Novel diagnostic tools and animal model system for study human/animal interface of COVID-19

用于研究 COVID-19 人/动物界面的新型诊断工具和动物模型系统

• 批准号: 10686156
• 负责人: Diego G Diel
• 金额: $ 76.87万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686156
• 关键词: 2019-nCoV; ACE2; Address; Animal Experiments; Animal Model; Animals; Antibodies; Area; Back; Biological Assay; Biological Models; COVID-19; COVID-19 assay; COVID-19 detection; COVID-19 diagnostic; COVID-19 pandemic; COVID-19 surveillance; COVID-19 susceptibility; Characteristics; China; Coronavirus; Data; Development; Diagnostic; Diagnostic Reagent; Disease; Dose; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Family; Family Felidae; Felis catus; Finding by Cause; General Population; Goals; Human; Illinois; Immune response; Immunize; Immunoglobulins; Immunology; Individual; Infection; International; Modeling; Molecular; Monitor; Monoclonal Antibodies; Mutation; National Institute of Allergy and Infectious Disease; Natural History; Oryctolagus cuniculus; Outcome Study; Panthera leo; Pathogenesis; Pathogenicity; Population; Prevalence; Proteins; Reagent; Research; Research Personnel; Risk; Risk Factors; SARS coronavirus; SARS-CoV-2 exposure; SARS-CoV-2 infection; SARS-CoV-2 pathogenesis; Sampling; Screening procedure; Serology test; Seroprevalences; Serum; Source; Specimen; Strategic Planning; Study models; Surveillance Program; Testing; Tigers; Time; Universities; Vaccinated; Vaccinee; Vaccines; Validation; Veterinarians; Viral; Viral Pathogenesis; Viral Proteins; Viral reservoir; Viremia; Virus; Virus Diseases; Virus Receptors; Virus Shedding; World Health Organization; Zoo Animals; animal care; animal resource; design; detection assay; diagnostic assay; diagnostic tool; epidemiology study; human disease; improved; medical countermeasure; novel; novel diagnostics; pathogen; pet animal; polyclonal antibody; public health emergency; rapid detection; rapid test; receptor; serosurveillance; success; surveillance network; therapeutic candidate; tissue tropism; tool; transmission process; vaccine candidate; viral transmission

The ongoing pandemic of COVID-19 is designated by World Health Organization (WHO) as a Public Health Emergency of International Concern. Similarities among ACE2 receptors predict that there are several animals could function as reservoirs for the virus. Recent studies by us and others identified felid animals, including domestic cats, tigers and lions as highly susceptible to SARS-CoV-2 infection. These findings cause great concerns on the potential for human to animal and animal to human transmission, along with the virus mutations that appear as the virus goes back and forth between species. One goal of this study is to design and prepare novel reagents and assays for detection and surveillance in animals. A second goal is to develop a feline animal model. Together, these data will be incorporated into models for understanding the risk of animal infection for veterinarians, other animal care professionals, and the general public. Specific Aims are: 1). To generate and characterize specific reagents for use in COVID-19 research and diagnostics; 2). To develop diagnostic assays for detecting COVID-19 virus infection in animals; 3). To establish a feline model to study SARS-CoV-2 pathogenesis; 4). To apply novel diagnostic assays in the surveillance of pets and zoo animal populations. Outcomes of this study will generate a panel of SARS-CoV- 2-specific antibody reagents, diagnostic standards, and assays for rapid detection of SARS-CoV-2 infection in all species of animals. The diagnostic assays will be applied to COVID-19 surveillance networks, which will identify important animal reservoirs. The novel serological assay can also serve as a DIVA test to differentiate between the vaccinated and infected animals (and humans). The feline pathogenesis studies will improve our understanding of viral pathogenic mechanisms, host immune responses, and provide the source of samples for early detection and test validation.

