The perfect mix: recent progress in adjuvant research

Key Points New vaccines are often less immunogenic than previous vaccines, and adjuvants are therefore required to assist in the induction of potent and persistent immune responses, to reduce the amount of antigen and limit the number of injections. Some new vaccines also need adjuvants that are capable of inducing potent cell-mediated immunity in addition to an antibody response, such as T helper (T H ) 1 responses and cytotoxic T lymphocyte (CTL) responses. Recent advances in basic immunology have demonstrated the crucial role of some innate immune signals in modulating — both quantitatively and qualitatively — the subsequent adaptive response. Among these, some agonists of Toll-like receptors (TLRs) would in theory constitute promising adjuvants. Vaccine research can take advantage of these discoveries to design and develop more focused and efficient adjuvants, such as new synthetic agonists of TLRs. Moreover, new formulations can combine different immunostimulants, including TLR agonists and non-TLR 'classical' adjuvants. These compounds can act in synergy, and targeting them towards antigen-presenting cells could further increase and focus their action. In parallel, new biochemical and immunological tools and assays have been developed to characterize and evaluate these new adjuvants, both in vitro and in vivo . The combination of information obtained in several assays, for example in animal models and human primary or transformed cells, can provide more accurate information on the potency and safety of these new adjuvants before use on humans. Vaccine research scientists can now chose between a larger panel of compounds and technologies to design and develop the formulation that would drive the most efficient and safest response with respect to each considered pathogen, keeping in mind that each antigen–adjuvant couple is unique. In addition to improving our understanding of target antigens for vaccines and their correlates of protection, recent advances in immunological research, particularly in our understanding of innate immunity, have also had a major impact on adjuvant research. Bruno Guy reviews the practical applications of our increased understanding of the immune system in the design and development of more specific and focused adjuvants. Developing efficient and safe adjuvants for use in human vaccines remains both a challenge and a necessity. Past approaches have been largely empirical and generally used a single type of adjuvant, such as