain per single intranasal or inhalational administration is lower than or equal to 20 μg.

26. The vaccine formulation according to claim 23, wherein the dose of haemagglutinin per viral strain per single intranasal or inhalational administration is lower than or equal to 15 μg.

27. The vaccine formulation according to claim 23, wherein the dose of haemagglutinin per viral strain per single intranasal or inhalational administration is lower than or equal to 10 μg.

28. The vaccine formulation according to claim 23, wherein the dose of haemagglutinin per viral strain per single intranasal or inhalational administration is lower than or equal to 5 μg.

29-30. (canceled)

31. The vaccine formulation according to claim 23, wherein a single intranasal or inhalational administration of the formulation produces one or more of a seroprotection rate of >70% for adults, a seroprotection rate of >60% for elderly, a seroconversion rate of >40% for adults, a seroconversion rate of >30% for elderly, a mean fold increase of >2.5 for adults, or a mean fold increase of >2.0 for elderly.

32. A device for intranasal or inhalational administration comprising the vaccine formulation according to claim 23 and a mechanism for aerosolization of the vaccine.

33. The device according to claim 32, wherein the device contains a quantity of vaccine formulation for a single intranasal or inhalational administration.

34. The device according to claim 33, wherein the device is disposable.