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一种基于蛋白质的病毒预防（PVP），它将提供短期 每次静脉输注后（约 2-3 个月）可防止各种病毒感染。 受到生态源汇理论的启发，该理论指出景观中有机体的种群 受支持（源）或不支持（下沉）其种群的栖息地的频率控制 当景观中汇栖息地的比例超过时，人口就会减少并走向灭绝。 根据这种源汇理论，病毒感染在体内的传播，是从有限度开始的。 局部感染（例如细胞直接接触受感染蚊子的唾液）主要是由 低于体内库细胞（库栖息地）的阈值（景观）。 该项目的目的是在体内引入病毒“库”细胞可以预防病毒感染。 在这个项目中，我建议通过用 PVP 对其进行功能化，将宿主细胞转化为人工病毒库。 保护持续时间（2-3个月）虽然比疫苗短得多，但仍能提供足够的保护 在许多情况下提供保护，例如怀孕第一个三个月的妇女、前往疫区的旅行者、 和照顾受感染患者的人员可以通过重复进行更长时间的 PVP 防护。 在这个项目中，我将设计抗寨卡病毒的 PVP。 该项目将为针对多种病原体的新一代预防奠定基础，特别是那些具有以下特征的病原体： 此外，与传统疫苗不同的是，艾滋病毒和登革热病毒等疫苗的开发已被证明存在困难。 疫苗依赖宿主免疫系统产生保护性抗体和/或 T 细胞，通常 对于免疫系统较弱的人（非常年老和非常年轻，免疫受损）效果较差 由于艾滋病毒、移植器官等），PVP 将为任何人提供类似水平的保护，无论其情况如何 由于 PVP 采用的独特保护机制，他们的免疫系统健康。

项目成果

Golden Gate assembly with a bi-directional promoter (GBid): A simple, scalable method for phage display Fab library creation.

具有双向启动子 (GBid) 的 Golden Gate 组装：一种简单、可扩展的噬菌体展示 Fab 文库创建方法。

• 发表时间: 2020
• 影响因子: 4.6
• 作者: Chockalingam, Karuppiah;Peng, Zeyu;Vuong, Christine N;Berghman, Luc R;Chen, Zhilei
• 通讯作者: Chen, Zhilei

Potent and pan-neutralization of SARS-CoV-2 variants of concern by DARPins.

DARPins 对所关注的 SARS-CoV-2 变体进行有效和泛中和。

• 发表时间: 2022-05-31
• 作者: Chonira, Vikas;Kwon, Young Do;Gorman, Jason;Case, James Brett;Ku, Zhiqiang;Simeon, Rudo;Casner, Ryan G;Harris, Darcy R;Olia, Adam S;Stephens, Tyler;Shapiro, Lawrence;Boyd, Hannah;Tsybovsky, Yaroslav;Krammer, Florian;Diamond, Michael S;Kwong
• 通讯作者: Kwong