Vaccine Adjuvants' Mode of Action : Unraveling "the Immunologist's Dirty Little Secret"

Most modern vaccines, based only on well-defined purified antigens, are usually insufficient for proper immune induction in the absence of co-administrated immunostimulatory components called adjuvants (adjuvare (Latin) to help). Vaccine adjuvants come in many forms, which are not unified by a common structure. The choice of a suitable adjuvant for a certain vaccine antigen formulation is often difficult due to the fact that little is known about the mechanisms underlying adjuvant activity in general. As a result, the local and systemic reactions of the antigen-adjuvant combination have to be determined by trial and error. Because of this uncertainty adjuvants have been called "the immunologist's dirty little secret" (Janeway, 1989). Ideally, future vaccines contain adjuvants with predictable activity. During the last decades we have learned in more detail how adaptive immune responses in a normal individual evolve. A number of immunological theories may explain the critical mechanisms underlying adjuvanticity, each of them championing either distinct pathways or distinct key steps within immunological pathways. Here, the most important concepts are discussed in relation to the most recent knowledge in vaccine adjuvant activity