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Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen specific clones.
Scharf, Lydia; Axelsson, Hannes; Emmanouilidi, Aikaterini; Mathew, Nimitha R; Sheward, Daniel J; Leach, Susannah; Isakson, Pauline; Smirnov, Ilya V; Marklund, Emelie; Miron, Nicolae; Andersson, Lars-Magnus; Gisslén, Magnus; Murrell, Ben; Lundgren, Anna; Bemark, Mats; Angeletti, Davide.
  • Scharf L; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Axelsson H; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Emmanouilidi A; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Mathew NR; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Sheward DJ; Department of Microbiology, Tumor and Cell Biology, Karolinska Insitute, Stockholm, Sweden.
  • Leach S; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Isakson P; Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Smirnov IV; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Marklund E; Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
  • Miron N; Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Andersson LM; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Gisslén M; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Murrell B; Department of Microbiology, Tumor and Cell Biology, Karolinska Insitutet, Sotckholm, Sweden.
  • Lundgren A; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Bemark M; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
  • Angeletti D; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
JCI Insight ; 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2235313
ABSTRACT
Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from severe COVID-19 patients every third to seventh day during hospitalization and every third month after recovery. We profiled the antigen-specific immune cell dynamics by combining single cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-Seq, B cell receptor (BCR)-Seq with oligo-tagged antigen baits. While the proportion of Spike Receptor Binding Domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen specific cells, which was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to one year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen specific B cell responses in longitudinally sampled COVID-19 infected patients.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines / Variants Language: English Year: 2022 Document Type: Article Affiliation country: Jci.insight.165299

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines / Variants Language: English Year: 2022 Document Type: Article Affiliation country: Jci.insight.165299