New horizons in adjuvants for vaccine development.

Adjuvant molecules, particularly toll like receptor (TLR) agonists have been in development for decades, though until now only a natural TLR 4 ligand (mono-phosphoryl lipid A, MPL) has been incorporated into licensed vaccine products, in formulations than enhance and complement the MPL activity. The inclusion of MPL-based formulations into vaccines has been based on enhancing antibody responses to subunit antigens, and has provided important proof-of-concept for enhancing desired immune responses to defined molecular targets. Challenges remain in adjuvant development, particularly for those that stimulated effective T cell responses for both preventative and therapeutic vaccines. The discovery of molecules, many based on RNA, that stimulate innate and adaptive immune responses and have the ability to stimulate potent CD8 T cell responses, has opened the door for development of a new generation of vaccines.