The objective of this renewal program is to further explore the natural history of infections caused by Streptococcus pneumoniae, group B streptococcus (GBS), and Hemophilus influenzae type b. These three pathogens account for most serious bacterial infection in infants and children and remain significant causes of disease in otherwise healthy young women (GBS puerpural infections) and in aging adults (the pneumococcus). They share many biological and immunological features, and their disease potential has continued to be high, despite advances in antibiotic therapy and development of vaccines. Satisfactory modes of prevention have yet to be realized. This program will focus upon key aspects of host- parasite relationships that may help explain the development of disease and suggest new approaches to its prevention The Core Project provides clinical support for the entire program. While continuing to yield important epidemiologic information through new and ongoing clinical studies, it provides essential patient materials, bacterial isolates, and epidemiological data from well defined patient populations. Seroepidmeiological investigations Project 1 will make use of these materials to more precisely define "protection" in immunological terms. Its studies will evaluate functional (opsonophagocytic) antibody with respect to measured properties, critically examining the roles of avidity and blocking by specific IgA antibodies. Studies of antibody functions other than opsonization will focus upon the activation of platelets and neutrophils in vitro and in acute disease. The immunochemistry of GBS polysaccharides will be studied in Project 2. The similarities between GBS antigens and glycoconjugates of the human host will be examined in relation to colonization and disease. The molecular basis for these similarities will be studied with modern NMR techniques, monoclonal antibodies, and chemically modified GBS antigens: The concept of "virulence" will be examined with respect to biological properties of the bacteria and their polysaccharide capsules. Project 3 will study the surface protein antigens of the pneumococci to develop a protein typing system and to evaluate the possible application of surface proteins as candidate vaccines. The epidemiology of surface protein--will be studied in correlation with the human antibody response to pneumococcal colonization and disease.