Sublingual Omp16-driven redirection of the allergic intestinal response in a pre-clinical model of food allergy

ORSINI DELGADO MARIA LUCIA; RIZZO GASTON; CARLOS A. FOSSATI; PASQUEVICH KARINA; CASSATARO JULIANA; SMALDINI PAOLA; DOCENA GUILLERMO

CLINICAL AND EXPERIMENTAL ALLERGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020

0954-7894

Background: IgE-mediated food allergy remains a significant and growing worldwideproblem. Sublingual immunotherapy (SLIT) shows an excellent safety profile for foodallergy, but the clinical efficacy needs to be improved. This study assessed the effectsof the Toll-like receptor 4 agonist outer membrane protein (Omp) 16 from Brucellaabortus combined with cow´s milk proteins (CMP) through the sublingual route tomodulate cow's milk allergy in an experimental model.Methods: Mice sensitized with cholera toxin and CMP were orally challenged withthe allergen to elicit hypersensitivity reactions. Then, mice were treated with a verylow amount of CMP along with Omp16 as a mucosal adjuvant, and finally, animalswere re-exposed to CMP. Systemic and mucosal immune parameters were assessedin vivo and in vitro.Results: We found that the sublingual administration of Omp16 + CMP induced abuccal Th1 immune response that modulated the intestinal allergic response with thesuppression of symptoms, reduction of IgE and IL-5, and up-regulation of IgG2a andIFN-γ. The adoptive transfer of submandibular IFN-γ-producing α4β7+CD4+ and CD8+cells conferred protection against allergic sensitization. The use of Omp16 + CMPpromoted enhanced protection compared to CMP alone.Conclusion: In conclusion, Omp16 represents a promising mucosal adjuvant that canbe used to improve the clinical and immune efficacy of SLIT for food allergy.