Device, Method, and system for neural modulation as vaccine adjuvant in a vertebrate subject

• US 20110150924A1
• Filed: 12/22/2009
• Published: 06/23/2011
• Est. Priority Date: 12/22/2009
• Status: Active Grant

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Dowling, Joshua L., Ishikawa, Muriel Y., Myhrvold, Nathan P., Tegreene, Clarence T., Goodall, Eleanor V., Wood, Lowell L. JR., Hyde, Roderick A., Kare, Jordin T., Sweeney, Elizabeth A., Wood, Victoria Y.H., Leuthardt, Eric C., Della Rocca, Gregory J., Malaska, Stephen L., Santiago, Paul, Stewart, Todd J.
• Granted Patent: US 8,321,012 B2
• Time in Patent Office: Days
• US Class Current: 424/204.1
• CPC Class Codes: A61F 7/00 Heating or cooling appliances for medical or therapeutic treatment of the human body heating or cooling means in connection with bedsteads or mattresses A47C21/00 ; massage, therapeutic baths A61H; hyperthermia using electric or magnetic fields or ultrasound A61N; electric heating elements H05B
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61N 1/303 Constructional details electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• CPC Class Codes: A61N 1/36121 Production of neurotransmitters; Modulation of genes expression
• CPC Class Codes: A61N 2/00 Magnetotherapy
• CPC Class Codes: A61N 2/002 in combination with another treatment
• CPC Class Codes: A61N 2/006 for magnetic stimulation of nerve tissue
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: A61N 5/0622 Optical stimulation for exciting neural tissue
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A method for enhancing an immune response in a vertebrate subject is described. The method includes providing at least one energy stimulus configured to modulate one or more nervous system components of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are provided in a combination and in a temporal sequence sufficient to enhance an immune response in the vertebrate subject.

Claims

1. A method for enhancing an immune response to one or more immunogen in a vertebrate subject, comprising:

providing at least one energy stimulus configured to modulate one or more nervous system components of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are provided in a combination and in a temporal sequence sufficient to enhance the immune response in the vertebrate subject.

2. The method of claim 1, wherein the at least one energy stimulus includes one or more of electrical energy, magnetic energy, electromagnetic energy, ultrasonic energy, acoustic energy, mechanical energy, or thermal energy.

3. The method of claim 2, wherein the at least one energy stimulus includes at least one energy characteristic having one or more of waveform, frequency, amplitude, or duration.

4. The method of claim 1, wherein the one or more immunogen includes one or more of a bacterial antigen, a viral antigen, a fungal antigen, or a parasital antigen.

5. The method of claim 1, wherein the one or more immunogen includes a tumor antigen.

6. The method of claim 1, wherein the one or more immunogen includes one or more of a polypeptide, a lipid, a carbohydrate, a lipopolysaccharide, a nucleic acid, a peptide mimetic, a viral antigen, a bacterial antigen, a carcinoembryonic antigen, a mucin, a glycosphingolipid, a genetically engineered antigen, an antigen designed in silico, or a synthetic antigen.

7. The method of claim 1, wherein the at least one energy stimulus and immunogen are provided simultaneously.

8. The method of claim 1, wherein the at least one energy stimulus is provided prior to administering the immunogen.

9. The method of claim 1, wherein the immunogen is provided prior to providing the at least one energy stimulus.

10. The method of claim 1, wherein the at least one energy stimulus and the immunogen are provided at one administration site.

11. The method of claim 1, wherein the at least one energy stimulus and the immunogen are provided at different administration sites.

12. The method of claim 1, wherein the at least one energy stimulus and the immunogen are provided as a booster immunization.

13. The method of claim 1, further including providing one or more transducer configured to direct the at least one energy stimulus to a tissue.

14. The method of claim 1, further including providing an energy generator to provide the at least one energy stimulus.

15. The method of claim 14, wherein the energy generator includes one or more transducer configured to direct the at least one energy stimulus to a tissue.

16. The method of claim 1, further including providing the at least one energy stimulus to a tissue near an immunogen administration site.

17. The method of claim 1, wherein modulating the one or more nervous system components includes stimulating the one or more nervous system components in the vertebrate subject.

18. The method of claim 1, wherein modulating the one or more nervous system components includes inhibiting the one or more nervous system component in the vertebrate subject.

19. The method of claim 1, wherein modulating the one or more nervous system components includes modulating release of a neurotransmitter.

20. The method of claim 19, wherein the neurotransmitter modulates one or more nerve impulses in the vertebrate subject.

21. The method of claim 19, wherein modulating release includes stimulating release of the neurotransmitter.

22. The method of claim 19, wherein modulating release includes inhibiting release of the neurotransmitter.

23. The method of claim 19, wherein the neurotransmitter modulates a function of one or more cells of the vertebrate subject.

