A Vaccine for Lymphatic Filariasis, LFGuard™

项目总结 淋巴丝虫病(LF)是一种通过蚊子传播的被忽视的热带疾病(NTD)，影响超过1.2亿人 生活在72个国家的人们。依赖年度集体用药的LF感染控制策略 对高危人群的管理(MDA)未能阻断疾病的传播，部分原因是慢性 再感染。目前还没有获得许可的预防性疫苗可供LF使用，并且在 在过去的20年里，啮齿动物测试已经取得了进步。这部分是因为保护不力，但也是因为 鉴于其真正被忽视的性质，缺乏推动这项技术的资源。 我们开发并建立了第一个成功的多价重组融合蛋白(BM-HAXT)，用于 LF的预防称为LFGuard™。这种疫苗是由一种蛋白质抗原BM-HAXT组成的 使用TLR4激动剂GLA-on-Alum。在配制疫苗时，我们的疫苗高度稳定，几乎无菌 啮齿类动物的免疫力(95%)和非人灵长类动物的显著保护(70%)。迄今为止，LFGuard™已经 在不同的动物模型上进行了广泛的预防潜力和安全性的测试和确认 作为小鼠(n=980)、蒙古沙鼠(n=220)和恒河猴(n=60)。除治疗LF外， LFGuard™在狗身上也显示出作为心虫疫苗的重大前景。 这份SBIR第二阶段提案将允许我们将LFGuard™转移到临床前开发中，包括GMP 制造、装瓶、稳定性和药效测试。一项临床研究和一项辅助毒理学研究将 设计，稳定性将通过短期和长期稳定计划得到确认。最后，我们会 在执行毒理学研究之前，与FDA召开IND前会议。当这些研究是 完成后，这种重要的抗原将进入有史以来第一次淋巴系统的人类临床试验。 丝虫病疫苗。我们为SBIR第二阶段赠款提出了以下目标：(1)在以下条件下制造BmHAXT CGMP(2)进行临床前IND使能研究。

PROJECT SUMMARY Lymphatic filariasis (LF) is a mosquito-transmitted, neglected tropical disease (NTD) affecting over 120 million people living in 72 countries. Current control strategies for LF infection which rely on annual mass drug administration (MDA) to the “at-risk” populations has failed to interrupt disease transmission partly due to chronic reinfection. There is no licensed prophylactic vaccine currently available for the LF, and of those tested over the last 2 decades have advanced beyond rodent testing. This is partly because of poor protection, but also due to lack of resources to advance the technology given its truly neglected nature. We have developed and established the first successful multivalent recombinant fusion protein (Bm-HAXT) for the prophylaxis of LF called LFGuard™. This vaccine is comprised of a protein antigen, Bm-HAXT, formulated with the TLR4 agonist GLA-on-Alum. When formulated, our vaccine is highly stable and provides nearly sterile immunity in rodents (>95%) and significant protection in non-human primates (70%). To date LFGuard™ has been extensively tested and confirmed for its prophylactic potential and safety in different animal models such as mice (n=980), Mongolian gerbils (jirds) (n=220), and rhesus macaques (n=60). In addition to treatment of LF, LFGuard™ has also shown significant promise in dogs as a vaccine for heartworms. This SBIR Phase 2 proposal will allow us to move LFGuard™ into pre-clinical development including GMP manufacture, vialing, and stability and efficacy testing. A clinical study and a supporting toxicology study will be designed, and stability will be confirmed through both short- and long-term stability programs. Finally, we will conduct a pre-IND meeting with the FDA prior to execution of the toxicology study. When these studies are complete, this important antigen will be poised to enter the first human clinical trials for the first ever lymphatic filariasis vaccine. We propose the following aims for this SBIR Phase 2 grant: (1) Manufacture of BmHAXT under cGMPs (2) Perform pre-clinical IND-enabling studies.