Use of penetration enhancers and barrier disruption agents to enhance the transcutaneous immune response

• US 6,797,276 B1
• Filed: 02/25/1999
• Issued: 09/28/2004
• Est. Priority Date: 11/14/1996
• Status: Expired due to Term

• Current Assignee: US Department of The Army (Government of the United States of America)
• 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): EWOLDT, GERALD R
• Application Number:
  US09/257,188
• Time in Patent Office: 2,042 Days
• Field of Search: 424/234.1, 424/278.1, 424/283.1, 424/184.1, 424/204.1, 424/206.1, 424/241.1, 424/265.1, 424/274.1
• US Class Current: 424/278.1
• 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 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55511 Organic 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 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 31/739 Lipopolysaccharides
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/008 Leishmania 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 39/102 Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
• CPC Class Codes: A61K 39/107 Vibrio
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 : Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/205 : Rhabdoviridae, e.g. rabies virus
• CPC Class Codes: A61K 39/39 : characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 47/08 : containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/10 : Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 : Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0014 : Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• 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: 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 2760/16034 : 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

A transcutaneous immunization system where the topical application of an adjuvant and an antigen or nucleic acid encoding for an antigen, to intact skin induces a ystemic or mucosol antibody response. The immune response so elicited can be enhanced by physical or chemical skin penetration enhancement.

Claims

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

a. pretreating an are of the skin of said subject; and

b. applying a formulation to said pretreated area, wherein said formulation comprises;

1) at least one antigen sufficient to induce an antigen-specific immune response against a pathogen,

2) at least one adjuvant present in an amount effective to induce said immune response to said at least one antigen; and

,

3) a pharmaceutically acceptable carrier, wherein said pretreating enhances skin penetration by said formulation and thereby induces said immune response,

wherein said pretreating is selected from the group consisting of direct application to said skin, rubbing, swabbing, applying a depilatory agent, applying a keratinolytic formulation, shaving, tape stripping, abrading and a combination thereof.

2. The method of claim 1, wherein said swabbing comprises a swab comprising a material selected from the group consisting of cotton, nylon, wool and combinations thereof.

3. The method of claim 2, wherein said swab further comprises an alcohol, a composition comprising an alcohol, acetone, a composition comprising acetone, a detergent or a detergent solution.

4. The method of claim 1 wherein said pretreating comprises applying a detergent or a detergent solution to said pretreated area.

5. The method of claim 1, wherein said antigen is derived from a pathogen selected from the group consisting of virus, bacteria, fungus and parasite.

6. The method of claim 1, wherein said antigen is derived from an influenza virus.

7. The method of claim 6, wherein said antigen is hemaglutinin A.

8. The method of claim 1, wherein said antigen is derived from a bacteria.

9. The method of claim 8, wherein said antigen is E. coli heat-labile entertoxin (LT).

10. The method of claim 1, further comprising a carrier, wherein said carrier is a patch.

11. The method of claim 10, wherein said patch is selected from the group consisting of an occlusive dressing, a nonocclusive dressing, a hydrogel dressing and a reservoir dressing.