Role of Adjuvants in Infection and Autoimmunity

Some adjuvants may exert adverse effects upon injection, or on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of their enormous implications for vaccine development. In the search for new and safer adjuvants, several new ones have been developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens results, in part, from the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used in vaccinations today are developed to mimic TLR ligands. Alongside their supportive role in eliciting the immune response to vaccine antigens, however, adjuvants have themselves been found to inflict illnesses of autoimmune nature, defined as "the adjuvant diseases." This chapter looks at the use of silicone as an adjuvant and at connective tissue diseases, as well as the Gulf War Syndrome and Macrophagic myofasciitis following multiple injections of aluminum-based vaccines. There is no question that safer adjuvants are needed for incorporation into future vaccines. In light of new vaccine technologies adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, and cancer and autoimmunity vaccines are also needed. In particular, there is demand for safe and non toxic adjuvants capable of stimulateing cellular (Th1) immunity. Besides alum, many other adjuvants have been approved for use in human vaccines including: MF59 in some viral vaccines; MPL, AS04, As01B, and AS02A against viral and parasitic infections; virosomes for HBV, HPV, and HAV; and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely, in order to circumvent common side effects such as local inflammation and the general malaise caused by the costly whole- body immune response to antigen.