Giant MagnetoResistive (GMR) Sensors for Measuring Influenza Vaccine

用于测量流感疫苗的巨磁阻 (GMR) 传感器

• 批准号: 10317652
• 负责人: PAUL JOSEPH UTZ
• 金额: $ 15.8万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317652
• 关键词: 2019-nCoV; ATAC-seq; Affect; Aging; Antibodies; Antigens; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; B cell repertoire; Big Data; Binding; Bioinformatics; Biological; Biological Assay; Biological Markers; Biological Process; Biology; Blood specimen; CEB1 Gene; COVID-19; COVID-19 pathogenesis; COVID-19 patient; Cell surface; Clinic; Clinical; Co-Immunoprecipitations; Coagulation Process; Communicable Diseases; Complex; Coronavirus; Custom; DNA; Data Set; Development; Disease; Emerging Communicable Diseases; Endothelium; Enrollment; Evaluation; Event; Flow Cytometry; Foundations; Funding; Generations; Genes; Geography; Goals; Healthcare Systems; Hepatitis B Antibodies; Human; IFI6 gene; Immune; Immunity; Immunoglobulin G; Immunologic Monitoring; Immunology; Infection; Infectious Agent; Inflammatory Response; Influenza; Influenza vaccination; LY6E gene; Lead; Lung; Measurement; Measures; Mediating; Messenger RNA; Microfluidics; Molecular Mimicry; National Institute of Allergy and Infectious Disease; Outcome; Pathogenicity; Pathway interactions; Patient-Focused Outcomes; Patients; Peptides; Plasma; Proteins; RNA; Recovery; Research; Sampling; Serum; Signal Transduction; Skin; System; Systems Biology; T-Lymphocyte; Techniques; Technology; Testing; Transcript; Translating; Translations; Vaccination; Vaccines; Validation; Vascular Diseases; Viral; Viral Proteins; Viral Vaccines; Virus Diseases; assay development; autoinflammatory; base; biomarker panel; biomarker signature; cohort; cross reactivity; cytokine; cytokine release syndrome; endothelial dysfunction; epidemiology study; experimental study; flexibility; genetic signature; human subject; improved outcome; influenza infection; influenza virus vaccine; multidisciplinary; multiplex assay; mutant; new therapeutic target; pathogen; predicting response; predictive marker; predictive signature; priority pathogen; receptor; response; rural setting; seasonal influenza; sensor; tissue injury; transcriptome sequencing; vaccination outcome; vaccine response; vaccine trial

7. Project Summary/Abstract The overarching goal of this New Aim 4 is to test the hypothesis that SARS-CoV-2 (CoV-2) causes autoimmune disease (AI) in a subset of infected patients. Our preliminary studies on 336 COVID-19 samples from 282 COVID19 patients (four COVID-19 cohorts in three geographically distinct regions) have identified autoantibodies and clinical evidence of AI. To test the hypothesis that autoantibodies develop following CoV-2 infection, we will use autoantigen arrays to identify proteins targeted by autoantibodies, some of which may cause pathogenic inflammatory responses that could mediate lung, skin, and other tissue injury, dysregulated coagulation, endothelial dysfunction, and vasculopathy. We will then test the hypothesis that autoantibodies develop through different mechanisms including molecular mimicry and generation of receptor-blocking anti-cytokine antibodies (ACA) in response to “cytokine storm”. We hypothesize that infection with CoV-2 induces 2 different outcomes: (i) the desired outcome - protective responses that neutralize CoV-2; or (ii) pathogenic responses that lead to symptomatic autoimmunity or autoinflammatory disease. Aim 4.1 will test the hypothesis that CoV-2 causes development of autoantibodies and classifiable autoimmune diseases by leveraging our custom “COVID-19 Autoantigen Array” comprising common autoantigens from diseases that affect the lung, endothelium and skin. Aim 4.2 will characterize serum antibodies specific for proteins from CoV-2 and other coronaviruses, and correlate with autoantibodies in Aim 1, by using our “COVID-19 Viral Array” capable of simultaneously quantitating antibodies against many different wild-type and mutant viral proteins and peptides. Viral responses will be correlated with clinical outcomes including development of autoantibodies, and progression to clinical autoimmunity. Aim 4.3 will test the hypothesis that CoV-2 causes autoimmunity through mechanisms including cross-reactivity (molecular mimicry) and cytokine storm which generates receptor-blocking ACA. We will use a variety of lab-based techniques to explore these mechanisms, including purification of antigen-specific IgG from serum, co-immunoprecipitation, and cross-binding assays. Together, the proposed experiments will begin to quantify the impact of CoV-2 on AI, identify which antigens and specific AI are associated with CoV-2, and contribute to our mechanistic understanding of COVID-19 pathogenesis, setting the stage for large-scale epidemiology studies to determine the extent of autoimmunity that results from CoV-2 infection, as well as longterm impacts on the health care system and economy.

