Beta-glucan particles as novel antigen delivery systems: towards oral vaccination

Gastro-intestinal infections are still a main cause of enteric diseases and mortality among humans and animals. Oral vaccination is crucial in generating an adequate local mucosal immune response, however the hostile environment of the intestinal tract and oral tolerance remain huge obstacles that inhibit the ability to successfully develop new mucosal vaccines. A promising strategy for vaccination with safe, biodegradable non-replicating antigen delivery systems has gained increased interest for eliciting cellular and humoral immune responses. The current study evaluates the potential of β-glucan (BGP) and calcium carbonate (CaCO3)- and mannitol-templated polyelectrolyte particles as mucosal antigen delivery systems and their adjuvant characteristics. All microparticle types are efficiently internalized by Caco-2 and HT-29 cell lines and in particular the BGP triggered the expression of pro-inflammatory cytokines IL-23p19, IL-8 and beta-glucan receptors in activated Caco-2 cells and CCL20 in HT-29 cells. In contrast, the expression level of TGF-b, an important mediator of the active component of oral tolerance, was significantly downregulated in HT-29 cells. Oral administration of BGP induced intestinal adaptive immune responses characterized by an increased sIgA and secretory component production. Interestingly, adoptive transfer experiments pointed out the proliferation of naïve OVA-specific CD4+ OT-II cells and increased IL-17 production in spleens of BGP-fed mice upon antigen restimulation. These results demonstrate that BGP enhances MHC-II-presentation and promotes mucosal immune responses preferably skewed towards an Th17 response and represents a promising strategy for oral vaccination