Towards the rational design of Th1 adjuvants

Finding adjuvants in order to enhance immune responses against target immunogens has been a major and recurrent issue for the vaccine industry. It is yet to be solved, most particularly in the context of a growing interest in designing new types of vaccines capable of eliciting Th1 immune responses. A review of synthetic adjuvants which have been (or are being) tested in clinical studies is presented. Importantly, recent advances in our understanding of the physiology of immune responses offer new avenues to design and test candidate adjuvants, based on either synthetic or natural molecules, with the aim to mimic and recapitulate pro-inflammatory signals initiating both innate and adaptative immune effector mechanisms. Thus, adjuvants of the future might be a mixture of molecules selected singularly for a capacity to attract, target or activate professional antigen presenting cells. Used as a combination, such molecules should facilitate antigen presentation by professional APCs and lead to a potent induction of T cell-mediated effector and immune memory mechanisms.