IMMUNOLOGICAL ADJUVANTS FOR MODERN VACCINE FORMULATIONS

Many of today's candidate vaccines are composed of synthetic, recombinant, or highly purified subunit antigens. Vaccines composed of these purified subunits generally are considered to be safer than traditional whole-killed or live-attenuated vaccines. Often, however, purified subunit vaccines are inherently less immunogenic. Immunologic adjuvants are agents that act to generally enhance specific immune responses to vaccine antigens. Formulating experimental vaccines with potent immunologic adjuvants is an attractive approach for amplifying and directing immune responses to highly purified antigens incorporated into combination vaccines containing one or more of these immunogens. Alum adjuvants, consisting of aluminum salts, first described in the 1920s, remain the only adjuvants in United States licensed vaccine formulations. Novel adjuvants now undergoing preclinical and clinical testing with experimental subunit vaccines include detoxified lipid A, adjuvant emulsions, liposomes, biodegradable microspheres, muramyl peptides, and saponins. Such adjuvants have been shown to elicit cytotoxic T-cell responses as well as antibody to subunit antigens. Some of these adjuvants also have been shown to lower the threshold levels of antigen necessary to evoke immune responses. Reducing the needed dose of antigens through the use of novel adjuvants should facilitate the design of multivalent and combination vaccines that incorporate multiple antigens. In this paper I describe several types of immunologic adjuvants now being evaluated in experimental retroviral vaccines. I also discuss the mechanisms of adjuvanticity and the standardization of adjuvant safety testing.