The successful elimination of pathogens following prophylactic immunization depends to a large extent on the ability of the host’s immune system to recognize when it is necessary to become activated and how to respond most effectively, preferably with minimal injury to healthy tissue. In the design of effective, nonreplicating vaccines, immunological adjuvants serve as critical components—other than the antigens—which instruct and control the selective induction of the appropriate type of antigen-specific immune response. Although vaccine adjuvants are recognized as a group of most powerful immunomodulatory agents, little is known about the mechanisms underlying their activity.

This article discusses both well-known and very recent paradigms of immune induction that are likely to explain vaccine adjuvant activity at the cellular and molecular level. As key immunological events it addresses the influence of adjuvants on the delivery of vaccine antigens to particular lymphoid tissues over time, as well as adjuvants’ influence on the activation status of antigen-presenting cells (APCs). In addition, this article attempts to categorize the known types of immunological adjuvants according to these concepts. Future investigations addressing these paradigms may enlighten the secrets of immune induction and prove helpful in the rational design of vaccines.