Bacterial Polysaccharide Immune Globulin (BPIG) is prepared from donors immunized with H. influenzae b(Hib) pneumococcal and meningococcal vaccines. With previous NIAID support, BPIG has been prepared, characterized, and shown to be efficacious in preventing bacteremic Hib infections in high risk Apache infants. With separate funding from NIAID, a clinical trial to evaluate efficacy against systemic pneumococcal infections is underway and a demonstration project to introduce BPIG into general use to prevent HIB infections in Eskimo infants of the Yukon-Kuskokwim Delta is scheduled to begin in May 1989. The proposed studies are designed to improve further the methods for preparing BPIG, to characterize more precisely the anticapsular antibodies (Abs) in immunized adults and in BPIG, and to develop better standardized assays for Hib, pneumococcal, and meningococcal polysaccharide (Ps) Abs. In order to maximize the Ab response of plasma donors to Ps antigens, we will immunize them with more immunogenic Ps-protein conjugate vaccines and evaluate the quantity and quality of the IgG Ab produced. Alternative and potentially inexpensive methods to enrich Ps Abs will be explored by determining whether affinity chromatography with oligosaccharides can be used to purify Hib Ab from the globulin of unimmunized donors. The pharmacology of BPIG containing higher concentrations of Ab to Hib and to carrier proteins will be examined in high risk groups. Combination passive-active immunization regimens utilizing BPIG and Hib and pneumococcal conjugate vaccines will be examined. Standardized ELISA assays for Ab to Hib, pneumococci and meningococci will be developed and calibrated. The activities of Hib Ps Abs differing in IgG subclass, light chain composition, and G2m(n) allotype will be examined in binding assays, functional assays and in experimental infection. The role of Ab affinity and rheumatoid factors in altering Hib Ps Ab activities in these assays will also be examined. These closely interrelated studies will enhance our basic understanding of the human Ab response to Ps and the functional mechanisms underlying Ab binding to Ps. In addition, they will result in the development of improved methods for immunoprophylaxis of encapsulated bacterial infections in high risk groups. Groups that might benefit from passive immunization include American Indian and Alaskan Eskimo infants, children on cancer chemotherapy with asplenia, sickle cell disease or B cell immunodeficiencies, and secondary contacts of Hib or meningococcal infections.
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