Bert Devriendt
Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University
Enteric diseases remain a global health issue. Enteropathogens, such as rotavirus and enterotoxigenic E. coli (ETEC), are one of the leading causes of diarrhoea in children. Moreover, these enteropathogens also infect livestock species, including piglets, resulting in economic losses due to growth retardation, increased drug use and elevated mortality. To control enteric infections, oral vaccination holds great promise, since vaccines delivered to the intestinal tract can elicit protective immunity at the site of pathogen entry. Moreover, oral vaccination has additional advantages, such as decreased production costs and relative ease of administration without the risk of needle-stick injuries. However, despite many efforts, the development of oral vaccines remains cumbersome. A significant hurdle to successful vaccine design is our poor understanding of host-pathogen interactions at the intestinal epithelium and how these affect intestinal immunity. In addition, oral vaccines face many challenges, including the hostile environment of the gut, oral tolerance and the poor uptake by the epithelial barrier. To surmount these hurdles novel antigen delivery systems in combination with selective targeting to the intestinal epithelium are developed. Here we evaluated yeast ghosts as oral vaccine delivery system in piglets. Yeast ghosts are mainly composed of cell wall beta-glucans, which are known for their immune-enhancing properties upon recognition by the main beta-glucan receptors dectin-1 and complement receptor 3. A variety of antigens can be efficiently loaded in these microparticles without degradation and without disrupting the immune-enhancing capacity of the yeast ghosts. To enhance their uptake by the intestinal epithelium, antigen-loaded yeast ghosts were functionalized on their surface with monoclonal antibodies targeting the apical intestinal epithelial receptor aminopeptidase N (APN). This selective targeting to APN enhanced the uptake of the yeast ghosts by enterocytes and dendritic cells. In addition, they triggered the activation of these dendritic cells and elicited antigen-specific immunity upon oral vaccination in piglets. Taken together, these data support the use of APN-targeted yeast ghosts for oral delivery of vaccine antigens and motivate further in vivo research of these promising antigen carriers.