Mechanisms of action of adjuvants

Abstract

Adjuvants are used in many vaccines, but their mechanisms of action are not fully understood. Studies from the past decade on adjuvant mechanisms are slowly revealing the secrets of adjuvant activity. In this review, we have summarized the recent progress in our understanding of the mechanisms of action of adjuvants. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. It appears that adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses. Understanding the mechanisms of action of adjuvants will provide critical information on how innate immunity influences the development of adaptive immunity, help in rational design of vaccines against various diseases, and can inform on adjuvant safety.

Keywords: adjuvants; antigen presentation; cell recruitment and activation; dendritic cells; inflammasomes; innate immunity; mechanisms.

Figure 1

Proposed mechanisms of action of adjuvants. (1) Some adjuvants presumably form a depot at the site of injection, which is associated with slow release of antigen. (2) Other adjuvants are associated with transient secretion of cytokines and chemokines. (3) Secreted cytokines and chemokines are involved in recruitment of various immune cells to the injection site. These recruited cells secrete cytokines and chemokines, in turn attract other immune cells. All these events lead to formation of a local immuno-competent environment at the injection site. (4) The recruited APCs express various PRRs both on the surface (TLRs, CLRs) and intracellularly (NLRs and RLRs), which are recognized and/or are activated by the adjuvants. (5) This leads to maturation and activation of recruited APCs. Mature APCs up-regulate the expression of MHC and co-stimulatory molecules. (6) They are also characterized by increased capacity for antigen processing and presentation. (7) Mature APCs then migrate to the draining lymph nodes to interact with antigen-specific B or T cell to (8) activate potent antibody secreting B cells and/or effector CD8⁺ T cell responses.