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on immune cells, and different adjutants have very divergent effects on the same cells. Waksman (1979) made the point that one must define the target cell affected by the adjuvant and the cellular and molecular modes of action of the adjuvant on the target cell. This information is either rudimentary or nonexistent for most adjuvants. Recently, more highly purified molecules have been isolated from traditional adjuvants, such as muramyl dipeptide from mycobacteria and monophosphoryl lipid A from endotoxin. This may simplify the dissection of their effects.

Although many if not all of these mechanisms are likely to apply to mucosal adjuvants as well, there is little information on agents with mucosal adjuvanticity, despite a great need for such agents. Mucosal immunization is the route of choice for protection from many pathogens, but the development of effective mucosal vaccines has lagged, in part due to a lack of suitable mucosal adjuvants. Most protein antigens are not only poor immunogens when given mucosally but also induce tolerance instead of immunity. Mucosal adjuvants are needed to overcome this potential outcome of mucosal antigen exposure. Cholera toxin has been shown to enhance the immunogenicity of relatively poor mucosal immunogens when it is mixed or conjugated together and given orally; thus, cholera toxin and its B subunit have generated a great deal of interest as potential adjuvants for vaccines.

Scientific Rationale for Vaccines against Autoimmune Diseases

During this past century, the number of diseases attributable to the body’s own self-reactivity has risen, so that now it is recognized that there are autoimmune diseases directed against every organ, as well as systemic diseases affecting a broad range of systems. Examples of these diseases include diabetes, rheumatoid arthritis, multiple sclerosis, thyroiditis, myocarditis, and systemic lupus erythematosus.

Within the last 15 years, the subfield of autoimmunotherapy within immunology has made impressive strides, along with the detailed knowledge of the initiation and propagation of autoimmune diseases. Nevertheless, almost to the present, the major treatments have been (1) generic anti-inflammatory agents such as steroids, which have well-known, serious side effects; or (2) cytostatic and cytotoxic drugs whose nonspecific effects on unrelated systems lead to additional morbidity and mortality. In model animal systems, a wide variety of specific therapies in combination with the above general agents have been explored successfully with the aim of transferring this technology to human use.

Several general approaches have been attempted in the effort to either prevent or to alter the course of autoimmune diseases. One strategy is to employ specific antigens or peptides for the induction of immune tolerance among the relevant cells. This approach requires that the antigen or peptide can be defined, although more recently it has been clear that bystander regulation induced by a specific agent could be successful in preventing initiation of other immunospeci-

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