The proposed studies will further elucidate the mechanisms by which group B streptococci (GBS) interact with host defense components which mediate their opsonization and clearance.
The aim of these studies is to prove the hypothesis that physiologic maturation of one or more immune mechanisms during the first months of life provides an explanation for the age-specific interval of infant susceptibility to invasive GBS infection. The binding of human plasma fibronectin (FN) to GBS and relevance of the maturation of plasma FN levels to opsonic efficiency for GBS in infancy will be defined by: (1) employing radiolabeled FN chromatographically purified to determine the strain and serotype specificity of FN binding to GBS; (2) exploring the role of proteins, sialic or lipotechoic acid as receptors for FN binding and the influence of purified opsonins (Clq and specific antibody) in modulating binding; and (3) correlating plasma FN levels with maturation of opsonic efficiency for GBS in relationship to the maturation of complement and specific antibody in the first six months of life. These studies will employ opsonically defined sera from normal infants and a group surviving GBS disease. The reticuloendothelial system (RES) clearance of GBS will be characterized using a neonatal guinea pig (GP) model of infection by (1) determining the efficiency of bloodstream clearance and RES localization (hepatic and splenic) by GBS serotype in normal and C4-deficient GP; (2) defining the roles of terminal sialic acid residues and the sufficiency of the alternative complement pathway (ACP) in modulating RES clearance; and (3) blocking selectively hepatic asialoglycoprotein or phagocytic Fc receptors to determine the mechanism by which RES clearance occurs in neonates. Finally, the evolution of immunospecific IgG subclass antibodies to Ia and III-GBS will be determined between birth and six months of age by ELISA to establish their relationship to invasive disease vs. colonization and their influence on the development of functional activity.
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