The aim of the proposed research is to test the feasibility of enhancing the immune response of viral antigens by microencapsulation in slow release biopolymers. Because the immunogenicity of poliovirus viral antigens has been extensively characterized, the poliovirus subunit antigens provide an excellent model system with which to test the ability of controlled release devices to enhance the immunogenicity of these antigens. Specifically, a combination of chemical, biochemical and immunological approaches are proposed to study the effectiveness of microencapsulated poliovirus antigens to induce antibody responses and the feasibility of using biocompatable polymers to control release and presentation of viral antigens during immunization and potentially increase the induction of neutralizing antibodies. To achieve these goals: 1. Individual poliovirus antigens will be encapsulated into several different hypdrophobic degradable and non- degradable (FDA approved) polymers. The antigen- imbedded polymers will be characterized physically and the release profiles determined in vitro and in mice. 2. The antibody response induced in mice by the microencapsulated poliovirus antigens will be characterized. The immune response induced by the microencapsulated antigens will be characterized and compared with response induced by antigen-Freunds adjuvant emulsions or with antigen-alum adjuvant mixtures. 3. The molecular mechanisms of the phenomenon of """"""""wetting"""""""" will be studied. Methods will be sought to overcome this often encountered problem with controlled release of biologically active proteins. 4. The ability of the microencapsulated antigens to elicit and stimulate T cell responses will be examined. This response will be compared to that induced by the intact virion. Successful vaccines must be able to induce a immune response which is sufficient to protect the host from the adverse consequences of viral infection. The experiments described here are designed to contribute to the development of methods and techniques that potentially will increase the general utility of viral and subviral antigens as successful vaccine antigens.
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