Adjuvant for transcutaneous immunization

• US 7,037,499 B1
• Filed: 03/12/1999
• Issued: 05/02/2006
• Est. Priority Date: 11/14/1996
• Status: Expired due to Fees

• Current Assignee: Government of the United States of America
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Alving, Carl R., Glenn, Gregory M.
• Primary Examiner(s): EWOLDT, GERALD R
• Application Number:
  US09/266,803
• Time in Patent Office: 2,608 Days
• Field of Search: 424/447, 424/449, 424/450, 424/234.1, 424/236.1, 424/240.1, 424/241.1, 424/261.1
• US Class Current: 424/184.1
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 2039/55527 Interleukins
• CPC Class Codes: A61K 2039/55544 Bacterial toxins
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A transcutaneous immunization system delivers antigen to immune cells without perforation of the skin, and induces an immune response in an animal or human. The system uses an adjuvant, preferably an ADP-ribosylating exotoxin, to induce an antigen-specific immune response (e.g., humoral and/or cellular effectors) after transcutaneous application of a formulation containing antigen and adjuvant to intact skin of the animal or human. The efficiency of immunization may be enhanced by adding hydrating agents (e.g., liposomes), penetration enhancers, or occlusive dressings to the transcutaneous delivery system. This system may allow activation of Langerhans cells in the skin, migration of the Langerhans cells to lymph nodes, and antigen presentation.

Claims

1. A method of inducing an immune response to at least one antigen comprising

applying a formulation to hydrated skin of an organism,

wherein the formulation comprises

(i) at least one antigen which is derived from a pathogen and

(ii) an adjuvant,

wherein an effective amount of the at least one antigen induces the immune response to the at least one antigen in the organism.

2. The method of claim 1, wherein the pathogen is selected from the group consisting of bacterium, virus, fungus and parasite.

3. The method of claim 1, wherein the antigen is selected from the group consisting of carbohydrate, glycolipid, glycoprotein, lipid, protein, lipoprotein, phospholipid, and polypeptide.

4. The method of claim 1, wherein the pathogen is a live or an attenuated live virus and the antigen is expressed by the live or attenuated live virus.

5. The method of claim 2, wherein the bacterium is anthrax.

6. The method of claim 2, wherein the virus is rabies.

7. The method of claim 1, wherein the adjuvant is selected from the group consisting of bacterial DNA, cytokines, chemokines and lipopolysaccharides.

8. The method of claim 1, wherein the adjuvant is an ADP-ribosylating exotoxin or toxoid thereof having adjuvant activity.

9. The method of claim 8, wherein the ADP-ribosylating exotoxin or toxoid thereof is selected from the group consisting of pertussis toxin, a pertussis toxin toxoid having adjuvant activity, cholera toxin (CT), a CT toxoid having adjuvant activity, an E. coli heat-labile enterotoxin (LT), an LT toxoid having adjuvant activity, diphtheria toxin (DT), a DT toxoid having adjuvant activity, Pseudomonas exotoxin A, and a Pseudomonas exotoxin A toxoid having adjuvant activity.

10. The method of claim 1, wherein the adjuvant is an ADP-ribosylating exotoxin B subunit from cholera toxin (CT).

11. The method of claim 1, wherein the adjuvant is selected from the group consisting of an ADP-ribosylating exotoxin in which ADP-ribosyl transferase activity is inactivated;

an ADP-ribosylating exotoxin chemically conjugated to a carbohydrate, polypeptide, glycolipid, or glycoprotein antigen;

an ADP-ribosylating exotoxin subunit chemically conjugated to a carbohydrate, polypeptide, glycolipid, or glycoprotein antigen; and

, an ADP-ribosylating toxoid chemically conjugated to a carbohydrate, polypeptide, glycolipid, or glycoprotein antigen.

12. The method of claim 1, wherein the formulation is a cream or gel or emulsion or ointment or lotion or paste or solution or suspension.

13. The method of claim 1, wherein the formulation is applied with a patch.

14. The method of claim 1, wherein the formulation further comprises a dressing.

15. The method of claim 14, wherein the dressing is occlusive or non-occlusive.

16. The method of claim 7, wherein said cytokine is tumor necrosis factor alpha.