The major focus of this renewal application is to continue studies of the major defined cell surface localized protein antigen of group B streptococci, specifically the c (formerly Ibc, (composed of trypsin-resistant (TR) and trypsin-sensitive (TS) components) and R proteins of group B streptococci (GBS). This will involve further purification of the components of the c protein, as well as the IgA binding protein that has been identified, and to assess the role of antibodies to these protein as host defense mechanisms against infection with strains possessing the protein antigenic markers. The contribution of these proteins antigentic markers of GBS serotypes to the virulence of the organism and pathogenesis of disease is suggested by in vitro and in vivo findings. The interaction of strains bearing the protein antigens with phagocytic cells and antibody will be pursued by a number of integrated approaches to further our understanding of host responses to these GBS constituents. These surface localized protein antigens may account for variation in the biological behavior of GBS and strain- to-strain variation. The specific research goals are: (1) to pursue further purification and characterization of the c protein, including the IgA binding protein; (2) to study characteristics of IgA binding in GBS strains of major serotypes bearing the c proteins; (3) to pursue the in vitro and in vivo biological activity of polyclonal rabbit antisera to the TR and TS proteins; (4) to characterize further the IgG1 monoclonal antibodies that we have produced to the TR and TS proteins; (5) to produce additional mouse monoclonal antibodies against the TR and TS proteins; (6) to study the presence of antibodies against the TR and TS antigens in the sera of mothers and newborn infants and other adults infected or colonized with group B streptococci; (7) to study the immunogenicity of the TR and TS antigens and their capacity to confer immunological protection by immunization; (8) to study mechanisms of resistance to killing of strains bearing the TR and TS antigens; (9) to pursue studies on the role of R proteins and their role in immunity to GBS. Future projection of these studies includes consideration of these proteins as immunogens that may enhance the immunogenicity of GBS polysaccharide type antigens and thereby be included in vaccine development. In addition, since antibodies against these proteins may confer protection directly, they could contribute to preventive and therapeutic strategies for GBS disease in infants.
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