Development of a Univalent Vaccine Against Group B Streptococci Infection

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DESCRIPTION (provided by applicant): Group B Streptococci (GBS) has emerged as one of the most important infectious causes of neonatal morbidity and mortality and pregnancy-related morbidity. A GBS infection in the pregnant patient places the mother and child at high risk for complications. In pregnancy, GBS can cause urinary tract infections, chorioamnionitis, postpartum wound infection, pyelonephritis, sepsis, and rarely meningitis. While GBS-related morbidity in pregnancy is rarely life- threatening, neonatal infection can be severe and fatal. Chorioamnionitis may lead to spontaneous abortion or stillbirth. Current recommendations from the Centers for Disease Control and Prevention include screening all women during the third trimester for GBS and giving antibiotic prophylaxis during labor to GBS positive women. Recent studies demonstrate that up to 24% of pregnant women receive antibiotics prophylactically for GBS. Clearly, GBS is a very prevalent infection which colonizes the genital and gastrointestinal tract of healthy adults. Attempts to eradicate colonization of GBS in the pregnant population have been unsuccessful. In 1985, the National Academy of Sciences indicated that a GBS vaccine is an important goal because "a program of active immunization aimed at pregnant women would have the best prospects of controlling early-onset and late-onset disease." In accordance with this goal, and because of the limitations and risks associated with antibiotic prophylaxis for GBS infection, we have undertaken the development of a maternal GBS vaccine. We propose to encapsulate a GBS surface protein, C5a peptidase, within a biodegradable polymer as a novel vaccine that will induce both mucosal and systemic immunity capable of eliminating maternal colonization and conferring protective immunity to offspring. Our preliminary data supports the effectiveness of our approach. In order to understand the cellular and molecular mechanisms that establish immunologic memory, we have chosen both in vitro and in vivo models that should promote both short and long-term immune responses. Our approach combines the development of novel adjuvants based on biodegradable polymers with molecular studies to elucidate mechanisms by which antigen-loaded adjuvants stimulate immune responses. Such an integrated approach is essential in solving the challenge of rationally designing vaccine delivery systems that effectively stimulate the immune system. In summary, it is our goal to design a safe, univalent vaccine that would eliminate any serotype GBS infection in the mother and protect the child from acquiring GBS disease. PUBLIC HEALTH RELEVANCE: This project is aimed at eradicating Group B Streptococci infections in pregnant women and their offspring through the use of a vaccine. Our goal is to develop a safe and effective vaccine that will promote a short and long-term immune response. Such a vaccine would prevent the over use of antibiotics and prevent possible serious or even fatal complications to the mother and child.