UC Davis

Polysaccharide A, a commensal molecule produced by the gut-symbiont Bacteroides fragilis, has shown tremendous potency in ameliorating inflammatory diseases in various mouse models by eliciting tolerogenic T cell activity. The tolerance-inducing capacity in combination with its polymeric structure makes PSA an intriguing biomaterial for the formulation of tolerogenic nanoparticles. We hypothesize that the encapsulation of allergen within PSA nanoparticles (NPs) will show significant improvements in efficacy and safety over traditional allergen-only oral immunotherapies due to PSA NP’s ability to (i) induce Treg differentiation and deliver allergen simultaneously, and (ii) to shield the allergen from IgE receptor-mediated mast cell activation until internalization by intestinal dendritic cells. We show that PSA NPs can be readily fabricated using water/oil emulsification with chemical crosslinking and maintain immunoregulatory capability, including TLR2 stimulation and tolerogenic dendritic cell differentiation. Furthermore, in-vitro assays indicate that PSA NPs can effectively deliver encapsulated antigen to dendritic cells and mediate antigen-specific T regulatory cell proliferation. In addition, oral gavage of PSA nanoparticles show promising trends in ameliorating allergic symptoms in two mouse models of food allergy. PSA NPs have the potential to become a “plug-in-play” system to induce specific tolerance to any encapsulated antigen.