Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes

Abstract: Development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 SARS-CoV-2-specific monoclonal Abs (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an NTD-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy chain-dominant binding pattern seen in other NTD supersite-specific neutralizing Abs with much narrower specificity. We also report the discovery of CC24.2, a pan-sarbecovirus neutralizing antibody that targets a novel RBD epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 protects in vivo, suggesting potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.
Datasets: This repository contains the 10x Genomic cellranger outputs (matrix and vdj contig files) as well as complied functional characterization dataset used to generate figures on the publication "Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes". 
Post-vaccination samples for donors CC10, CC25, CC31, CC66 were processed in single 10x Genomic reactions. The timepoints samples consist of multiplexing donors CC10, CC25, CC31, CC66 into one 10x Genomic reaction. Similarly, donors CC26, CC42, CC62, CC67 were multiplexed into a single 10x Genomic reaction.
Files:
feature names.csv - csv file with sort bait/antigen barcode key 
feature_reference.csv - csv file with cell hash and antigen barcode reference
filtered_contig_annotations.csv - High-level annotations of each high-confidence contigs from cell-associated barcodes. This is a subset of all_contig_annotations.csv.
filtered_contig.fasta - filtered antibody fasta
filtered_matrix.mtx.gz - 10x Genomic matrix file for filtered cells. Contains counts data for feature and gene expression library.
raw_matrix.mtx.gz - 10x Genomic matrix file for unfiltered cells. Contains counts data for feature and gene expression library.
Code: All code used to generate analysis and figures is available under the MIT license on Github