Artificial Ecology Sink as prophylaxis against viral infection

人工生态水槽预防病毒感染

• 批准号: 9348755
• 负责人: Zhilei Chen
• 金额: $ 222.75万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9348755
• 关键词: Antibodies; Area; Caring; Cells; Chikungunya virus; Culicidae; Dengue Virus; Ecology; Extinction (Psychology); Focal Infection; Foundations; Frequencies; Generations; Goals; HIV; Habitats; Health; Human; Human Resources; Immune; Immune system; Infusion procedures; Intravenous infusion procedures; Organ Transplantation; Organism; Patients; Population; Population Growth; Pregnancy Trimesters; Prophylactic treatment; Protein Engineering; Proteins; Saliva; Source; T-Lymphocyte; Vaccines; Viral; Virus Diseases; Woman; Zika Virus; base; gene therapy; immunological status; pandemic disease; pathogen; public health relevance; theories; vaccine development

Abstract The overall goal of the project is to create a protein-based viral prophylaxis (PVP) that will provide short-term (~2-3 months) protection against various viral infection following each intravenous infusion. This PVP approach is inspired by the ecological source-sink theory which states that the population of an organism in a landscape is controlled by the frequency of habitats that either support (source) or do not support (sink) its population growth. A population will decline towards extinction when the fraction of sink habitats in a landscape exceeds a threshold frequency. According to this source-sink theory, the spread of viral infection in the body, from a limited local infection (e.g. cells directly contacting the saliva of an infected mosquito), is largely contributed by the below the threshold amount of sink cells (sink habitats) in the body (landscape). The central hypothesis of the project is that the introduction of viral ‘sink’ cells in the body can act as prophylaxis against the viral infection. In this project, I proposed to convert host cells into artificial viral sinks by functionalizing them with PVP. The duration of protection (2-3 months), although much shorter than that of a vaccine, will confer adequate protection in many scenarios, such as women in the 1st trimester of pregnancy, travelers to pandemic areas, and personnel taking care of infected patients. Longer protection from PVP can be achieved through repeated infusion or gene therapy. In this project, I will engineer PVP against Zika virus. Successful completion of this project will lay the foundation of a new generation of prophylaxis against many pathogens, especially those with proven difficulty to vaccine development, such as HIV and dengue virus. In addition, unlike conventional vaccines, which rely on the host immune system to produce the protective antibody and/or T cells, and are often less effective among people with weakened immune system (very old and very young, immune compromised due to HIV, organ transplantation, etc.), PVP will provide similar levels of protection to anyone regardless of the health of their immune system due to the unique protective mechanism employed by PVP.

抽象的 该项目的总体目标是创建基于蛋白质的病毒预防（PVP），该预防将提供短期 （〜2-3个月）每次静脉输注后，防止各种病毒感染的保护。这种PVP方法 灵感来自生态源源理论，该理论指出有机体在景观中的种群 受支持（来源）或不支持（沉没）人口的栖息地的频率控制 生长。当景观中的沉没栖息地的比例超过A时，人口将下降到延伸 阈值频率。根据这种来源 - 链接理论，病毒感染在体内的传播，从有限的 局部感染（例如，直接接触感染蚊子的唾液的细胞）在很大程度上由 低于体内的水槽细胞（水槽栖息地）的阈值（景观）。中心假设 项目是，体内病毒“下沉”细胞的引入可以作为预防病毒感染的预防。在 我建议通过使用PVP功能使宿主细胞将宿主细胞转换为人造病毒下沉。这 保护持续时间（2-3个月）虽然比疫苗短得多，但会有足够的时间 在许多情况下，在许多情况下，例如怀孕1个三个月的妇女，旅行者到大流行地区， 以及照顾感染患者的人员。可以通过重复来实现更长的PVP保护 输注或基因治疗。在这个项目中，我将针对Zika病毒设计PVP。成功完成 项目将奠定新一代预防的基础，以针对许多病原体，尤其是那些病原体 事实证明，疫苗开发的困难，例如艾滋病毒和登革热病毒。此外，与传统不同 疫苗依靠宿主免疫系统产生受保护的抗体和/或T细胞，并且通常是 免疫系统弱的人中有效的效率较低（非常老，很年轻，免疫受损 由于艾滋病毒，器官移植等），PVP将为任何人提供类似的保护水平 PVP通过独特的保护机制而导致的免疫系统健康系统的健康状况。