ABSTRACT
INTRODUCTION The past decade has seen dramatic progress in our understanding of immune mechanisms and host defense. Along with the ability that vertebrates have to acquire immunity to pathogenic antigens by expanding specific populations of T and B cells and making cytokines and antibodies, scientists have discovered that like invertebrates, we have multiple innate pathways to activate more generic host responses through a whole new family of receptors. Over 80 years ago, Ramon demonstrated that it was possible to artificially increase antigen-specific levels of diphtheria or tetanus antitoxin by the addition of bread crumbs, agar, tapioca, starch oil, lecithin, or saponin to the vaccines (1). Since then, aluminum salts have been the dominant substance used and are still the only adjuvant currently used in licensed vaccines in the United States. The field has become much more sophisticated recently with the introduction of numerous new adjuvants and new concepts regarding the mechanisms of action. In this brief chapter, we review the modern adjuvants used in a variety of current and experimental human vaccines. After a more general discussion of adjuvants, including their definition, mechanisms of action, and safety, we will discuss recent clinical trials of investigational adjuvants. For additional study of this complex subject, including a historical perspective, the reader is referred to published reviews of vaccine adjuvants (see Refs. 2-4).