24. The method of claim 23, wherein the one or more cells include nerve cells.

25. The method of claim 24, wherein the one or more cells include the same cells that released the neurotransmitter.

26. The method of claim 23, wherein the one or more cells include a non-nervous system cell type.

27. The method of claim 19, wherein the neurotransmitter includes a glucocorticoid, norepinephrine, noradrenalin, neuropeptide Y, substance P, CGRP, NGF or VIP.

28. The method of claim 1, wherein the at least one energy stimulus is provided to the vertebrate subject within a region of an immunogen administration site.

29. The method of claim 1, wherein the at least one energy stimulus is provided to a tissue of the vertebrate subject in the vicinity of a lymph node, wherein the lymph node is located within a region of an immunogen administration site of the vertebrate subject.

30. The method of claim 1, wherein the at least one energy stimulus is configured to elicit a systemic neurogenic response in the vertebrate subject.

31. The method of claim 1, wherein the at least one energy stimulus is configured to elicit a local neurogenic response in the vertebrate subject.

32. The method of claim 1, wherein the at least one energy stimulus is provided to a tissue of the vertebrate subject and configured to enhance a response involving a lymphoid organ, thymus, spleen, bone marrow, peritoneum, mucosal tissue, or a portion of a digestive tract.

33. The method of claim 3, wherein an application pattern of the at least one energy stimulus includes one or more of a cyclical pattern, intermittent pattern, repetitive pattern, random pattern, or non-random pattern.

34. The method of claim 33, wherein providing the application pattern includes applying the pattern at one or more sites.

35. The method of claim 1, wherein enhancing the immune response in the vertebrate subject includes enhancing an immune response against an infectious disease, a prion disease, a neoplastic disease, a heart disease, a respiratory disease, an autoimmune disease, a hyperimmune disease, or an allergic response.

36. The method of claim 1, wherein enhancing the immune response in the vertebrate subject includes enhancing an immune response to prevent an infectious disease, a prion disease, a neoplastic disease, a heart disease, a respiratory disease, an autoimmune disease, a hyperimmune disease, or an allergic response.

37. The method of claim 1, wherein the vertebrate subject includes a mammal, an avian, a reptile, an amphibian, an osteichthye, or a chondrichthyes.

39. The method of claim 1, wherein providing the one or more immunogen includes delivering the one or more immunogen to the vertebrate subject using one or more of a microneedle, a microfine lance, a microfine cannula, a microinjector, a jet fluid injector, a high pressure jet fluid injector, or a tissue implant.

40. The method of claim 1, wherein providing the one or more immunogen includes delivering the one or more immunogen to the vertebrate subject using one or more of iontophoresis, microdialysis, ultrafiltration, electromagnetics, osmosis, electroosmosis, sonophoresis, electroporation, thermal poration, microporation, skin permeabilization, or laser.

38. (canceled)

41. (canceled)

42. A method for enhancing an immune response to an infectious agent in a vertebrate subject comprising:

providing at least one energy stimulus configured to modulate one or more nervous system components of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are provided in a combination and in a temporal sequence sufficient to enhance the immune response in the vertebrate subject.

43. The method of claim 42, wherein the at least one energy stimulus includes one or more of electrical energy, magnetic energy, electromagnetic energy, ultrasonic energy, acoustic energy, mechanical energy, or thermal energy.

44. The method of claim 43, wherein the at least one energy stimulus includes at least one energy characteristic having one or more of waveform, frequency, amplitude, or duration.

45. The method of claim 42, wherein the one or more immunogen includes one or more of a bacterial antigen, a viral antigen, a fungal antigen, or a parasital antigen.

46. The method of claim 42, wherein the one or more immunogen includes one or more of a polypeptide, a lipid, a carbohydrate, a lipopolysaccharide, a nucleic acid, a peptide mimetic, a viral antigen, a bacterial antigen, a carcinoembryonic antigen, a mucin, a glycosphingolipid, a genetically engineered antigen, an antigen designed in silico, or a synthetic antigen.

48. The method of claim 42, wherein the at least one energy stimulus and immunogen are provided simultaneously.

49. The method of claim 42, wherein the at least one energy stimulus is provided prior to administering the immunogen.

50. The method of claim 42, wherein the immunogen is provided prior to providing the at least one energy stimulus.

54. The method of claim 42, further including providing one or more transducer configured to direct the at least one energy stimulus to a tissue.

55. The method of claim 42, further including providing an energy generator to provide the at least one energy stimulus.

56. The method of claim 55, wherein the energy generator includes one or more transducer configured to direct the at least one energy stimulus to a tissue.

57. The method of claim 42, further including providing the at least one energy stimulus to a tissue near an immunogen administration site.

58. The method of claim 42, wherein modulating the one or more nervous system components includes stimulating the one or more nervous system components in the vertebrate subject.

59. The method of claim 42, wherein modulating the one or more nervous system components includes inhibiting the one or more nervous system component in the vertebrate subject.

60. The method of claim 42, wherein modulating the one or more nervous system components includes modulating release of a neurotransmitter.

47. (canceled)

51-53. -53. (canceled)

61-207. -207. (canceled)