An FcRn-mediated exosome-based oral vaccine enhanced co-mucosal immunity via targeting intestinal epithelial transport and lymphatic activation

MSN@ME induces immune responses across gastrointestinal, respiratory, and reproductive mucosae. • FcRn mediates intestinal transport of intact OVA/MSN@ME to the lamina propria and lymphatic system. • MSN@ME enhances gut antigen uptake, dendritic cell maturation, and lymphatic targeting. It is imperative to adopt immune strategies that provide effective protection at the mucosal entry points of pathogens. Direct mucosal vaccination can effectively induce local mucosal immune responses and activate systemic mucosal immunity. However, the low uptake of antigens by antigen-presenting cells due to the mucus layer and epithelial barriers limits the effectiveness of vaccines. The neonatal Fc receptor (FcRn), known as a “mucosal gateway,” is thought to enhance drug uptake in intestinal epithelial cells. The study found that milk-derived exosomes (ME) can effectively utilize a “hitchhiking” strategy by encapsulating subunit antigens (such as ovalbumin, OVA) combined with immunostimulatory mesoporous silica nanoparticles (MSN) to create an oral vaccine that efficiently traverses the intestinal epithelial barrier and reaches the mucosal lamina propria. Our findings demonstrate that OVA/MSN@ME effectively maintains the oral stability of antigens and facilitates their translocation to the lamina propria, preliminarily suggesting an FcRn-mediated transport mechanism. This process subsequently triggers robust immune responses within gut-associated lymphoid tissues. These results indicate that the MSN@ME composite system is a promising delivery strategy for targeting mucosal epithelial cells, offering a potent means to enhance mucosal immunity against infectious diseases. Download: Download high-res image (169KB) Download: Download full-size image