A Vaccine for Schistosomiasis, "SchistoShield"

项目总结 血吸虫病是一种主要的寄生虫病，可能会影响74个国家的10亿人。当前 控制策略主要依靠单独的抗寄生虫药(吡喹酮)，事实证明这是不够的，因为 既有再感染，又有耐药性的固有威胁。我们已经开发出一种有效的血吸虫病疫苗， 名为SchistoShield®，靶向一种具有重要功能的抗原(Sm-p80)，该抗原具有强大的免疫- 刺激物(GLA-SE)。SchistoShield®已在啮齿动物、兔子和狒狒身上进行了详尽的测试，并已 在寄生生命周期的所有阶段，包括幼虫、蠕虫和产卵、存活和 排泄物。我们正在完成我们的第二阶段SBIR赠款研究，重点是制造、冷冻干燥和 抗原的填充/完成，将进入三个临床试验(第一个由美国国立卫生研究院资助的第一阶段人体试验 美国，以及欧盟资助的下两个1b阶段试验，将在布基纳法索进行 非洲的马达加斯加)将于2020年第一季度开始实施。 为了支持我们即将进行的试验，这项第二阶段的拨款将集中在确保疫苗稳定性所需的研究上。 根据监管机构的要求，在试验期间提供药品(DP)。该研究将包括 评估长期稳定性，正式的运输研究，以及适用于 后期临床发展。效力测试将包括免疫小鼠，然后是抗体 一次注射后的效价。我们将使用模拟现实生活条件强制降解我们的抗原，并测试 通过我们的效价分析，改变蛋白质以保持免疫功能。我们的目标将是确定哪些 质量参数直接表明效力的丧失。 在这些研究结束时，我们将有关于稳定性的DP，确定正式的运输方法，一个敏感的 制定了效力分析，并确定了疫苗效力的关键质量参数。所有这些都是 需要进行研究，为第二阶段和第三阶段临床试验以及未来的许可和部署做准备。

PROJECT SUMMARY Schistosomiasis is a major parasitic disease which could impact up to a billion people in 74 countries. Current control strategies rely primarily on anti-parasitic drugs alone (praziquantel) which has proven inadequate due to both reinfection and the inherent threat of drug resistance. We have developed a potent schistosomiasis vaccine, termed SchistoShield®, targeting a functionally important antigen (Sm-p80) formulated with a potent immune- stimulator (GLA-SE). SchistoShield® has been exhaustively tested in rodents, rabbits, and baboons and has exhibited protection at all parasitic life-cycle stages including larvae, worms, and egg laying, survival, and excretion. We are completing our Phase II SBIR grant research focused on manufacture, lyophilization, and fill/finish of the antigen and will be entering into three clinical trials (first an NIH funded Phase 1 human trial in the USA, and next two Phase 1b trials funded by the European union which will be performed in Burkina Faso and Madagascar in Africa) beginning in the first quarter of 2020. To support our upcoming trials, this Phase IIb grant will focus on studies required to ensure stability of the vaccine drug product (DP) for the duration of the trials as required by regulatory agencies. The research will include assessing long-term stability, formal shipping studies, and development of a sensitive potency assay suitable for later stage clinical development. The potency assay will include immunization into mice followed by antibody titers after a single injection. We will forcibly degrade our antigen using simulated real-life conditions and test the altered protein for retention of immunological function using our potency assay. The goal will be to identify which quality parameters are directly indicative of a loss of potency. At the end of these studies we will have our DP on stability, formal shipping methods identified, a sensitive potency assay developed, and have identified critical quality parameters of potency of the vaccine. All these studies are required in preparation for Phase 2 and 3 clinical trials and future licensure and deployment.