A Novel Adjuvant-based Probiotic Platform for Generating Tolerance Therapeutics

Autoimmune and allergic diseases affect overof the world population and are continuing to riseOur goal is to develop a novel adjuvant based probiotic platform to rapidly create tolerance inducing therapeutics for the treatment of allergy and autoimmune diseaseFor thiswe will leverage the reovirus protein sigmapwhich is a powerful tolerance adjuvantFusion proteins consisting of pwith an antigen of choice bind to mucosal M cells in the intestinal tract and generate a tolerogenic immune response to that antigenThe tolerance response is driven by the induction of suppressive regulatory T cellsregulatory B cellsand an increase in anti inflammatory cytokinesTo reduce the complexity and cost associated with producing recombinant pbased proteinsand to improve delivery of oral biologicsour strategy is to deliver pbased immune modulators in the context of LlactisTo validate our approachwe will create a Llactis strain expressing a pfusion protein connected to three serodominant house dust miteHDMallergensWe will then demonstrate that oral administration of this Llactis strain prevents allergic symptoms in a HDM mouse modelCompletion of this proposal will establish a novel adjuvant based probiotic platform for rapid development of tolerance therapeutics