7.项目总结/摘要 新目标4的首要目标是检验SARS-CoV-2（CoV-2）导致自身免疫性疾病的假设。 感染患者子集的疾病（AI）。我们对来自282名COVID-19患者（三个地理上不同的地区的四个COVID-19队列）的336份COVID-19样本进行了初步研究， AI的临床证据为了检验CoV-2感染后产生自身抗体的假设，我们将使用 自身抗原阵列用于识别自身抗体靶向的蛋白质，其中一些可能导致致病性 炎症反应可介导肺、皮肤和其它组织损伤，凝血失调， 内皮功能障碍和血管病变。然后，我们将测试的假设，即自身抗体的发展，通过 不同的机制，包括分子模拟和受体阻断抗细胞因子抗体的产生 (ACA)以响应“细胞因子风暴”。我们假设感染CoV-2会导致两种不同的结果： (i)期望的结果-中和CoV-2的保护性反应;或（ii）导致 症状性自身免疫或自身炎性疾病。目的4.1将检验CoV-2导致 通过利用我们定制的“COVID-19”开发自身抗体和可分类的自身免疫性疾病 自体抗原阵列”包含来自影响肺、内皮和皮肤的疾病的常见自体抗原。 目标4.2将描述对CoV-2和其他冠状病毒蛋白质具有特异性的血清抗体， 与Aim 1中的自身抗体相关，通过使用我们的“COVID-19病毒阵列”， 定量针对许多不同野生型和突变病毒蛋白和肽的抗体。病毒应答 将与临床结局相关，包括自身抗体的产生和临床进展 自身免疫目的4.3将检验CoV-2通过以下机制引起自身免疫的假设： 交叉反应性（分子模拟）和产生受体阻断ACA的细胞因子风暴。我们将使用一个 各种基于实验室的技术来探索这些机制，包括纯化抗原特异性IgG， 血清、免疫共沉淀和交叉结合测定。总之，拟议的实验将开始， 量化CoV-2对AI的影响，确定哪些抗原和特定AI与CoV-2相关， 有助于我们对COVID-19发病机制的理解，为大规模的 流行病学研究，以确定由CoV-2感染引起的自身免疫的程度，以及对卫生保健系统和经济的长期影响。

项目成果

High Interferon Signature Leads to Increased STAT1/3/5 Phosphorylation in PBMCs From SLE Patients by Single Cell Mass Cytometry.

• DOI: 10.3389/fimmu.2022.833636
• 发表时间: 2022
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Yiu G;Rasmussen TK;Tsai BL;Diep VK;Haddon DJ;Tsoi J;Miller GD;Comin-Anduix B;Deleuran B;Crooks GM;Utz PJ
• 通讯作者: Utz PJ

Antigen presentation by B cells enables epitope spreading across an MHC barrier.

• DOI: 10.1038/s41467-023-42541-7
• 发表时间: 2023-10-31
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Fahlquist-Hagert, Cecilia;Wittenborn, Thomas R.;Terczynska-Dyla, Ewa;Kastberg, Kristian Savstrup;Yang, Emily;Rallistan, Alysa Nicole;Markett, Quinton Raymond;Winther, Gudrun;Fonager, Sofie;Voss, Lasse F.;Pedersen, Mathias K.;van Campen, Nina;Ferapontov, Alexey;Jensen, Lisbeth;Huang, Jinrong;Nieland, John D.;van der Poel, Cees E.;Palmfeldt, Johan;Carroll, Michael C.;Utz, Paul J.;Luo, Yonglun;Lin, Lin;Degn, Soren E.
• 通讯作者: Degn, Soren E.

Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling.

• DOI: 10.1038/s41598-018-34720-0
• 发表时间: 2018-11-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Kim K;Hall DA;Yao C;Lee JR;Ooi CC;Bechstein DJB;Guo Y;Wang SX
• 通讯作者: Wang SX

Highly sensitive detection of DNA hypermethylation in melanoma cancer cells.

• DOI: 10.1016/j.bios.2018.10.018
• 发表时间: 2019-01-15
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Nesvet J;Rizzi G;Wang SX
• 通讯作者: Wang SX