Discovery of neutralizing antibodies results from single-cell sequencing of B-cells from COVID-19 patients


By Judy Siegel-Itzkovich

A new study on single-cells sequencing of B-cells from COVID-10 patients – led by Dr. Natalia Freund in collaboration with the iReceptor Plus project and its coordinator Dr. Gur Yaari – has been published in PLoS Pathogens (under the title “Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors”) on AIRR-seq analyses of COVID-19.

These data were generated using the 10X Genomics platform and are hosted and supported by the Yaari lab and the iReceptor team. They compose the fourth repository to the AIRR Data Commons.

The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, the researchers  analyzed the B-cell responses in patients 1.5 months following SARS-CoV-2 infection.

Monoclonal antibodies cloned from donors CoV01 and CoV02

In the study, B-cell responses from severe and asymptomatic donors who recovered six weeks ago were analyzed, resulting in the isolation of six neutralizing antibodies from severely ill donors. The neutralizing antibodies are composed of frequent features that are present in naive B- cell receptor repertoires of healthy individuals and comprise up to 2.7% of all antibody heavy chain V-J combinations.

This indicates that neutralizing antibodies against SARS-CoV-2 can be produced relatively easily after vaccination or with strong viral stimulation. Such neutralizing antibodies can be used as a research tool for basic science, a diagnostic tool for rapid testing or serological measurements, a passive vaccine that can be given prophylactically in exposed individuals who are at risk or as treatment of severe disease.

The AIRR-seq dataset from six of the severely ill and seven of the mildly ill donors contains single-cell sequencing data from the donors’ B cells, using the platform of 10x Genomics (another member of iReceptor Plus) and sequenced on an Illumina NovaSeq 6000. The dataset includes about 218,000 sequences of paired heavy- and light-chain B-cell receptors, which are now publicly available and searchable through the iReceptor Gateway.