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Evolution of antibody immunity to SARS-CoV-2

Author

Listed:
  • Christian Gaebler

    (The Rockefeller University)

  • Zijun Wang

    (The Rockefeller University)

  • Julio C. C. Lorenzi

    (The Rockefeller University)

  • Frauke Muecksch

    (The Rockefeller University)

  • Shlomo Finkin

    (The Rockefeller University)

  • Minami Tokuyama

    (Icahn School of Medicine at Mount Sinai)

  • Alice Cho

    (The Rockefeller University)

  • Mila Jankovic

    (The Rockefeller University)

  • Dennis Schaefer-Babajew

    (The Rockefeller University)

  • Thiago Y. Oliveira

    (The Rockefeller University)

  • Melissa Cipolla

    (The Rockefeller University)

  • Charlotte Viant

    (The Rockefeller University)

  • Christopher O. Barnes

    (California Institute of Technology)

  • Yaron Bram

    (Weill Cornell Medicine)

  • Gaëlle Breton

    (The Rockefeller University)

  • Thomas Hägglöf

    (The Rockefeller University)

  • Pilar Mendoza

    (The Rockefeller University)

  • Arlene Hurley

    (The Rockefeller University)

  • Martina Turroja

    (The Rockefeller University)

  • Kristie Gordon

    (The Rockefeller University)

  • Katrina G. Millard

    (The Rockefeller University)

  • Victor Ramos

    (The Rockefeller University)

  • Fabian Schmidt

    (The Rockefeller University)

  • Yiska Weisblum

    (The Rockefeller University)

  • Divya Jha

    (Icahn School of Medicine at Mount Sinai)

  • Michael Tankelevich

    (Icahn School of Medicine at Mount Sinai)

  • Gustavo Martinez-Delgado

    (Icahn School of Medicine at Mount Sinai)

  • Jim Yee

    (Weill Cornell Medicine)

  • Roshni Patel

    (The Rockefeller University)

  • Juan Dizon

    (The Rockefeller University)

  • Cecille Unson-O’Brien

    (The Rockefeller University)

  • Irina Shimeliovich

    (The Rockefeller University)

  • Davide F. Robbiani

    (Università della Svizzera Italiana)

  • Zhen Zhao

    (Weill Cornell Medicine)

  • Anna Gazumyan

    (The Rockefeller University)

  • Robert E. Schwartz

    (Weill Cornell Medicine
    Weill Cornell Medicine)

  • Theodora Hatziioannou

    (The Rockefeller University)

  • Pamela J. Bjorkman

    (California Institute of Technology)

  • Saurabh Mehandru

    (Icahn School of Medicine at Mount Sinai)

  • Paul D. Bieniasz

    (The Rockefeller University
    The Rockefeller University)

  • Marina Caskey

    (The Rockefeller University)

  • Michel C. Nussenzweig

    (The Rockefeller University
    The Rockefeller University)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

Suggested Citation

  • Christian Gaebler & Zijun Wang & Julio C. C. Lorenzi & Frauke Muecksch & Shlomo Finkin & Minami Tokuyama & Alice Cho & Mila Jankovic & Dennis Schaefer-Babajew & Thiago Y. Oliveira & Melissa Cipolla & , 2021. "Evolution of antibody immunity to SARS-CoV-2," Nature, Nature, vol. 591(7851), pages 639-644, March.
  • Handle: RePEc:nat:nature:v:591:y:2021:i:7851:d:10.1038_s41586-021-03207-w
    DOI: 10.1038/s41586-021-03207-w
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    11. Grace Kenny & Sophie O’Reilly & Neil Wrigley Kelly & Riya Negi & Colette Gaillard & Dana Alalwan & Gurvin Saini & Tamara Alrawahneh & Nathan Francois & Matthew Angeliadis & Alejandro Abner Garcia Leon, 2023. "Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    12. Leire Campos-Mata & Benjamin Trinité & Andrea Modrego & Sonia Tejedor Vaquero & Edwards Pradenas & Anna Pons-Grífols & Natalia Rodrigo Melero & Diego Carlero & Silvia Marfil & César Santiago & Dàlia R, 2024. "A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
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    15. Meriem Bekliz & Kenneth Adea & Pauline Vetter & Christiane S. Eberhardt & Krisztina Hosszu-Fellous & Diem-Lan Vu & Olha Puhach & Manel Essaidi-Laziosi & Sophie Waldvogel-Abramowski & Caroline Stephan , 2022. "Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
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