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Longitudinal single B cell studies across the trajectory of COVID-19 to identify SARS-CoV-2 specific monoclonal antibodies and long-term memory formation

Applicant Macpherson Andrew
Number 196641
Funding scheme Special Call on Coronaviruses
Research institution Universität Bern
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.06.2020 - 31.07.2021
Approved amount 279'989.00
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Keywords (4)

monoclonal antibodies; B cells; B cell memory; humoral immunity

Lay Summary (German)

Lead
Unser Ziel ist es mit Hilfe von Sequenzierung der Antikörper-Gene auf Einzelzellebene vor, während der akuten Phase und nach genesener COVID-19 Infektion die Veränderungen der Gedächtnis B Zellen zu messen und SARS-CoV-2 spezifische Gedächtnis B Zellen zu identifizieren.
Lay summary
B Zellen sind Zellen des adaptiven Immunsystems, welche Antikörper produzieren. Jede B Zelle produziert einen eigenen Antikörper der spezifisch an einen Krankheitserreger binden kann. Nach überstandenen Infektionen können sich Gedächtnis B Zellen entwickeln die bei erneuter Infektion rasch schützende Antikörper produzieren. Zurzeit ist jedoch unklar ob sich nach überstandender SARS-CoV-2 Infektion ein Langzeit B Zell Gedächtnis entwickelt und ob es sich nur nach schwerem oder auch nach leichtem/asyomptomatischem Krankheitsverlauf ausbildet. 
Unser Ziel ist es mit Hilfe von Sequenzierung der Antikörper-Gene auf Einzelzellebene vor, während der akuten Phase und nach genesener COVID-19 Infektion die Veränderungen der Gedächtnis B Zellen zu messen und SARS-CoV-2 spezifische Gedächtnis B Zellen zu identifizieren.
Unser Projekt wird zum Verständnis dessen beitragen wie sich die B Zell Immunantwort gegen SARS-CoV-2 verhält, ob es Unterschiede zwischen schwerem und leichtem Krankheitsverlauf gibt und könnte langfristig SARS-CoV-2 spezifische neutralisierende monoklonale Antikörper identifizieren.
 
Direct link to Lay Summary Last update: 01.06.2020

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Associated projects

Number Title Start Funding scheme
123456 Molecular mechanisms of homeostatic regulation of presynaptic transmitter release 01.09.2008 Fellowships for prospective researchers

Abstract

The development of neutralizing humoral immunity is suggested to play a pivotal role in the protection from COVID-19 and the generation of immunological memory is basis for future protection from the disease. However, to date, the genetics of the acute and memory B cell response are unknown, few potential neutralizing monoclonal antibodies are described and the capacity of humans to develop B cell memory against SARS-CoV-2 is still elusive. Here we will prospectively and longitudinally follow a cohort of (>200) healthcare workers at the intestinal diseases department of the University Hospital Bern. By monitoring the course of SARS-CoV-2 infection status in this cohort, we will assess their acute and memory B cell response before, during and after COVID-19 infection. We have ethical permission to sample peripheral blood of consenting personnel and measure SARS-CoV-2 viral status weekly using in-house diagnostics with consumables that are designed not to conflict with the clinical lab pipelines. By determining the single B cell repertoire in the periphery before the onset of clinical or virus-positive disease we will be able to determine the immunological baseline for each study participant at single cell level. This baseline will be compared to acute and memory B cell populations during the active disease to identify hallmarks of the B cell repertoire associated in patients with asymptomatic, mild or severe COVID-19 infection. After resolution of the infection, subjects will be sampled at various timepoints up to half a year and the potential hallmarks of the B cell repertoire will be identified in the peripheral memory B cell pool. The data will provide a description of the acute B cell response to SARS-CoV-2 at single cell level and can determine if cellular B cell memory is formed in COVID-19 infection. We hypothesise that the data will be able to describe immunogenetic determinants of the B cell response that can discriminate between protected from non-protected individuals and/or severe from non-severe cases. Further, it will create a resource that will contribute to global databases guiding potentially neutralizing SARS-CoV-2 monoclonal antibodies.
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