Infection with Streptococcus pneumoniae remains a major cause of morbidity in the young, the elderly and those with compromised immunity. Despite antibiotics, morality from pneumococcal bacteria has never declined below 30%, and in recent years, there has been an increase in antibiotic resistant organisms among clinical isolates. An accumulation of data suggests that antibodies protect an organism from pneumococcal infection, and prior to the advent of the antibiotic era immune serum constituted an effective anti-pneumococcal therapy. For these reasons, they propose to develop immunologically based approaches to pneumococcal therapy. They propose to identify antibodies that can be used in passive therapy. They will generate these from combinatorial phage libraries derived form spleen cells of pneumovax immunized individuals. They propose to simulate somatic mutation in vitro using libraries of human anti-pneumococcal antibodies that are protective in mice against clinically significant stains to generate the most effective antibodies for the largest number of clinically important stereotypes. They will then use these antibodies to obtain peptide mimotopes which bind anti-polysaccharide antibodies and stimulate production of protective anti-pneumococcal antibodies. Finally, they will explore the use of various vectors that might be used to administer such peptide mimotopes. These include an attenuated strain of shigella and adenovirus.
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