The morbidity and mortality associated with neonatal group B streptococcal (GBS) infections have remained significant despite their consistent sensitivity to the penicillins. Although several lines of evidence suggest that antibody to type-specific GBS plays a critical role in protection against disease, an effective measure for the prevention and therapy of neonatal GBS disease has yet to be established. We have recently developed an infant rat model for GBS disease. This model has obvious similarities to human GBS infection (e.g., colonization and subsequent development of systemic disease, age dependency, high mortality) and thus provides the unique opportunity to study the prophylactic and therapeutic values of various immunoglobulins and penicillin.
The specific aims are as follows: (1) To refine and improve the infant rat model of type III GBS gastrointestinal colonization and systemic disease (bacteremia and meningitis). (2) To evaluate the effect of GBS sepsis on the rates of disappearance of passively administered total IgG and homologous (type III GBS) and heterologous (H. influenzae type b) IgG antibody following intraperitoneal administration of immune serum globulin (ISG) in infected and uninfected newborn rats. (3) To evaluate the therapeutic efficacy of human IgG and mouse hybridoma antibodies (IgG, IgM and IgA) in conjunction with penicillin in reducing mortality and enhancing bacterial clearance from blood and CSF. (4) To assess the prophylactic value of systemic and oral immunoglobulin (ISG, hybridoma antibodies) against type III GBS colonization of the gastrointestinal tract and systemic disease. (5) To examine the prophylactic efficacy of penicillin G against type III GBS colonization and systemic disease in the newborn rats. The information derived from this proposal should enhance our understanding of passive immunization which is applicable to other bacterial infections.
