Overview of vaccine adjuvants

Vaccine adjuvants are products or substances coadministered with poorly immunogenic antigens to boost their immune response. Adjuvants such as aluminum salts and Freund's complete and incomplete emulsion adjuvants were some of the early discovered adjuvants about a century ago. Discovery of safe, highly purified, but less immunogenic antigens via innovation in recombinant DNA technology in the early 1980s led to the need for more potent vaccine adjuvants as well as the basis for understanding how adjuvants work. The past few decades of adjuvant research have unraveled mechanisms of adjuvant action resulting in a more focused research on developing of novel adjuvants catering to the desired characteristic immune response. Based on their direct function and interaction with cells, adjuvants can be broadly classified as particulate adjuvants and immune potentiators. Particulate adjuvants help in “delivery” of the antigen to the antigen-presenting cells, whereas immune potentiators broadly work by directly activating the local innate immune system via receptors on antigen-presenting cells to trigger an antigen-specific immune response. Despite the vast history of adjuvant use, very few are approved by the FDA for human use. Increasing knowledge and research on understanding the fundamentals of the desired immune response should facilitate rational development of novel adjuvants. Advancing novel adjuvants requires a careful amalgamation of formulation science, toxicology, and a thorough understanding of immunological aspects. In this chapter, we have reviewed the heritage of vaccine adjuvants, the current status of adjuvant development, and future considerations for developing novel adjuvants.