THE ROLE OF ADJUVANTS IN RETROVIRAL VACCINES

The global HIV epidemic continues unchecked. Reports to the World Heal th Organization's Global Programme on AIDS indicate that more than 14 million persons have become infected with HIV and more than two millio n have died with AIDS. The spread of AIDS has generated a worldwide ma ndate for the development of safe and effective vaccines against HIV. Vaccines have been the most effective defense against other viral dise ases such as polio and smallpox. However, the development of a vaccine against HIV-1 is a formidable task due to the variation of the virus, inadequate animal models of HIV disease, and the lack of correlates o f protective immunity. Several candidate HIV vaccines are composed of synthetic, recombinant, or highly purified subunit antigens. Vaccines composed of subunit antigens generally are considered to be safer than traditional whole-killed or live-attenuated vaccines. However, purifi ed subunit vaccines often are inherently less immunogenic than traditi onal vaccines. Immunologic adjuvants are agents that act generally to enhance specific immune responses to vaccine antigens. Formulation of experimental HIV vaccines with potent immunologic adjuvants is an attr active approach for amplifying and directing immune responses to highl y purified antigens. Alum adjuvants, consisting of aluminum salts, fir st described in the 1920s, remain the only adjuvants in U.S.-licensed vaccine formulations. Novel adjuvants now undergoing preclinical and c linical testing with experimental subunit Vaccines include detoxified lipid A, adjuvant emulsions, liposomes, biodegradable microspheres, mu ramyl peptides, and saponins. Adjuvants have been shown to elicit cyto toxic T-cell responses as well as antibody to subunit antigens. Some o f these adjuvants also have been shown to lower the threshold levels o f antigen necessary to evoke immune responses. This review will descri be several types of immunological adjuvants now being evaluated in exp erimental retroviral vaccines and mechanisms of their adjuvanticity, I nitial steps being taken toward the standardization of adjuvant safety testing will also be discussed.