Development of a Univalent Vaccine Against Group B Streptococci Infection

描述(由申请人提供)：B组链球菌(GBS)已成为新生儿发病率和死亡率以及与妊娠相关的发病率的最重要的感染原因之一。孕妇感染GBS使母亲和孩子面临并发症的高风险。在怀孕期间，GBS可导致尿路感染、绒毛膜羊膜炎、产后伤口感染、肾盂肾炎、败血症，很少发生脑膜炎。虽然与GBS相关的妊娠发病率很少危及生命，但新生儿感染可能是严重和致命的。绒毛膜羊膜炎可能导致自然流产或死产。疾病控制和预防中心目前的建议包括在妊娠晚期对所有妇女进行GBS筛查，并在分娩期间对GBS阳性妇女进行抗生素预防。最近的研究表明，多达24%的孕妇接受预防性抗生素治疗GBS。显然，GBS是一种非常普遍的感染，在健康成年人的生殖器和胃肠道定居。根除GBS在怀孕人口中的殖民的努力没有成功。1985年，美国国家科学院指出，GBS疫苗是一个重要的目标，因为“针对孕妇的主动免疫计划将最有希望控制早发和晚发疾病。”根据这一目标，并由于抗生素预防GBS感染的局限性和风险，我们已着手开发母体GBS疫苗。我们建议将GBS表面蛋白C5a肽酶包裹在一种可生物降解的聚合物中，作为一种新型疫苗，它将诱导黏膜和系统免疫，能够消除母体定植并赋予后代保护性免疫。我们的初步数据支持了我们方法的有效性。为了了解建立免疫记忆的细胞和分子机制，我们选择了应该促进短期和长期免疫反应的体外和体内模型。我们的方法将基于生物可降解聚合物的新型佐剂的开发与分子研究相结合，以阐明抗原负载佐剂刺激免疫反应的机制。这种综合方法对于解决合理设计有效刺激免疫系统的疫苗递送系统这一挑战至关重要。总之，我们的目标是设计一种安全的单价疫苗，消除母亲的任何GBS血清型感染，并保护孩子免受GBS疾病的感染。公共卫生相关性：该项目旨在通过使用疫苗根除孕妇及其后代中的B组链球菌感染。我们的目标是开发一种安全有效的疫苗，促进短期和长期的免疫反应。这样的疫苗将防止过度使用抗生素，并防止可能对母婴造成严重甚至致命的并发症。

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.