Method for inducing a systemic immune response to an HIV antigen

• US 6,207,185 B1
• Filed: 10/10/1997
• Issued: 03/27/2001
• Est. Priority Date: 03/22/1996
• Status: Expired due to Term

• Current Assignee: Oral Vaccine Technologies Incorporated
• Original Assignee: Bio-Gene Technology Ltd.
• Inventors: See, Jackie R., See, Darryl M.
• Primary Examiner(s): KISHORE, GOLLAMUDI S
• Application Number:
  US08/948,568
• Time in Patent Office: 1,264 Days
• Field of Search: 424/450, 424/184.1, 424/188.1, 424/193.1, 424/196.11, 424/204.1, 424/207.1, 436/829
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/125 Picornaviridae, e.g. calicivirus
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: C12N 2740/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/32334 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y10S 436/829 Liposomes, e.g. encapsulation

Abstract

A method is provided for inducing a systemic immune response to an antigen selected from inactivated HIV I and HIV II antigens in a mammal. The method comprises orally administering lyophilized multilaminar liposomes containing the antigen. The liposomes have a size of from 20 nm to 20 microns. The antigen-containing liposomes are absorbed in the Peyer'"'"'s patches of the gut. Sufficient antigen-containing liposomes are taken up by macrophages in the Peyer'"'"'s patches to induce a systemic immune response to the antigen.

Claims

1. A method for stimulating a systemic immune response to an antigen selected from the group consisting of inactivated HIV I and HIV II antigens and combinations thereof in a mammal comprising:

providing a lipsomal preparation comprising lyophilized liposomes containing at least one antigen selected from the group consisting of inactivated HIV I and HIV II antigens, wherein the liposomes have at least three different sizes and consist essentially of;

at least 5% by volume, based on the total volume of liposomes in the preparation, small liposomes having a size, before lyophilization, of from about 20 nm to about 1 micron,

at least 5% by volume, based on the total volume of liposomes in the preparation, medium liposomes having a size, before lyophilization, of from about 1 micron to about 3 microns, and

at least 5% by volume, based on the total volume of liposomes in the preparation, large liposomes having a size, before lyophilization, of from about 3 microns to about 20 microns; and

orally administering an effective amount of the liposomal preparation to a mammal,

whereby sufficient antigen containing liposomes are absorbed in the Peyer'"'"'s patches of the gut of the mammal and are taken up by macrophages in the Peyer'"'"'s patches to stimulate a systemic immune response.

2. A method as claimed in claim 1, wherein the liposomes are multi-lamellar before lyophilization.

3. A method as claimed in claim 1, wherein the liposomal preparation is contained within an enterically-coated capsule.

4. A method as claimed in claim 1 wherein the liposomes consist essentially of at least 5% by volume, based on the total volume of liposomes in the preparation, small liposomes having a size, before lyophilization, of from about 20 nm to about 1 micron, at least 10% by volume, based on the total volume of liposomes in the preparation, medium liposomes having a size, before lyophilization, of from about 1 micron to about 3 microns, and at least 20% by volume, based on the total volume of liposomes in the preparation, large liposomes having a size, before lyphilization, of from about 3 microns to about 20 microns.

5. A method as claimed in claim 1 wherein the liposomes comprise about 10% by volume, based on the total volume of liposomes in the preparation, small liposomes having a size, before lyophilization, of from about 20 nm to about 1 micron, about 25% by volume, based on the total volume of liposomes in the preparation, medium liposomes having a size, before lyophilization, of from about 1 micron to about 3 microns, and about 65% by volume, based on the total volume of liposomes in the preparation, large liposomes having a size, before lyopilization, of from about 3 microns to about 20 microns.

6. A method as claimed in claim 1 wherein the liposomes comprise at least two different antigens.

14. A method according to claim 1, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 10 microns.

15. A method according to claim 1, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 5 microns.

16. A method according to claim 1, wherein the small liposomes have a size, before lyophilization, of about 1 micron.

17. A method according to claim 1, wherein the medium liposomes have a size, before lyophilization, of about 2 microns.

18. A method according to claim 1, wherein the large liposomes have a size, before lyophilization, of about 10 microns.

19. A method according to claim 1, wherein the small liposomes have a size, before lyophilization, of about 1 micron, the medium liposomes have a size, before lyophilization, of about 2 microns, and the large liposomes have a size, before lyophilization, of about 10 microns.

20. A method according to claim 4, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 10 microns.

21. A method according to claim 4 wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 5 microns.

22. A method according to claim 4, wherein the small liposomes have a size, before lyophilization, of about 1 micron.

23. A method according to claim 4, wherein the medium liposomes have a size, before lyophilization, of about 2 microns.

24. A method according to claim 4, wherein the large liposomes have a size, before lyophilization, of about 10 microns.

25. A method according to claim 4, wherein the small liposomes have a size, before lyophilization, of about 1 micron, the medium liposomes have a size, before lyophilization, of about 2 microns, and the large liposomes have a size, before lyophilization, of about 10 microns.

26. A method according to claim 5, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 10 microns.

27. A method according to claim 5, wherein the large liposomes have a size, before lyphilization, of from about 3 microns to about 5 microns.

