ABSTRACT
INTRODUCTION Vaccines can be divided into two major families-live, attenuated vaccines and nonreplicating vaccines. Live, attenuated vaccines, such as the measles, rubella, oral polio, and oral typhoid vaccines, consist of a weakened version of the pathogen, which is not pathogenic but immunogenic. The nonreplicating vaccines usually consist of components of the pathogen, isolated chemically or through recombinant DNA technology (e.g., ‘‘subunit vaccines’’ such as the Hepatitis B vaccine). A central component of subunit vaccines are additives called adjuvants, which enhance the magnitude of immune responses. Currently, only alum-an aluminum salt-based substance-is licensed for clinical use in the United States. Live vaccines contain their own ‘‘adjuvants’’—microbial or viral stimuli that activate the immune system. Despite the critical importance of adjuvants in generating robust immune responses, we are largely ignorant of how they work. Clearly, mechanistic insights into how successful vaccines and adjuvants mediate robust and long-lived protective immunity would be of great value in the design of future vaccines against global pandemics and emerging infections. In this context, recent advances in innate immunity research are beginning to provide new insights. It is now clear that many microbial stimuli, including components of vaccines, act via toll-like receptors (TLRs), which therefore represent promising therapeutic targets for the development of novel adjuvants. However, recent evidence suggests that some adjuvants can induce robust adaptive immunity in a TLR-independent manner, perhaps through other receptors in the innate immune system. Therefore, understanding the precise roles played by TLRs and other nonTLRs in the induction and regulation of adaptive immune responses is critical for the design of optimally effective vaccines. In this chapter, we review emerging advances in innate immunity, and how they impact our understanding themode of action of many successful vaccines and adjuvants and guide the design of future vaccines.
