Allergen desensitization method
Inventors
Dupont, Christophe • Benhamou, Pierre-Henri • Dupont, Bertrand
Assignees
Assistance Publique Hopitaux de Paris APHP • DBV Technologies SA • Universite Paris Cite
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Publication Number
US-10272151-B2
Publication Date
2019-04-30
Expiration Date
Abstract
The present application relates to a method for desensitization of allergic patients. More specifically it relates to an epicutaneous desensitization method, applicable to any type of allergens and of patients. The method of the invention is essentially non-invasive and does not require the use of adjuvants. Further, it may be easily applied and monitored by the actual patient.
Core Innovation
The invention relates to a method for epicutaneous desensitization of a subject allergic to egg. The method comprises determining a dose of an egg allergen which causes an immune reaction on the skin of the subject upon epicutaneous application, and epicutaneously exposing the subject to the egg allergen by applying the determined dose onto an intact region of skin. The exposure generates the immune reaction on the skin without an adjuvant, and the application is conducted using a cutaneous occlusive device configured to ensure contact between the allergen and the region of skin.
The method further requires repeatedly applying the egg allergen, without an adjuvant, to an intact region of the skin of the subject. The repeatedly applied dose is adapted by dose, frequency, or application time to sustain the immune reaction, and the exposure and the sustained reaction lead to desensitization of the subject. The described approach explicitly uses an occlusive device and specifies that the dose of egg allergen is comprised between 0.1 and 1,000 d-g/cmb2 of a surface area of the device.
The sustained cutaneous inflammatory response is monitored and evaluated, and the administration parameters are adapted to maintain an inflammation profile that becomes tolerogenic. The tolerogenic shift is characterized as an immune response modulation leading to immune tolerance, including reduced cutaneous reactivity and an increased tolerance threshold. The described content also characterizes immune timing effects on the inflammatory nature and links the approach to immune-cell interactions associated with the skin immune reaction.
Claims Coverage
The independent claim set in the provided material centers on an epicutaneous desensitization method for a subject allergic to egg, with three inventive features: determining an egg-allergen dose that causes an immune reaction on intact skin without an adjuvant, repeatedly applying that dose via a cutaneous occlusive device while sustaining the immune reaction to achieve desensitization, and specifying a dose-per-device-surface-area range.
Determining an egg allergen dose to cause skin immune reaction without an adjuvant
Determining a dose of an egg allergen which causes an immune reaction on the skin of the subject upon epicutaneous application, and epicutaneously exposing the subject to the egg allergen by applying said dose onto an intact region of skin without an adjuvant.
Repeated epicutaneous exposure with dose, frequency, or application time adapted to sustain immune reaction leading to desensitization
Repeatedly applying the egg allergen, without an adjuvant, to an intact region of the skin at a dose, frequency or for an application time adapted to sustain the immune reaction, such that the exposure and sustained reaction lead to desensitization of the subject.
Cutaneous occlusive device ensuring allergen-skin contact with specified dose per device surface area
Applying the egg allergen by a cutaneous occlusive device configured to ensure contact between the allergen and the region of skin, wherein the dose of egg allergen is comprised between 0.1 and 1,000 d-g/cmb2 of a surface area of the device.
Across the provided independent claim material, the inventive concept is epicutaneous desensitization without an adjuvant by determining an egg-allergen dose that elicits a skin immune reaction on intact skin, then repeatedly applying the allergen using a cutaneous occlusive device while adapting dose, frequency, or application time to sustain the immune reaction, with desensitization resulting.
Stated Advantages
Avoiding adjuvants while generating and sustaining a cutaneous immune reaction that leads to desensitization.
Increasing tolerance threshold and reducing cutaneous reactivity as part of achieving immune tolerance.
Providing an epicutaneous, non-invasive desensitization approach using repeated application to intact skin.
Documented Applications
Epicutaneous desensitization of a subject allergic to egg, including a pediatric cow-milk case described as increasing a tolerance threshold correlated to a monitored inflammatory reaction.
Characterization in animal models described as reducing bronchial hyperreactivity in pollen and ovalbumin mouse models.
Groundnut model comparisons described as showing reduced IgE and increased IgG2a with lower histamine release compared in relation to intradermal route.
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