IMMUNE RESPONSE TO S PNEUMONIAE CAPSULAR POLYSACCHARIDE

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DESCRIPTION (Adapted from applicant's abstract): Streptococcus pneumoniae with capsular polysaccharide (PS) especially those with 6A and 6B serotype capsule, are significant human pathogens and often antibiotic resistant. Vaccines against S. pneumoniae are being developed using capsular PS, which can elicit protective antibodies (AB) against infection with elicit Ab to 6A capsular PS in humans. Current vaccines as well as the conjugate vaccines under development contain only serotype 6B PS. They have found that 10 to 25 percent of vaccines may produce Ab which poorly opsonize S. pneumoniae 6A serotype. Furthermore, by inducing immune memory for ineffective Ab these vaccines may alter one's subsequent immune response to S. pneumoniae 6A ( original antigenic sin ). They have also found that anti-6A Ab are often derived from two V lambda 2 family genes, products of which express 8.12 idiotype, a marker for nephritogenic Ab to dsDNA. Pneumococcal infections may prime B cells for production of anti dsDNA Ab. Specific aims of their study are to: A) Study clinical relevance of Ab poorly opsonizing S. pneumoniae 6A serotype, by determining their in vivo protective activity and frequency of individuals with poorly opsonic (to 6A) Ab among infant and elderly vaccines. B) Study pneumococcal vaccination for potential induction of immune memory for Ab poorly opsonizing S. pneumoniae 6A serotype, including the impact on immune memory development (antigenic sin) in SCID mice. C) Study pneumococcal vaccination for potential priming of B cells which later produce anti dsDNA Ab. A key assumption in formulating S. pneumoniae vaccines is that cross reactive Ab are functional. So far, the function of cross reactive Ab has not been critically examined. If their study finds that 6B PS often induces Ab with little protective function against S. pneumoniae 6A, then the vaccine formulation may need to be modified. PS protein conjugate vaccines are promising approaches for immunizing children against many PS antigens from bacterial pathogens. Yet their immunobiology is still poorly understood. The investigator's long term research goal is to study immunobiology of PS and PS protein conjugate vaccines.