Regulation of Pathogenic Plasma Cells in Human SLE

新型COVID-19急性感染、重症预后的免疫诊断

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.