Development of oral vaccines to stimulate mucosal and systemic immunity: barriers and novel strategies.

Many questions regarding the induction of mucosal and humoral immunity through oral vaccination exist. Efficacy is dependent on the physicochemical properties of the antigen, the gastrointestinal environment, the presence of adjuvants, and the mode of delivery. Understanding how these factors interrelate will be critical to the development of new oral vaccines. A number of approaches are currently being studied to enhance the immune response. These include chemical conjugation, immunization with recombinant bacteria and viruses, and mucosal adjuvants. Vaccine delivery systems prepared from natural or synthetic polymers is a particularly promising area because many of the current methods to induce mucosal stimulation can be incorporated within these systems. Thus, the polymeric delivery system functions as a platform to facilitate uptake by M-cells and prolong antigen presentation and stimulation of the Peyer's patches. This Review examines some of the physiological and immunological barriers associated with oral vaccination and discusses novel strategies to overcome such barriers.