Durable SARS-CoV-2 B cell immunity after mild or severe disease.

Clinton O Ogega, Nicole E Skinner, Paul W Blair, Han-Sol Park, Kirsten Littlefield, Abhinaya Ganesan, Pranay Ladiwala, Annukka Ar Antar, Stuart C Ray, Michael J Betenbaugh, Andrew Pekosz, Sabra L Klein, Yukari C Manabe, Andrea L Cox, Justin R Bailey
Author Information
  1. Clinton O Ogega: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  2. Nicole E Skinner: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  3. Paul W Blair: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  4. Han-Sol Park: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  5. Kirsten Littlefield: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  6. Abhinaya Ganesan: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  7. Pranay Ladiwala: Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
  8. Annukka Ar Antar: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  9. Stuart C Ray: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  10. Michael J Betenbaugh: Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
  11. Andrew Pekosz: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  12. Sabra L Klein: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  13. Yukari C Manabe: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  14. Andrea L Cox: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  15. Justin R Bailey: Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Multiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease, and hospitalized patients with moderate to severe disease, at a median of 54 (39-104) days after onset of symptoms. We detected S-RBD-specific class-switched MBC in 13 out of 14 participants, including 4 of the 5 participants with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific class-switched MBC in both cohorts. FCRL5, a marker of functional memory when expressed on rMBC, was dramatically upregulated on S-RBD-specific rMBC. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched MBC that phenotypically resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after recovery from mild or severe COVID-19 disease.

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Grants

  1. U54 CA260492/NCI NIH HHS
  2. R01 AI127469/NIAID NIH HHS
  3. R21 AI151353/NIAID NIH HHS
  4. R01 NR005228/NINR NIH HHS
  5. HHSN272201400007C/NIAID NIH HHS

Word Cloud

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