ABSTRACT
This chapter reviews recent developments in the use of vaccine adjuvants, which function primarily as “vaccine delivery systems.” Hence I will focus on emulsion, liposome, iscom, and microparticle-based adjuvants, whose principal mode of action is the delivery of antigens into the key cells and/or sites that are responsible for the induction of immune responses. Immunological adjuvants were originally described by Ramon [1] as “substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone.” This broad definition encompasses a very wide range of materials [2], including a range of particulate delivery systems. Generally, immunological adjuvants have proven notoriously difficult to classify in any rational way, primarily because their mechanisms of action are often ill defined. Although this chapter will focus primarily on particulate adjuvants, in many situations these have been combined with additional adjuvants. Primarily, adjuvants are components of bacteria and viruses, or synthetic agents that mimic these, and are recognized as “danger signals” by receptors on innate immune cells, including the toll-like receptors (TLRs), which trigger the release of a cascade of proinflammatory cytokines [3]. Hence, many adjuvants have been referred to as representing pathogen-associated molecular patterns (PAMPs), although synthetic molecules can also be used as mimics. A full discussion of both adjuvants and delivery systems is beyond the scope of this chapter, but has been reviewed recently [4]. For an optimal adjuvant effect, it is becoming increasingly common to use delivery systems to target both antigen and adjuvants into the same immunocompetent cells. In these situations, it becomes even more difficult to determine the mechanism of action for the combined adjuvant formulation. In many studies that will be discussed in this chapter, it is clear that synergies between adjuvants and delivery systems are possible and optimal vaccine formulations using a variety of components.
