β-glucan microparticles targeted to epithelial APN as oral antigen delivery system

Abstract

Enteric diseases still have a devastating impact on global health. Oral vaccination is crucial to prevent intestinal infections, since only vaccines delivered to the intestinal tract elicit potent immune responses at the site of pathogen entry. However, oral vaccines encounter multiple barriers, including poor uptake and tolerance mechanisms, preventing the immune system to react to innocuous environmental antigens. Antigen delivery systems combined with selective targeting seem a promising strategy to overcome these obstacles. The current study evaluates the capacity of aminopeptidase N (APN)-targeted β-glucan microparticles (GPs) as antigen delivery system. Antibodies against APN, an intestinal epithelial receptor, are efficiently oriented conjugated to GPs via the biolinker protein G. The resultant microparticles were analyzed for their antigen load, adjuvanticity and interaction with enterocytes and dendritic cells (DCs). Functionalization of GPs with antibodies neither impedes antigen load nor adjuvanticity. In addition, targeting to APN increases the uptake of microparticles by enterocytes and DCs, leading to an enhanced maturation of the latter as evidenced by an upregulation of maturation markers and a strong pro-inflammatory cytokine response. Finally, oral administration of APN-targeted antigen-loaded particles to piglets elicits higher serum antigen-specific antibody responses as compared to control particles. Taken together, these data support the use of APN-targeted GPs for oral delivery of antigens.