Microencapsulation of vaccine provides the advantages of controlled and targeted release for the enhancement of the immune response. For the majority of the pathogens listed in this RFA, the respiratory and gastrointestinal tracts represent the site of infection on portal of entry. Both influenze virus and Streptococcus pneumoniae primarily exert their pathophysiologic effects through acute, localized infections of the respiratory epithelium. The antibodies present in the mucus which bathes the nasopharynx and bronchial tree are predominated by secretory IgA which is locally produced by plasma cells within the pulmonary lamina propria. In contrast, the normally sterile bronchial and alveoli predominantly contain IgG antibodies which are passively derived from the intravascular pool. Although sIgA antibodies are effective in virus neutralization, the prevention of bacterial adherence to epithelia, and are correlated with resistance to influenza challenge, parenteral immunization is not effective at inducing sIgA antibody production. However, our preliminary studies show that oral immunization stimulates antibody production not only in the gut, but serum, saliva and bronchial- alveolar wash (BAW) fluids. In addition, we have found that oral administration of microcapsules to mice results in their rapid and selective uptake by the Peyer's patches. We will investigate the effectiveness or oral, as compared to systemic, immunization with microencapsulated and nonencapsulated pneumococcal and influenza virus vaccines in order to determine the ability of targeted delivery and controlled release to potentiate the systemic and pulmonary mucosal immune responses. RIAs will be used to quantitate the vaccine-specific antibodies of the IgM, IgG and IgA isotypes in the serum, saliva and gut and BAW fluids. PCA will be employed to determine the potential for these immunization methods to potentiate immediate hypersensitivity. The relative efficacy of these various immunization methods to confer protection against pulmonary disease will be evaluated in aerosol challenge studies with viable pneumococci and influenza virus.
