Adjuvants are substances that enhance immune responses, that is, they stimulate an immune response of greater magnitude than that which occurs when the antigen is given alone. Most protein antigens are poor immunogens when given mucosally and may induce immunological tolerance instead. Thus, mucosal adjuvants are needed to overcome this potential outcome of mucosal antigen exposure. Because different mucosal surfaces have different microenvironments, mucosal adjuvants have different effects at different mucosal sites. The most effective adjuvants used in vaccines are derived from bacterial components. These agents are recognized as ligands for toll-like receptors (TLRs) that serve to detect pathogen-associated molecular patterns (PAMPs) and activate innate immune cells. An unusual feature of the lipopolysaccharide (LPS) adjuvanticity is that it can be delivered at a different site and at a different time than antigen. LPS activates the immune system by binding to TLR4, resulting in stimulation of macrophages to produce cytokines such as IL-1 and colony stimulating factors (CSFs), stimulation of B cell proliferation, alteration of MHC class II expression on antigen-presenting cells (APCs), and stimulation of IFN-. production and of delayed-type hypersensitivity (DTH). © 2005 Elsevier Inc. All rights reserved.
