(47f) Mucosal Immunization Utilizing An Engineered Targeting Ligand

Mucosal vaccination is an attractive approach for several reasons. Mimicking the natural route of infection can generate a more complete immune response and delivery can be less invasive. Due to their natural ability to deliver antigens to the lymphatic system, M cells in the mucosa are important sites of antigen uptake. Unfortunately, these cells are extremely rare, occurring in the intestine at a frequency of 1 in 10 billion epithelial cells. One way to overcome this potential limitation is to target M cells using a ligand with high affinity and specificity. We report the development of a vaccine delivery system targeting M cells. We have employed the use of a bacterial surface protein, invasin, present on certain strains evolved to infiltrate the human body via M cells. We have enhanced the affinity of invasin for its primary receptor using protein engineering techniques. The targeting ligand has also been successfully conjugated to the surface of polymeric drug delivery systems encapsulating antigen. This ligand has been shown to remain active by labeling with soluble fluorescent receptor. This system should be capable of protecting antigen during transit though the gastric intestinal tract, target M cells, and activate antigen presenting cells. Together this protein based vaccine system should provide complete protection against desired pathogens.