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