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      Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets

      1 , 14 , 1 , 14 , 2 , 14 , 2 , 3 , 4 , 2 , 2 , 1 , 5 , 2 , 2 , 2 , 2 , 6 , x , 7 , 7 , 8 , 9 , 2 , , 2 , 1 , 3 , 6 , 6 , 6 , 10 , 11 , 10 , 11 , 12 , 9 , 6 , x , y , 6 , 4 , 13 , 1 , 2 , 15 ,
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          Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we utilized single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post-symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.

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          Dugan et al. utilize a multi-antigen bait sorting and single cell sequencing approach to profile B cell immunodominance upon SARS-CoV-2 infection, revealing a dynamic response that evolves toward internal virus proteins over time. Antibodies to internal proteins were non-protective in vivo, suggesting vaccination may generate superior anti-spike immunological memory.

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          Author and article information

          Elsevier Inc.
          6 May 2021
          6 May 2021
          [1 ]Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
          [2 ]University of Chicago Department of Medicine, Section of Rheumatology, Chicago, IL 60637, USA
          [3 ]Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA
          [4 ]Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711
          [5 ]Section of Genetic Medicine, University of Chicago, Chicago, IL 60637, USA
          [6 ]Departments of Medicine, Washington University School of Medicine, St Louis, MO 63130, USA
          [x ]Pathology and Immunology, and Washington University School of Medicine, St Louis, MO 63130, USA
          [y ]Molecular Immunology, Washington University School of Medicine, St Louis, MO 63130, USA
          [7 ]University of Chicago Department of Surgery, Chicago, IL 60637, USA
          [8 ]University of Chicago Department of Medicine, Chicago, IL 60637, USA
          [9 ]Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
          [10 ]Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL 60637, USA
          [11 ]Structural Biology Center, X-ray Science Division, Argonne National Laboratory, Lemont, IL 60439, USA
          [12 ]Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA
          [13 ]Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639 Tokyo, Japan
          Author notes
          []Corresponding author (P.C.W.)

          These authors contributed equally.


          Lead Contact.


          Current address: School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand.

          © 2021 Elsevier Inc.

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          : 17 February 2021
          : 6 April 2021
          : 29 April 2021



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