A Vaccine for Lymphatic Filariasis, LFGuard™

淋巴丝虫病疫苗 LFGuard™

• 批准号: 10200657
• 负责人: DARRICK Albert CARTER
• 金额: $ 100万
• 依托单位: PAI LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200657
• 关键词: Adjuvant; Affect; Agonist; Animal Model; Antigens; Biological; Biological Assay; Brugia malayi; Canis familiaris; Cells; Chronic; Clinical; Clinical Research; Clinical Trials; Contracts; Country; Coupled; Culicidae; Development; Disease; Engineering; Fermentation; Filaria bancrofti; Filarial Elephantiases; Future; Grant; Helminths; Human; Immunity; Individual; Infection; Infection Control; Interruption; Lead; Lymphatic; Lymphedema; Macaca mulatta; Mus; Nature; Parasites; Pathology; Pharmaceutical Preparations; Pharmacotherapy; Phase; Populations at Risk; Preventative vaccination; Preventive vaccine; Procedures; Process; Production; Prophylactic treatment; Proteins; Recombinant Fusion Proteins; Records; Research; Resources; Risk; Rodent; Rodent Model; Running; Safety; Seeds; Small Business Innovation Research Grant; Sterility; TLR4 gene; Technology; Testing; Time; Toxicology; Vaccination; Vaccines; Vial device; Work; Writing; aluminum sulfate; design; disability-adjusted life years; disease transmission; efficacy testing; gerbil/jird; global health; in vivo; meetings; neglect; neglected tropical diseases; nonhuman primate; physically handicapped; pre-clinical; preclinical development; programs; prophylactic; stability testing; transmission process; vaccine candidate

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.

项目概要 淋巴丝虫病 (LF) 是一种由蚊子传播、被忽视的热带疾病 (NTD)，影响超过 1.2 亿人 居住在 72 个国家的人们。目前LF感染的控制策略依赖于每年的大规模药物 对“高危”人群的管理（MDA）未能阻止疾病传播，部分原因是慢性病 再次感染。目前还没有获得许可的 LF 预防疫苗，并且在过去的测试中 过去 20 年的进步已经超越了啮齿动物测试。造成这种情况的部分原因是保护措施不力，但也有一些原因 鉴于其真正被忽视的性质，缺乏资源来推进该技术。 我们开发并建立了第一个成功的多价重组融合蛋白（Bm-HAXT） LF 的预防称为 LFGuard™。该疫苗由蛋白质抗原 Bm-HAXT 组成，配方为 与 TLR4 激动剂 GLA-on-Alum 一起使用。配制后，我们的疫苗高度稳定，几乎无菌 啮齿类动物的免疫力（>95%）和非人类灵长类动物的显着保护（70%）。迄今为止，LFGuard™ 已 在不同的动物模型中对其预防潜力和安全性进行了广泛的测试和证实，例如 例如小鼠 (n=980)、蒙古沙鼠 (n=220) 和恒河猴 (n=60)。除了治疗 LF 外， LFGuard™ 在狗身上也显示出了作为心丝虫疫苗的巨大前景。 该 SBIR 第 2 阶段提案将使我们能够将 LFGuard™ 转入临床前开发，包括 GMP 制造、装瓶以及稳定性和功效测试。将进行临床研究和支持性毒理学研究 设计，稳定性将通过短期和长期稳定性计划来确认。最后，我们将 在执行毒理学研究之前，与 FDA 召开 IND 前会议。当这些研究 完成后，这种重要的抗原将准备进入第一个淋巴管的首次人体临床试验 丝虫病疫苗。我们为 SBIR 第 2 阶段拨款提出以下目标：(1) 根据 BmHAXT 制造 cGMP (2) 进行临床前 IND 支持研究。