Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy.
BACKGROUND
Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods.


OBJECTIVE
Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens.


METHODS
Mice were sensitized to pollen (n=18), house dust mite (HDM, n=24), ovalbumin (OVA, n=18) or peanut (n=18), and allocated to four groups: EPIT, SCIT, not treated (NT) and control. Specific Ig (sIg)E, sIgG1 and sIgG2a were monitored. After 8 weeks of treatment, plethysmography was performed after aerosol provocation with appropriate allergens.


RESULTS
At the highest doses of methacholine, pause enhancement (Penh) values were significantly decreased in the EPIT group vs. the sensitized NT groups (7.5 vs. 12.3 - pollen, 7.6 vs. 8.9 - HDM, 11.5 vs. 14.5 - OVA, 7.6 vs. 12.8 - peanut, respectively) (P<0.05). With all the allergens tested, Penh values were similar in SCIT, EPIT and control. IgG2a for pollen, HDM, OVA and peanuts were significantly increased in the EPIT group vs. NT: 0.97 vs. 0.42 microg/mL, 2.5 vs. 0.46 microg/mL, 0.39 vs. 0.05 microg/mL and 15.0 vs. 5.5 microg/mL, respectively (P<0.05). There were no significant differences between EPIT and SCIT groups. The IgE/IgG2a ratio decreased significantly in the EPIT group for the four allergens from 70 to 58 (pollen), 175 to 26 (HDM), 5433 to 120 (OVA) and 49 to 6 (peanut), respectively (P<0.05).


CONCLUSIONS
In mice sensitized to the four allergens tested, EPIT was as efficacious as SCIT, considered as the reference immunotherapy. These first results have to be confirmed by clinical studies.
Mondoulet
L
L
DBV Technologies, Paris, France. lucie.mondoulet@dbv-technologies.com <lucie.mondoulet@dbv-technologies.com>
Dioszeghy
V
V
Ligouis
M
M
Dhelft
V
V
Dupont
C
C
Benhamou
P-H
PH
D000818:Animals; D010367:Arachis / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D005512:Food Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000628:therapy; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D021183:Peanut Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000628:therapy; D011058:Pollen / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000628:therapy; D012867:Skin / Q000276:immunology*; D016896:Treatment Outcome
D010047:Ovalbumin