Targeting Yeast Ghosts to Epithelial CD13 Promotes Mucosal Immunity

Most pathogens invade the host at mucosal surfaces. Protecting against gut-dwelling pathogens requires intestinal immunity induced by oral vaccination, however the road towards efficient oral immunisation remains challenging. Selective targeting of antigens and their encapsulation into microparticles have been envisaged to tackle the main hurdles associated with oral vaccination, i.e. the poor uptake of vaccine antigens, their degradation by the harsh gastrointestinal (GI) environment as well as the tolerogenic microenvironment permeating the GI tract. Recently, our group explored targeting absorptive enterocytes, which vastly outnumber M cells, to promote antigen uptake by the GI tract. Here, we demonstrate that antibody-mediated targeting to the epithelial, endocytotic receptor CD13 on porcine and human small intestinal enterocytes facilitates antigen uptake by these cells and results in an enhanced mucosal immunity. We further expand these findings by combining targeting to CD13 and microencapsulation of antigens through surface decoration of antigen-loaded yeast ghosts with CD13-specific antibodies. Yeast ghosts are comprised of a β-glucan shell and have an inherent mucosal adjuvanticity. CD13 targeting led to an enhanced uptake of these yeast ghosts by enterocytes and dendritic cells and boosted the functional maturation of the latter. This novel combinatorial approach is anticipated to accelerate oral vaccine development.