Regulation of Pathogenic Plasma Cells in Human SLE

人类系统性红斑狼疮致病性浆细胞的调控

• 批准号: 10187509
• 负责人: Ignacio E. Sanz
• 金额: $ 174.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-19 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10187509
• 关键词: Acute; Address; Adult; Airway Disease; Antibodies; Antibody Response; Antigens; B-Lymphocytes; Biological Assay; Blood; Blood specimen; Borrelia burgdorferi; COVID-19; COVID-19 pandemic; Cells; Clostridium difficile; Collaborations; Color; Coronavirus; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Excision; Freezing; Goals; Gold; Health; Health Personnel; Human; Immune; Immune response; Immunity; Immunoassay; Immunoglobulin-Secreting Cells; Immunology procedure; Infection; Influenza; Investigation; Laboratories; Lead; Legal patent; Licensing; Lower Respiratory Tract Infection; Lyme Disease; Lyme Infection; Nose; Nucleocapsid Proteins; Pathogenicity; Patients; Peptides; Plasma Cells; Pneumonia; Proteins; Quarantine; Recording of previous events; Regulation; Resolution; Respiratory Failure; Respiratory syncytial virus; Risk; Sampling; Serum; Severe Acute Respiratory Syndrome; Staphylococcus aureus; Streptococcus pneumoniae; Swab; Systemic Lupus Erythematosus; Technology; Testing; Time; Universities; Vaccines; Validation; Viral; Viral Load result; Virus; Virus Diseases; acute infection; base; commercialization; follow-up; influenzavirus; microbial; neutralizing monoclonal antibodies; novel; novel diagnostics; outcome forecast; pandemic disease; respiratory; response

Novel Immune Diagnostics of COVID-19 for Acute Infection, Prognosis of Severe Disease, and Resolution of Infection. The spreading COVID-19 pandemic has once again highlighted the need to develop better diagnostic tests and vaccines geared towards the enhancement of effective B cell responses and passive therapies through the administration of neutralizing monoclonal antibodies. Our application, will directly address the development of novel immune assays to diagnose acute COVID-19 infection, provide prognosis of patients who may develop severe respiratory complications, and identify immunity and disease resolution in asymptomatic adults during the course of this pandemic. Our laboratories with expertise in B cells and plasma cell responses to vaccines and influenza virus infections provide the basis for a novel diagnostic platform that interrogates circulating antibody secreting cells (ASC) when a patient is ill. This technology can diagnose the following microbial infections: Influenza virus, Respiratory syncytial virus (RSV) 1,2, Streptococcus pneumoniae, Staphylococcus aureus 3 , Clostridioides difficile (C. difficile) (Haddad et al, in review), and Borrelia burgdorferi (Lyme disease). Originally performed with fresh blood ASC in cumbersome Elispot immunoassays, Drs. Daiss and Lee at MicroB-plex, Inc. have streamlined the assay into a patented technology that utilizes a cultured supernatant of newly secreted antibodies from isolated blood ASC. The novel matrix is MENSA, a “media enriched with newly synthesized antibodies” and can be easily multiplexed with over 10-12 antigens (as shown in preliminary data). The cell free-MENSA matrix can be easily collected and frozen to evaluate the contemporaneous ASC responses at the time of illness. In addition, a negative MENSA after diagnosis can demonstrate viral clearance and resolution of the active immune response. In this supplement, we propose to develop a novel immune-based COVID-19 MENSA assay (1) to diagnose acute infection and (2) and to prognosticate patients at risk of respiratory failure. In addition, with resolution of infection, a negative COVID-19 MENSA and positive serum test will show immunity with disease resolution. All tests will be available for commercialization without a need for licensing specific for this COVID19 pandemic.

COVID-19 的新型免疫诊断用于急性感染、严重疾病的预后以及 感染的解决。 COVID-19 大流行的蔓延再次凸显了开发更好的诊断测试和 旨在通过以下方式增强有效 B 细胞反应和被动疗法的疫苗 我们的应用将直接解决中和单克隆抗体的开发问题。 用于诊断急性 COVID-19 感染的新型免疫测定，为可能出现感染的患者提供预后 严重的呼吸道并发症，并确定无症状成人的免疫力和疾病缓解情况 这次大流行的过程。 我们的实验室在 B 细胞和浆细胞对疫苗和流感病毒感染的反应方面拥有专业知识 为新型诊断平台提供基础，该平台可在以下情况下询问循环抗体分泌细胞（ASC）： 该技术可以诊断患者生病了以下微生物感染：流感病毒、呼吸道病毒。 合胞病毒 (RSV) 1,2、肺炎链球菌、金黄色葡萄球菌 3 , 艰难梭菌 (C. difficile) （Haddad 等人，评论中）和伯氏疏螺旋体（莱姆病）最初是在新鲜血液 ASC 中进行的。 MicroB-plex, Inc. 的 Daiss 和 Lee 博士将繁琐的 Elispot 免疫分析简化为 专利技术利用从分离的血液 ASC 中新分泌的抗体的培养上清液。 这种新型基质是 MENSA，一种“富含新合成抗体的介质”，可以轻松进行多重化 具有超过 10-12 种抗原（如初步数据所示），可以轻松收集和使用无细胞 MENSA 基质。 冷冻以评估患病时的同期 ASC 反应。此外，MENSA 呈阴性。 诊断后可以证明病毒清除和主动免疫反应的解决。 作为补充，我们建议开发一种新型的基于免疫的 COVID-19 MENSA 检测 (1) 来诊断急性 感染和（2）并预测患者有呼吸衰竭的风险。 感染、COVID-19 MENSA 阴性和血清检测阳性将显示对疾病的免疫力 所有测试都可用于商业化，无需针对此次新冠病毒大流行获得专门许可。