Vaccine adjuvant technology: from theoretical mechanisms to practical approaches.

Poorly immunogenic antigens depend on vaccine adjuvants to evoke an immune response. In addition, adjuvants largely determine the magnitude, quality, time of onset and the duration of immune responses to co-administered antigens. As late as 1989, Janeway aptly called adjuvants: "the immunologist's dirty little secret". This statement reflected the ignorance on the mechanisms of action of most known adjuvants. Yet, rational vaccine design involves a logical choice of adjuvant based on a knowledge of their mode of action and their effects on product efficacy and safety. However, even today the key processes critical for immune induction in general and those evoked by vaccine adjuvants in particular are being disputed among immunologists. This paper presents the four most important concepts likely to explain some of the mechanisms of vaccine adjuvants. They include: (i) the geographical concept of immune reactivity; (ii) the depot concept; (iii) the hypothesis of pathogen-structure recognition, and (iv) the damage/endogenous danger theory. These paradigms are based on observations gathered in mammalian species, largely in murine models. In aquatic animals the processes underlying immune induction will at least partly overlap those in mammals. However, due to inherent species differences, certain pathways may be different. Rational vaccine design, a difficult goal in mammals, is further hampered in aquatic animals by the lack of immunological tools in these species. Extensive trial and error-based approaches have yielded adjuvant candidates for various fish species, with acceptable safety and proven efficacy, some of which are presented.