The goal of this project is to find ways to make subunit vaccines work. The approach is to evaluate the adjuvant activities of new chemical entities suggested by the previous work of the investigators. These studies will be coordinated with investigation of the critical properties of effective adjuvants and their mechanisms of action which, in turn, will be used to design even more effective adjuvants. Four new types of chemical entities will be studied: 1) Nonionic block copolymers will be synthesized according to the trend lines of known structure function relationships. 2) Precursors, derivatives and modifications of lipid A will be prepared based on our data that the toxicity of lipid A can be separated from its adjuvant activity and that adjuvant activity may be selective for particular isotypes of immune responses. 3) Lipid conjugated protein carriers which modify the interaction of adjuvants with T cells will be used in conjunction with other adjuvants in an effort to enhance T cell responses and 4) Conjugates of small antigens with Salmonella flagella will be evaluated for immunogenicity. The hapten TNP will be used in initial studies as a model of low molecular weight antigens. Later studies will use peptide antigens of interest to NIAID. Following immunization of mice in standard protocols, immune responses will be assessed in terms of amount, isotype and avidity of antibody by an ELISA, delayed type hypersensitivity, cytotoxic T cells and the induction of suppressor cells. Studies of mechanisms will include immunhistochemistry and autoradiograhy in vivo and antigen presentation and induction of Ia in vitro.
