{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T21:45:19Z","timestamp":1774475119502,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100015976","name":"State Key Laboratory of Pathogen and Biosecurity","doi-asserted-by":"publisher","award":["SKLPBS2138"],"award-info":[{"award-number":["SKLPBS2138"]}],"id":[{"id":"10.13039\/501100015976","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174531"],"award-info":[{"award-number":["82174531"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Project","award":["JCYJ20180507183842516"],"award-info":[{"award-number":["JCYJ20180507183842516"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Coronavirus disease 2019 pandemic continues globally with a growing number of infections, but there are currently no effective antibody drugs against the virus. In addition, 90% amino acid sequence identity between the S2 subunit of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV S proteins attracts us to examine S2-targeted cross-neutralizing antibodies that are not yet well defined. We therefore immunized RenMab mice with the full-length S protein and constructed a high-throughput antibody discovery method based on single-cell sequencing technology to isolate SARS-CoV-2 S-targeted neutralizing antibodies and cross-neutralizing antibodies against the S2 region of SARS-CoV-2\/SARS-CoV S. Diversity of antibody sequences in RenMab mice and consistency in B-cell immune responses between RenMab mice and humans enabled screening of fully human virus-neutralizing antibodies. From all the frequency &amp;gt;1 paired clonotypes obtained from single-cell V(D)J sequencing, 215 antibodies with binding affinities were identified and primarily bound S2. However, only two receptor-binding domain-targeted clonotypes had neutralizing activity against SARS-CoV-2. Moreover, 5' single-cell RNA sequencing indicated that these sorted splenic B cells are mainly plasmablasts, germinal center (GC)-dependent memory B-cells and GC B-cells. Among them, plasmablasts and GC-dependent memory B-cells were considered the most significant possibility of producing virus-specific antibodies. Altogether, using a high-throughput single cell-based antibody discovery approach, our study highlighted the challenges of developing S2-binding neutralizing antibodies against SARS-CoV-2 and provided a novel direction for the enrichment of antigen-specific B-cells.<\/jats:p>","DOI":"10.1093\/bib\/bbac070","type":"journal-article","created":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T20:08:54Z","timestamp":1644696534000},"source":"Crossref","is-referenced-by-count":6,"title":["A high-throughput single cell-based antibody discovery approach against the full-length SARS-CoV-2 spike protein suggests a lack of neutralizing antibodies targeting the highly conserved S2 domain"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-6296","authenticated-orcid":false,"given":"Mengya","family":"Chai","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, 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