28. A method according to claim 5, wherein the small liposomes have a size, before liphilization, of about 1 micron.

29. A method according to claim 5, wherein the medium liposomes have a size, before lyophilization, of about 2 microns.

30. A method according to claim 5, wherein the large liposomes have a size, before lyophilization, of about 10 microns.

31. A method according to claim 5, wherein the small liposomes have a size, before lyophilization, of about 1 micron, the medium liposomes have a size, before lyophilization, of about 2 microns, and the large liposomes have a size, before lyophilization, of about 10 microns.

50. A method according to claim 1 wherein the antigen containing liposomes are capable of being absorbed in the Peyer'"'"'s patches of the gut of the mammal and are capable of being taken up by macrophages in the Peyer'"'"'s patches to stimulate a systemic immune response without the presence of an adjuvant.

51. A method according to claim 1 wherein the antigen containing liposomes are capable of being absorbed in the Peyer'"'"'s patches of the gut of the mammal and are capable of being taken up by macrophages in the Peyer'"'"'s patches to stimulate a systemic immune response without generating a typical adjuvant effect.

7. A preparation for oral administration to a mammal capable of stimulating a systemic immune response to at least one antigen selected from the group consisting of inactivated HIV I and HIV II antigens, said preparation comprising an effective amount of lyophilized antigen-containing liposomes, wherein the liposomes have at least three different sizes, before lyophilization, and consist essentially of:

at least 5% by volume, based on the total volume of liposomes in the preparation, small liposomes having a size, before lyophilization, of from about 20 nm to about 1 micron,

at least 5% by volume, based on the total volume of liposomes in the preparation, medium liposomes having a size, before lyophilization, of from about 1 micron to about 3 microns, and

at least 5% by volume, based on the total volume of liposomes in the preparation, large liposomes having a size, before lyphilization, of from about 3 microns to about 20 microns.

8. A preparation as claimed in claim 7 wherein the liposomes are multi-lamellar before lyophilization.

9. A preparation as claimed in claim 7 wherein the liposome preparation is contained within an enterically-coated capsule.

10. A preparation as claimed in claim 7 wherein the liposomes comprise small, medium and large liposomes.

11. A preparation as claimed in claim 7 wherein the liposomes consist essentially of at least 5% by volume, based on the total volume of liposomes in the preparation, small liposomes having a size, before lyophilization, of from about 20 nm to about 1 micron, at least 10% by volume, based on the total of liposomes in the preparation, medium liposomes having a size, before lyophilization, of from about 1 micron to about 3 microns, and at least 20% by volume, based on the total volume of liposomes in the preparation, large liposomes having a size, before lyophilization, of from about 3 microns to about 20 microns.

12. A preparation as claimed in claim 7 wherein the liposomes consist essentially of about 10% by volume, based on the total volume of liposomes in the prepartion, small liposomes having a size, before lyophilization, of from about 20 nm to about 1 micron, about 25% by volume, based on the total volume of liposomes in the preparation, medium liposomes having a size, before lyophilization, of from about 1 micron to about 3 microns, and about 65% by volume, based on the total volume of liposomes in the preparation, large liposomes having a size, before lyophilization, of from about 3 microns to about 20 microns.

13. A preparation as claimed in claim 7 wherein the liposomes comprise at least two different antigens.

32. A prepairation according to claim 7, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 10 microns.

33. A preparation according to claim 7, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 5 microns.

34. A preparation according to claim 7, wherein the small liposomes have a size, before lyophilization, of about 1 micron.

35. A preparation according to claim 7, wherein the medium liposomes have a size, before lyophilization, of about 2 microns.

36. A preparation according to claim 7, wherein the large liposomes have a size, before lyophilization, of about 10 microns.

37. A preparation according to claim 7, wherein the small liposomes have a size, before lyophilization, of about 1 micron, the medium liposomes have a size, before lyophilization, of about 2 microns and the large liposomes have a sizes before lyophilization, of about 10 microns.

38. A preparation according to claim 11, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 10 microns.

39. A preparation according to claim 11, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 5 microns.

40. A preparation according to claim 11, wherein the small liposomes have a size, before lyophilization, of about 1 micron.

41. A preparation according to claim 11, wherein the medium liposomes have a size, before lyophilization, of about 2 microns.

42. A preparation according to claim 11, wherein the large liposomes have a size, before lyophilization, of about 10 microns.

43. A preparation according to claim 11, wherein the small liposomes have a size, before lyophilization, of about 1 micron, the medium liposomes have a size, before lyophilization, of about 2 microns, and the large liposomes have a size, before lyophilization, of about 10 microns.

44. A preparation according to claim 12, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 10 microns.

45. A preparation according to claim 12, wherein the large liposomes have a size, before lyophilization, of from about 3 microns to about 5 microns.

46. A preparation according to claim 12, wherein the small liposomes have a size, before lyophilization, of about 1 micron.

47. A preparation according to claim 12, wherein the medium liposomes have a size, before lyophilization, of about 2 microns.

48. A preparation according to claim 12, wherein the large liposomes have a size, before lyophilization, of about 10 microns.

49. A preparation according to claim 12, wherein the small liposomes have a size, before lyophilization, of about 1 micron, the medium liposomes have a size, before lyophilization, of about 2 microns, and the large liposomes have a size, before lyophilization, of about 10 microns.