Recent advances in the development of novel mucosal adjuvants and antigen delivery systems.

Mucosal infections and associated diseases remain a major socio-economic burden to society. Since parenteral immunizations fail to induce efficient protective immunity at mucosal surfaces, mucosal immunization is a logical approach to prevent and treat mucosally-initiated infections. All currently approved human mucosal vaccines are based on attenuated or killed whole pathogen cells but this strategy does pose safety concerns. Therefore, substantial effort is being invested to develop safe and effective mucosal adjuvants and delivery systems for mucosal vaccines. Encouragingly, some of these have progressed to advanced preclinical and clinical studies. This review discusses the promising preclinical research and the potential applications of several novel mucosal adjuvants and delivery systems: an archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, 3',5'-cyclic diguanylic acid (c-di-GMP) and detoxified bacterial AB(5) toxins. The potential and challenges in targeting M cells for mucosal vaccination are also discussed.