Antigen delivery systems and immunostimulation

The immune system evolved to free the host from invading noxious pathogens. Vaccines are inoculated as a prophylactic measure in order to program the immune system for accelerated recognition and elimination of specific pathogens. During vaccination the immune system is exposed to attenuated or inactivated microorganisms, or their fragments. The immune response to these structures, in contrast to virulent pathogens, is often inadequate for the generation of memory cells or immune effector elements such as antibodies, perforines, granzymes or cytokines. Vaccine adjuvants help to overcome these limited responses. They provide instructive signals for the host immune system by mimicking the conditions associated with virulent infection. Hence, they either enhance and prolong expression of antigen components to reactive T cells in lymph nodes (signal 1) or they increase expression of membrane-bound or soluble costimulatory molecules (signal 2). The enhancement of both signals by vaccine adjuvants is not mutually exclusive. Moreover, adjuvants may encode a third signal instructing the type of immune reaction to be generated. Supported by animations this presentation addresses putative immunological concepts of vaccine adjuvant activity, a phenomenon long been known as "the immunologist's dirty little secret". Insight in the mechanisms that underlie adjuvant-induced immunostimulation and generation of memory cells will facilitate rational vaccine design.