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.

摘要 该项目的总体目标是创建一种基于蛋白质的病毒预防（PVP）， （约2-3个月）保护，防止各种病毒感染后，每次静脉输注。这种PVP方法 受生态源-汇理论的启发，该理论指出，景观中的生物种群 是由栖息地的频率控制，要么支持（源）或不支持（汇）其人口 增长当景观中汇生境的比例超过 阈值频率根据这种源-库理论，病毒感染在体内的传播，从有限的 局部感染（例如，直接接触受感染蚊子的唾液的细胞）主要是由 低于身体（景观）中的水槽细胞（水槽栖息地）的阈值量。的中心假设 该项目的另一个目的是，在体内引入病毒“水槽”细胞可以预防病毒感染。在 在这个项目中，我提出用PVP将宿主细胞功能化，将其转化为人工病毒库。的 保护期（2-3个月），虽然比疫苗短得多， 在许多情况下的保护，如怀孕早期的妇女，前往流行地区的旅行者， 以及照顾受感染病人的人员。通过重复使用， 输注或基因治疗。在这个项目中，我将设计针对寨卡病毒的PVP。成功完成本 该项目将为新一代预防许多病原体奠定基础，特别是那些 已证明疫苗开发的困难，如艾滋病毒和登革热病毒。此外，与传统的 疫苗，其依赖于宿主免疫系统来产生保护性抗体和/或T细胞，并且通常是 在免疫系统较弱的人群中效果较差（非常年老和非常年轻，免疫功能受损 由于艾滋病毒、器官移植等），PVP将为任何人提供类似级别的保护， 由于PVP采用的独特保护机制，它们的免疫系统健康。