Examining the Effects of Immulina to Increase Immune Resilience against Influenza Virus Infections

项目2：摘要/总结 拟议中的密西西比大学（UM）植物膳食补充剂研究中心（BDSRC）是 专注于填补与基于螺旋藻的产品ImmulinaTM的潜力相关的知识空白， 促进对流感和其他呼吸道病毒感染的抵御能力和/或恢复能力。 在2017 - 18报告年度，仅在美国，流感就导致959，000名患者住院， 79,400人死亡。 UM BDSRC将由一个管理核心，一个植物核心和两个研究项目组成。 项目2，ImmulinaTM口服补充剂对宿主抵抗流感病毒感染的评价，将在 由Gailen马歇尔，医学博士，博士，教授和密西西比临床研究的执行主任指导 和UM医疗中心的试验中心。与他密切合作的将是Khalid Ashfaq，博士，DVM，DTVM。 项目2旨在包括利用小鼠模型（1 - 2年）和基于生物标志物的研究。 人类模型（3 - 5年级），旨在确定ImmulinaTM补充剂对增加宿主 抵御流感病毒感染的致病作用。它将调查以下问题 假设：ImmulinaTM以其最佳口服形式给予将改变宿主的抗病毒免疫反应，表现为 通过增加NK细胞数量和/或活性、抗流感H和N抗体滴度以及CD8+细胞毒性T细胞 淋巴细胞（CTL）对流感感染的细胞。 为了研究我们的假设，我们将实现以下具体目标： 1.在三种非致死性小鼠模型中评估ImmulinaTM口服给药对流感的抵抗力 病毒感染（预防、前驱症状和恢复），以确定ImmulinaTM的最有效效用 增强宿主免疫力，提高抗病毒能力; 2.证实Braun型脂蛋白激活TLR2信号通路是导致 ImmulinaTM增强宿主抗病毒感染免疫力的机制; 3.在人体模型中确定ImmulinaTM补充剂的最佳形式和剂量， 最大化增加NK细胞数量和/或活性的效果，增加支持细胞因子（IL-15，IL-16，IL-17，IL-18）， 2，IGNg）、流感特异性抗体滴度和CTL数; 4.根据两种初始变化，建立最佳NK、细胞因子、抗体和CTL应答的时间轴 和最大的变化和变化的持续时间，一旦ImmulinaTM停止在正常和 免疫受损（老年）人类研究参与者;以及 5.检查在ImmulinaTM使用之前、期间或之后给予常规流感疫苗的效果， 研究接受ImmulinaTM补充剂与 安慰剂

PROJECT 2: ABSTRACT/SUMMARY The proposed University of Mississippi (UM) Botanical Dietary Supplements Research Center (BDSRC) is focused on filling in knowledge gaps related to the potential for the Spirulina-based product, ImmulinaTM, to promote resilience against and/or recovery from influenza and, by extension, other respiratory viral infections. During the 2017-18 reporting year in the U.S. alone, influenza resulted in 959,000 patient hospitalizations and 79,400 deaths. The UM BDSRC will be composed of an Administration Core, a Botanical Core, and two research projects. Project 2, Evaluation of ImmulinaTM Oral Supplement for Host Resistance to Influenza Virus Infection, will be directed by Gailen Marshall, MD, PhD, Professor and Executive Director of the Mississippi Clinical Research and Trials Center at UM Medical Center. Working closely with him will be Khalid Ashfaq, PhD, DVM, DTVM. Project 2 is designed to include studies utilizing both mouse models (Years 1-2) and biomarker-based human models (Years 3-5) aimed at establishing the impact of ImmulinaTM supplementation on increasing host resilience against the pathogenic effects of influenza virus infection. It will investigate the following hypothesis: ImmulinaTM given in its optimal oral form will alter the host antiviral immune response, manifested by increases in NK cell numbers and/or activity, anti-flu H and N antibody titers, and CD8+ cytotoxic T lymphocytes (CTL) against flu-infected cells. To investigate our hypothesis, we will achieve the following specific aims: 1. Evaluate oral administration of ImmulinaTM in three non-lethal mouse models of resilience against influenza A virus infection (prophylaxis, prodrome and recovery) to determine the most effective utility of ImmulinaTM for enhancing host immunity to improve antiviral resilience; 2. Confirm that activation of the TLR2 signaling pathway by Braun-type lipoproteins is a primary causal mechanism through which ImmulinaTM enhances host immunity against antiviral infection; 3. Determine the optimal form and dosage of the ImmulinaTM-based supplement in the human model that will maximize effects on increasing NK cell numbers and/or activity, increased supporting cytokines (IL-15, IL- 2, IGNg), influenza-specific antibody titers and CTL numbers; 4. Establish the timeline for optimal NK, cytokine, antibody and CTL responses in terms of both initial changes and maximal changes and duration of the change once the ImmulinaTM is discontinued in normal and immune compromised (elderly) human research participants; and 5. Examine the effects of routine influenzas vaccine given before, during, or after ImmulinaTM use to investigate influenza antigen-specific immune responses in individuals receiving ImmulinaTM supplement vs placebo.