Adjuvants in perspective.

Many vaccines currently under development and testing are composed of synthetic, recombinant, or highly purified subunit antigens. Vaccines composed of these subunit antigens are often considered to be safer than whole-inactivated or live-attenuated vaccines. However, vaccines containing purified subunit antigens are often less immunogenic than traditional vaccines. Immunological adjuvants are agents that enhance specific immune responses to vaccines. Formulation of vaccines with potent adjuvants is an attractive approach for enhancing immune responses to subunit antigens. Adjuvants have diverse mechanisms of action and should be selected for use based on the route of administration and the type of immune response (antibody, cell-mediated, or mucosal) desired for a particular vaccine. Adjuvant mechanisms of action include: (i) increasing the biological or immunological half-life of vaccine antigens; (ii) improving antigen delivery and presentation; and (iii) inducing the production of immunomodulatory cytokines. Through modulation of cytokine responses, adjuvant formulations can be designed that favour the development of Th1 (type 1) or Th2 (type 2) immune responses to vaccine antigens. Novel adjuvants are currently undergoing preclinical and clinical testing with experimental vaccines, including vaccines against HIV-1. Standardized preclinical adjuvant safety tests are also being developed.