A Vaccine for Schistosomiasis, "SchistoShield"

项目摘要 血吸虫病是一种主要的寄生虫病，可能影响74个国家的10亿人。电流 控制策略主要依靠单独的抗寄生虫药物（吡喹酮），由于 再感染和耐药性的内在威胁。我们已经研制出一种有效的血吸虫病疫苗， 称为SchistoShield®，靶向功能重要的抗原（Sm-p80）， 刺激剂（GLA-SE）。SchistoShield®已在啮齿动物、兔子和狒狒中进行了详尽的测试， 在所有寄生虫生命周期阶段（包括幼虫、蠕虫和产卵、存活）均表现出保护作用， 排泄我们正在完成我们的第二阶段SBIR赠款研究，重点是生产，冻干， 抗原的填充/完成，并将进入三个临床试验（第一个是NIH资助的1期人体试验， 美国，接下来的两项由欧盟资助的1b期试验将在布基纳法索进行 和非洲马达加斯加），从2020年第一季度开始。 为了支持我们即将进行的试验，IIb期赠款将重点用于确保疫苗稳定性所需的研究 按照监管机构的要求，在试验期间提供制剂（DP）。研究将包括 评估长期稳定性、正式运输研究和开发适用于以下方面的灵敏效价测定 后期临床开发。效价测定将包括对小鼠进行免疫接种，然后进行抗体检测 单次注射后的滴度。我们将使用模拟现实生活条件强制降解抗原，并测试 使用我们的效价测定，改变蛋白质以保留免疫功能。我们的目标将是确定 质量参数直接指示效力的损失。 在这些研究结束时，我们将有我们的DP稳定性，正式的运输方法确定，一个敏感的 开发了效价测定，并确定了疫苗效价的关键质量参数。所有这些 研究需要为2期和3期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.