Despite the availability of antibiotics, Hemophilus influenzae b remains a leading cause of morbidity and mortality in children. This study proposes to analyze the idiotypic diversity of human antibodies specific for the major antigen and virulence factor of H. influenzae b, the capsular carbohydrate, polyribosyl-ribitol- phosphate (PRP). Using hybridoma methodology, murine monoclonal antibodies specific from cross-reactive idiotopes of PRP-specific antibodies will be prepared. These anti-idiotopic reagents will be used to determine: the extent to which idiotopes are shared between unrelated humans, whether infants and adults express similar idiotypic repertoires, and whether anti-idiotopic antibodies can prime neonatal rats for protection from H. influenzae b infection. Also, attempts will be made to identify isologous human anti-idiotypic antibodies. These studies will provide insight into the variable region diversity and ontogeny of the human anti-PRP antibody repertoire as well as test the feasibility of using anti-idiotypic antibodies as a protective H. influenzae b vaccine. Identification of human idiotypes and anti- idiotypes is necessary for future studies which seek to determine whether anti-idiotypic antibodies regulate B cell expression in the infant and the adult.
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