Will adjuvants be needed for vaccines of the future?

Adjuvants improve the uptake of antigens by the immune system, and stimulate antigen-presenting cells (APC) to express "danger signals" such as the secretion of cytokines. The physical changes in antigen distribution can also be brought about by DNA vaccines, which provide persistent antigenic stimulation, access to the endogenous antigen processing pathway and, with the appropriate mode of injection, targeting to APC; however the question of whether DNA vaccines induce danger signals is unresolved. This presentation reviews the particular features of the adjuvant action of Al(OH)3, muramyl dipeptides and saponins, and the danger signals they induce in APC to ascertain whether they provide clues as to how DNA vaccines might be improved. Three conclusions are drawn: (i) adjuvants differ in the relative efficacy with which they stimulate Th1 and Th2 cells; (ii) IL-1 is the only identified common danger signal induced by the three adjuvants; (iii) in the case of both muramyl dipeptides and saponins there are toxic and nontoxic analogues, and the adjuvant activity can be separated from the toxicity. The basis of the difference between the toxic and non-toxic analogues is not clear.