Unravelling Immune Enhancement by Immulina

揭秘 Immulina 的免疫增强作用

• 批准号: 9916572
• 负责人: Chalet Tan
• 金额: $ 32.46万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9916572
• 关键词: Acute; Agonist; Antigens; Binding; Biological; Biological Assay; Biological Markers; Blood Circulation; CD8-Positive T-Lymphocytes; Cells; Data; Dendritic Cells; Development; Disease; Dose; Drug Delivery Systems; Effector Cell; Extracellular Space; Food; Formulation; Gel; Generations; Health; Homeostasis; Host Defense; Human; Immune; Immune response; Immunity; Immunologics; Immunology; In Vitro; Influenza; Interleukin 2 Receptor Gamma; Interleukin-15; Interleukin-2; Knowledge; Lipoproteins; Liquid substance; Lung; Lymphoid; Mediating; Mississippi; Molecular; Morbidity - disease rate; Mus; Natural Immunity; Natural Killer Cells; Natural Products; Peyer' s Patches; Pharmacodynamics; Pharmacology; Phase; Play; Population; Process; Production; Proteins; Respiratory System; Role; Scientist; Signal Transduction; Site; Small Intestines; Spirulina preparation; Standardization; T memory cell; TLR2 gene; Toll-like receptors; Universities; Virus; Virus Diseases; Virus Replication; Weight; Work; Zoonoses; adaptive immune response; adaptive immunity; capsule; cytokine; draining lymph node; experience; improved; in vivo; influenzavirus; intestinal epithelium; liquid formulation; macrophage; migration; monocyte; mortality; mouse toll-like receptor 2; oral supplementation; pandemic disease; protective effect; receptor; resilience; respiratory infection virus

PROJECT SUMMARY Influenza is an acute respiratory virus infection that poses endemic, zoonotic and pandemic threats to human health with significant morbidity and mortality. Natural killer (NK) cells and virus-specific CD8 T cells are key effector cells in launching effective immune responses against influenza virus infection. ImmulinaTM, a high molecule-weight fraction of Spirulina extract, contains Braun-type lipoproteins that trigger Toll-like receptor 2 (TLR2)-mediated NFκB activation in human monocytes and mouse macrophages. Our recent preliminary data show that daily treatment of a liquid formulation of Immulina caused notable expansion of circulating NK population in mice. Building upon our substantial experience in drug delivery, pharmacodynamics and immunology, we propose to develop an optimized liquid formulation of Immulina, evaluate its protective effect against influenza virus infection, and elucidate the mechanism of action in vitro and in vivo. The specific aims of the proposal are: (1) develop an optimized liquid formulation for Immulina; (2) evaluate the pharmacodynamics of Immulina and identify in vivo biomarker(s); (3) investigate the molecular mechanism on the immune enhancement by Immulina. The successful completion of this project will result in the development of an improved formulation of Immulina and the identification of in vivo biomarkers for Immulina treatment.

项目摘要 流感是一种急性呼吸道病毒感染，对人类构成地方性、人畜共患和大流行威胁。 人类健康，发病率和死亡率很高。自然杀伤（NK）细胞和病毒特异性CD 8 T细胞是 在启动针对流感病毒感染的有效免疫应答中的关键效应细胞。ImmulinaTM，一个高 螺旋藻提取物的分子重量分数，含有触发Toll样受体2的Braun型脂蛋白 人单核细胞和小鼠巨噬细胞中（TLR 2）介导的NFκB活化。我们最近的初步数据 表明Immulina液体制剂每日处理引起循环NK的显著扩增 在小鼠中的种群。基于我们在药物输送、药效学和 免疫学，我们建议开发一种优化的Immulina液体制剂，评价其保护作用 抗流感病毒感染，并阐明体外和体内的作用机制。具体目标 的建议是：（1）开发一个优化的液体配方Immulina;（2）评估 研究Immulina的药效学并鉴定体内生物标志物;（3）研究Immulina的分子机制。 Immulina的免疫增强作用该项目的成功完成将导致发展 Immulina的改进制剂和Immulina治疗的体内生物标志物的鉴定。