The majority of viral vaccines establish a state of systemic protective immunity by injection of live attenuated or inactivated virus preparations. The use of injectable vaccines has reduced the incidence of many viral diseases. Nevertheless, their usage is associated with some undesirable side effects. Live attenuated virus vaccines can cause systemic complications; inactivated vaccines can have local reactogenicity and even induce an allergic state. An alternative to the use of injectable vaccines is the mucosal administration of non-replicating antigens. A major focus of the Virus Research Institute is the study of delivery vehicles. Microencapsulation is the core technology in this endeavor. The SBIR Phase I work goal is to develop microsphere configured vaccine vehicles based on the we water soluble polyphosphazenes. This goal will be accomplished by optimizing size and composition of microspheres and determining the dose and mucosal route of administration that maximize the rapidity, amplitude and duration of the antibody response to a single antigen dose. The distribution of the antibody response over the Ig isotypes, as well as over the IgG subclasses and the cellular immune response will be determined. Finally, the protective efficacy of the polymer microsphere immunization regimen in an animal model will be evaluated.