Transcutaneous immunization without heterologous adjuvant

• US 8,911,742 B2
• Filed: 01/12/2012
• Issued: 12/16/2014
• Est. Priority Date: 11/14/1996
• Status: Expired due to Fees

• Current Assignee: Government Of The United states, As Represented By The Secretary of The Office Of The Command Judge Advocate
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Glenn, Gregory M., Alving, Carl R.
• Primary Examiner(s): Kim, Yunsoo
• Application Number:
  US13/348,970
• Publication Number:
  US 20120201845A1
• Time in Patent Office: 1,069 Days
• Field of Search: None
• US Class Current: 424/184.1
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• 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 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/55533 IL-2
• 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 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/008 Leishmania antigens
• CPC Class Codes: A61K 39/015 Hemosporidia antigens, e.g. Plasmodium antigens
• CPC Class Codes: A61K 39/0258 Escherichia
• CPC Class Codes: A61K 39/05 Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium Mycobacterium A61K39/04
• CPC Class Codes: A61K 39/08 Clostridium, e.g. Clostridium tetani
• CPC Class Codes: A61K 39/099 Bordetella
• CPC Class Codes: A61K 39/102 Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
• CPC Class Codes: A61K 39/104 Pseudomonadales, e.g. Pseudomonas
• CPC Class Codes: A61K 39/107 Vibrio
• CPC Class Codes: A61K 39/116 : Polyvalent bacterial antigens
• CPC Class Codes: A61K 39/12 : Viral antigens
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 37/04 : Immunostimulants
• 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 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
• CPC Class Codes: C12N 2760/20134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Transcutaneous immunization can deliver antigen to the immune system through the stratum corneum without physical or chemical penetration to the dermis layer of the skin. This delivery system induces an antigen-specific immune response without the use of a heterologous adjuvant. This system can induce antigen-specific immune effectors after epicutaneous application of a formulation containing one or more antigensImmune responses that provide prophylactic and/or therapeutic treatments are preferred. Antigenic activities in the formulation may be found in the same molecule, two or more different molecules dissociated from each other, or multiple molecules in a complex formed by covalent or non-covalent bonds. For antigens which are proteinaceous, they may be provided in the formulation as a polynucleotide for transcutaneous genetic immunization. Besides simple application of a dry or liquid formulation to the skin, patches and other medical devices may be used to deliver antigen for immunization.

Claims

1. A method for inducing an antigen-specific immune response in a subject comprising:

pretreating an area of the subject'"'"'s skin,

applying a formulation epicutaneously to said pretreated area, wherein said formulation comprises an antigen which comprises a pathogen or is derived from a pathogen and does not include a liposome, wherein said formulation is applied in dry form, and wherein said pretreating enhances skin penetration without perforating the skin'"'"'s dermis layer thereby inducing an antigen-specific immune response in the subject.

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

3. The method of claim 2, wherein the bacterium is Bacillus anthracis.

4. The method of claim 2, wherein the virus is influenza virus.

5. The method of claim 1, wherein the antigen comprises the recombinant protective antigen (rPA) of Bacillus anthracis.

6. The method of claim 1, wherein the antigen comprises influenza virus hemagglutinin.

7. The method of claim 1, wherein the antigen is selected from the group consisting of carbohydrate, a glycolipid, glycoprotein, lipid, lipoprotein, phospholipid, polypeptide, protein, fusion protein, and chemical conjugates thereof.

8. The method of claim 1, wherein the antigen is a nucleic acid.

9. The method of claim 1, wherein the antigen is a multivalent antigen.

10. The method of claim 1, wherein the antigen also acts as an adjuvant.

11. The method of claim 1, wherein the formulation further comprises a pharmaceutically acceptable carrier or vehicle.

12. The method of claim 1, wherein the formulation further comprises at least one additive or a combination of additives.

13. The method of claim 12, wherein the additive is selected from the group consisting of excipients, preservatives and stabilizers.

14. The method of claim 1, wherein the antigen is applied via a patch.

15. The method of claim 1, wherein pretreating comprises applying to the skin a chemical means, a physical means, a mechanical means, a hydration means, or a combination thereof.

16. The method of claim 15, wherein the chemical is an alcohol, an acetone, a detergent, a depilatory agent, a keratinolitic formulation, or a combination thereof.

17. The method of claim 1, wherein pretreating comprises applying a device.

18. The method of claim 17, wherein the device is selected from a group consisting of a tape stripping device, a swab, an emery board, an abrasive pad, a microneedle comprising device, a device comprising a tine disk, a propellant device, an electroporation device, an ultrasound device, and an ionophoresis device.