The purpose of this investigation will be to delineate the opsonins mediating neonatal immunity to group B streptococcal (GBS) infections which protect the majority of exposed infants from developing invasive infection and which restrict the age-specific susceptibility to these infections to the first three months of life. The evolution of type-specific antibody concentrations (radioactive antigen-binding assay) and the maturation of classical and alternative complement pathway components (radial immunodiffusion and hemolytic assays) will be quantitated and correlated with maturation of functional bactericidal activity in vitro by means of an opsonophagocytic assay. Sera from a group of infants passively acquiring moderate to high (greater than 2 Mug/ml) or low (less than 2 Mug/ml) concentrations of specific antibody to type Ia or type III GBS will be assessed at-monthly intervals from birth to six months of age. Potential differences in a group of infants recovering from invasive GBS disease will be assessed in the same manner. To evaluate the possibility that maturational deficiency in one or more IgG subclass proteins might enhance the propensity of some infants exposed to GBS to develop invasive infection, patterns of IgG subclass protein evolution will be compared longitudinally for a group of normal infants colonized with type Ia or III, GBS and a group developing invasive GBS infection. Finally, type Ia and type III-specific GBS antibody will be purified employing antigen-coated latex beads to determine the IgG subclass specificity of immunoglobulin produced in response to natural infection, and to determine the functionally active portion of the molecule, as well as the concentration required to initiate bactercidal activity. The delineation of opsonins which mediate protection from invasive infection for the majority of infants and which define the age-restricted nature of GBS infections is prerequisite for planning efficacious means of prevention of GBS infections. Precise definition of the opsonic requirements for efficient bactericidal activity against GBS will enable judicious use of therapeutic adjuncts such as fresh frozen plasma and intravenous immunoglobulin to ameliorate the severity of these infections in young infants.
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