A Vaccine for Lymphatic Filariasis, LFGuard™

淋巴丝虫病疫苗 LFGuard™

• 批准号: 10408790
• 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 2023-12-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408790
• 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; Persons; 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.

项目摘要 淋巴丝虫病（LF）是一种蚊子传播，被忽视的热带疾病（NTD），影响超过1.2亿 居住在72个国家 /地区的人们。 LF感染的当前控制策略，该策略依赖于年度大众药物 对“处于危险”人群的管理（MDA）未能部分中断疾病传播 LF目前尚无许可的预防性疫苗，其中包括在 最近20年已经超越了啮齿动物测试。这部分是由于保护性不佳，但也是由于 鉴于其真正被忽视的性质，缺乏推进技术的资源。 我们已经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™。该疫苗由制定的蛋白质抗原BM-Haxt组成 带有TLR4激动剂GLA-ON-ALUM。配制后，我们的疫苗高度稳定，几乎无菌 啮齿动物的免疫力（> 95％）和非人类隐私的明显保护（70％）。迄今LFGuard™有 经过广泛的测试并确认其在不同动物模型中的预防潜力和安全性 作为小鼠（n = 980），蒙古的沙鼠（jirds）（n = 220）和恒河猕猴（n = 60）。除了治疗LF， LFGuard™还显示了狗作为心脏虫的疫苗的巨大希望。 SBIR 2阶段的建议将使我们能够将LFGuard™转移到包括GMP在内的临床前开发中 制造，瓶和稳定性和效率测试。临床研究和支持毒理学研究将是 设计和稳定性将通过短期和长期稳定计划确认。最后，我们会的 在执行毒理学研究之前，与FDA进行预先会议。当这些研究是 完整，这种重要的抗原将被中毒，以进入有史以来第一次淋巴的第一个人类临床试验 丝虫病疫苗。我们提出了以下SBIR第2阶段赠款的目标：（1）BMHAXT的制造 CGMP（2）进行临床前的指定研究。