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Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Author

Listed:
  • Adam K. Wheatley

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne)

  • Jennifer A. Juno

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Jing J. Wang

    (Flinders University)

  • Kevin J. Selva

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Arnold Reynaldi

    (Kirby Institute, University of New South Wales)

  • Hyon-Xhi Tan

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Wen Shi Lee

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Kathleen M. Wragg

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Hannah G. Kelly

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne)

  • Robyn Esterbauer

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne)

  • Samantha K. Davis

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Helen E. Kent

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    Monash University)

  • Francesca L. Mordant

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Timothy E. Schlub

    (Kirby Institute, University of New South Wales
    University of Sydney)

  • David L. Gordon

    (Flinders University and SA Pathology, Flinders Medical Centre)

  • David S. Khoury

    (Kirby Institute, University of New South Wales)

  • Kanta Subbarao

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    The Peter Doherty Institute for Infection and Immunity)

  • Deborah Cromer

    (Kirby Institute, University of New South Wales)

  • Tom P. Gordon

    (Flinders University
    Department of Immunology, SA Pathology, Flinders Medical Centre)

  • Amy W. Chung

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity)

  • Miles P. Davenport

    (Kirby Institute, University of New South Wales)

  • Stephen J. Kent

    (University of Melbourne, at The Peter Doherty Institute for Infection and Immunity
    University of Melbourne
    Monash University)

Abstract

The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

Suggested Citation

  • Adam K. Wheatley & Jennifer A. Juno & Jing J. Wang & Kevin J. Selva & Arnold Reynaldi & Hyon-Xhi Tan & Wen Shi Lee & Kathleen M. Wragg & Hannah G. Kelly & Robyn Esterbauer & Samantha K. Davis & Helen , 2021. "Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21444-5
    DOI: 10.1038/s41467-021-21444-5
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    Cited by:

    1. Alessia Raineri & Thomas Radtke & Sonja Rueegg & Sarah R. Haile & Dominik Menges & Tala Ballouz & Agne Ulyte & Jan Fehr & Daniel L. Cornejo & Giuseppe Pantaleo & Céline Pellaton & Craig Fenwick & Milo, 2023. "Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Alexandra B. Hogan & Patrick Doohan & Sean L. Wu & Daniela Olivera Mesa & Jaspreet Toor & Oliver J. Watson & Peter Winskill & Giovanni Charles & Gregory Barnsley & Eleanor M. Riley & David S. Khoury &, 2023. "Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Jia Wei & Philippa C. Matthews & Nicole Stoesser & Thomas Maddox & Luke Lorenzi & Ruth Studley & John I. Bell & John N. Newton & Jeremy Farrar & Ian Diamond & Emma Rourke & Alison Howarth & Brian D. M, 2021. "Anti-spike antibody response to natural SARS-CoV-2 infection in the general population," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Khadija Khan & Gila Lustig & Cornelius Römer & Kajal Reedoy & Zesuliwe Jule & Farina Karim & Yashica Ganga & Mallory Bernstein & Zainab Baig & Laurelle Jackson & Boitshoko Mahlangu & Anele Mnguni & Ay, 2023. "Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    5. Hanna Renk & Alex Dulovic & Alina Seidel & Matthias Becker & Dorit Fabricius & Maria Zernickel & Daniel Junker & Rüdiger Groß & Janis Müller & Alexander Hilger & Sebastian F. N. Bode & Linus Fritsch &, 2022. "Robust and durable serological response following pediatric SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Irene A. Abela & Chloé Pasin & Magdalena Schwarzmüller & Selina Epp & Michèle E. Sickmann & Merle M. Schanz & Peter Rusert & Jacqueline Weber & Stefan Schmutz & Annette Audigé & Liridona Maliqi & Anni, 2021. "Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    7. Farina Karim & Catherine Riou & Mallory Bernstein & Zesuliwe Jule & Gila Lustig & Strauss Graan & Roanne S. Keeton & Janine-Lee Upton & Yashica Ganga & Khadija Khan & Kajal Reedoy & Matilda Mazibuko &, 2024. "Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Deborah Cromer & Megan Steain & Arnold Reynaldi & Timothy E. Schlub & Shanchita R. Khan & Sarah C. Sasson & Stephen J. Kent & David S. Khoury & Miles P. Davenport, 2023. "Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    9. Dominik Menges & Kyra D. Zens & Tala Ballouz & Nicole Caduff & Daniel Llanas-Cornejo & Hélène E. Aschmann & Anja Domenghino & Céline Pellaton & Matthieu Perreau & Craig Fenwick & Giuseppe Pantaleo & C, 2022. "Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Robert W. Aldridge & Alexei Yavlinsky & Vincent Nguyen & Max T. Eyre & Madhumita Shrotri & Annalan M. D. Navaratnam & Sarah Beale & Isobel Braithwaite & Thomas Byrne & Jana Kovar & Ellen Fragaszy & Wi, 2022. "SARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    11. Adriana Tomic & Donal T. Skelly & Ane Ogbe & Daniel O’Connor & Matthew Pace & Emily Adland & Frances Alexander & Mohammad Ali & Kirk Allott & M. Azim Ansari & Sandra Belij-Rammerstorfer & Sagida Bibi , 2022. "Divergent trajectories of antiviral memory after SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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