Recombinant Probiotics for Allergen Immunotherapy

Research efforts to improve the efficacy of Allergen Immunotherapy (AIT) involve the discovery of new adjuvant. Some strains of probiotic bacteria are able to induce up-regulation of co-stimulatory molecules in DCs, promote TH1 cytokine production and trigger Treg differentiation and activity. In mouse models, they have been shown to prevent or suppress the harmful TH2 response and to potentiate allergen- or allergoid-based immunotherapy of type I allergic diseases. These observations could explain the effectiveness of the prolonged administration of probiotics in the prevention of allergic disorders in infants. Consequently, the probiotics could be used as adjuvant for AIT. However, the simultaneous administration of probiotics and AIT might not come to specific responses because of degradation and not optimal presentation to APC. Moreover, the lack of specificity of the immunological response might be overcome by using probiotic bacteria expressing the sensitizing allergen. This would allow the stimulation of the intestinal immune system by both immunomodulating factors at the same site. Only a few studies noticed the development of AIT strategies based on recombinant bacteria expressing the allergen. However, most of them reported basic favorable immunomodulatory properties, rather than showing the development of immune tolerance or symptoms reduction. The allergen sequestration inside the bacterial cell may represent limits for these preventive and therapeutic approaches. Recently, our research group developed a novel AIT strategy based on a food-grade bacterium Streptococcus thermophilus (ST) with TH1 skewing property, able to produce the allergen intracellularly and to release it at the gut-associated lymphoid tissue (GALT) level thanks to its intrinsic autolytic behavior with tolerance induction, and readdressing the pre-existing allergen-elicited TH2 response. Hence, the present knowledge on the subject will be critically considered in this review, underlying the most recent experimental achievements.