Use of skin penetration enhancers and barrier disruption agents to enhance transcutaneous immune response induced by an adjuvant
申请(专利)号:
EP20030007949
申请日期:
02/25/1999
公开/公告号:
EP1356823
公开/公告日期:
01/02/2013
申请(专利权)人:
THE GOVERNMENT OF THE UNITED STATES, as represented by THE SECRETARY OF THE ARMY c/o Medical Research & Materiel Command (504 Scott Street, Fort Detrick, MD 21702, US)
被引量:
摘要:
1. A formulation comprising an adjuvant for use in the potentiation of an immune response in a subjectwherein said immune response is induced by a separate antigen-containing formulation to be administered by a process selected from the group consisting of intramuscular injection, oral administration, nasal administration and rectal administration;wherein said adjuvant-containing formulation is to be administered to an area of the subject's skin that is pretreated by physical or mechanical disruption of the stratum corneum, which pretreatment does not perforate the skin;wherein the antigen is at least partially purified in cell-free form and selected from the group consisting of a carbohydrate, a glycolipid, a glycoprotein, a lipid, a lipoprotein, a phospholipid and a polypeptide; andwherein said pretreatment and/or said adjuvant-containing formulation is able to activate Langerhans cells. 2. The formulation according to claim 1, wherein said adjuvant-containing formulation is applied as a patch. 3. The formulation according to any of claims 1 or 2, wherein said adjuvant-containing formulation comprises bacterial DNA, a CpG motif, a lipopolysaccharide, a cytokine, a chemokines, tumor necrosis factor alpha, an ADP-ribosylating exotoxin, a genetically altered toxin, or a toxoid or subunit thereof. 4. The formulation according to any one of claims 1 to 3, wherein said antigen-containing formulation and said adjuvant-containing formulation are to be administered within a short interval of time. 5. The formulation according to any one of claims 1 to 4, wherein said physical or mechanical disruption of the stratum corneum comprises use of tape stripping, alcohol swabbing, microneedles that penetrate the outer surface of the skin or abrasives that remove the outer layer of the skin. 6. The formulation according to claim 5, wherein said abrasive is an emery board or a swab made of cotton, nylon, rayon, or polyethylene. 7. The formulation according to any one of claims 1 to 5, wherein said activation of Langerhans cells is expression of increased levels of MHC Class I and Class II antigens and costimulatory molecules. 8. The formulation according to claim 7, wherein said activation of Langerhans cells is expression of increased levels of MHC Class II antigens and CD83 (B7-2), and further decreased levels of E-cadherin
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