世界卫生组织 (WHO) 将持续流行的 COVID-19 指定为公共卫生事件 国际关注的紧急情况。 ACE2受体之间的相似性预测有几种动物 可以充当病毒的储存库。我们和其他人最近的研究发现了猫科动物，包括 家猫、老虎和狮子极易感染 SARS-CoV-2。这些发现引起巨大 对人与动物、动物与人之间以及病毒传播的可能性的担忧 当病毒在物种之间来回传播时出现的突变。这项研究的目标之一是设计 并制备用于动物检测和监测的新试剂和测定方法。第二个目标是 开发猫科动物模型。这些数据将被整合到模型中以供理解 兽医、其他动物护理专业人员和公众感染动物的风险。 具体目标是：1）。生成和表征用于 COVID-19 研究的特定试剂 诊断； 2）。开发检测动物 COVID-19 病毒感染的诊断方法； 3）。到 建立猫科动物模型来研究SARS-CoV-2发病机制； 4).应用新颖的诊断方法 监视宠物和动物园动物种群。这项研究的结果将产生一组 SARS-CoV- 2 特异性抗体试剂、诊断标准和快速检测 SARS-CoV-2 感染的检测方法 所有种类的动物。诊断分析将应用于 COVID-19 监测网络，这将 确定重要的动物宿主。新型血清学测定还可作为 DIVA 测试来区分 接种疫苗的动物和受感染的动物（以及人类）之间。猫科动物发病机制研究将改善我们的 了解病毒致病机制、宿主免疫反应，并提供样本来源 早期检测和测试验证。

项目成果

Infection Dynamics, Pathogenesis, and Immunity to SARS-CoV-2 in Naturally Susceptible Animal Species.

自然易感动物物种对 SARS-CoV-2 的感染动态、发病机制和免疫。

• 发表时间: 2023-10-15
• 作者: Nooruzzaman, Mohammed;Diel, Diego G
• 通讯作者: Diel, Diego G

Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals.

开发基于单克隆抗体的封闭 ELISA，用于检测动物中的 SARS-CoV-2 暴露。

• 发表时间: 2023-03-13
• 作者: Yuan, Fangfeng;Chen, Chi;Covaleda, Lina M;Martins, Mathias;Reinhart, Jennifer M;Sullivan, Drew R;Diel, Diego G;Fang, Ying
• 通讯作者: Fang, Ying

Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals.

开发基于单克隆抗体的封闭 ELISA，用于检测动物中的 SARS-CoV-2 暴露。

• 发表时间: 2023-08-24
• 影响因子: 4.8
• 作者: Yuan, Fangfeng;Chen, Chi;Covaleda, Lina M;Martins, Mathias;Reinhart, Jennifer M;Sullivan, Drew R;Diel, Diego G;Fang, Ying
• 通讯作者: Fang, Ying

The Omicron Variant BA.1.1 Presents a Lower Pathogenicity than B.1 D614G and Delta Variants in a Feline Model of SARS-CoV-2 Infection.

在 SARS-CoV-2 感染的猫科动物模型中，Omicron 变体 BA.1.1 的致病性低于 B.1 D614G 和 Delta 变体。

• 发表时间: 2022-09-14
• 作者: Martins, Mathias;do Nascimento, Gabriela M;Nooruzzaman, Mohammed;Yuan, Fangfeng;Chen, Chi;Caserta, Leonardo C;Miller, Andrew D;Whittaker, Gary R;Fang, Ying;Diel, Diego G
• 通讯作者: Diel, Diego G

The SARS-CoV-2 Spike is a virulence determinant and plays a major role on the attenuated phenotype of Omicron virus in a feline model of infection.

SARS-CoV-2 Spike 是毒力决定因素，在猫科动物感染模型中对 Omicron 病毒的减毒表型起着重要作用。

• 发表时间: 2024-03-19
• 作者: Martins, Mathias;Nooruzzaman, Mohammed;Cunningham, Jessie Lee;Ye, Chengjin;Caserta, Leonardo Cardia;Jackson, Nathaniel;Martinez;Fang, Ying;Diel, Diego G
• 通讯作者: Diel, Diego G