Development of a tolerogenic allergen-specific immunotherapy based on the biological cross-reactivity between cow's milk and soybean

CANDREVA, ÁNGELA, CURCIARELLO, RENATA; PAOLA SMALDINI, M. LUCIA ORSINI DELGADO, PETRUCCELLI CV NORMALIZADO V. 5.07 SILVANA Y DOCENA GUILLERMO

Los Cocos, Córdoba.

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

Cow´s milk allergy CMA constitutes the main food allergy observed in the pediatric population in Argentina and in many other countries. Soy-based formulas are frequently used as a dairy substitute in pediatric patients with CMA. Our group has found that three soy allergens (A5A4B3, b-conglycinin and P34) cross-react with bovine caseins (BC) and we propose to explore the immunomodulation of CMA using cross-reactive components. Our aim was to design a vaccine based on P34 cross-reactivity CR, to induce oral tolerance in CMA patients. The allergenic properties of the major allergens of soybean (recombinant P34 and P28) were investigated by immunoblotting and basophil activation test using CMA patient sera. Additionally, in vitro recognition of P34 and P28 was evaluated by competitive ELISA using mAb anti alpha-BC and in vivo CR was studied using a cow´s milk mouse model. Finally, we developed an immunotherapy to generate tolerance to cow´s milk proteins CMP by prior sublingual administration of P34 and then orally sensitization with CMP plus choleric toxin. P34 and P28 were both specifically recognized by IgE antibodies of sera from CMA patients. In contrast, only P34 shared epitopes with BC (in competitive ELISA and mouse model), which are responsible for inducing a hypersensitivity reaction in milk allergic mice, thus show its clinical relevance of this cross-reactivity. Pretreatment with P34 reduced clinical manifestations induced by exposure to CMP, presented lower levels of specific-CMP antibodies and (decrease of IgE (p<0,05), IgG1 (p<0,05) compared to untreated), cell-specific CMP responses (IL-5 (p<0,005) and IL-13 (p<0,005) compared to untreated), and negativized skin tests. In conclusion, we can say that sublingual administration of P34 able to induce systemic tolerance, preventing oral sensitization by oral tolerance induction. These results motivate us to continue and increase tolerance induction studies based on cross-reactivity between both systems.