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SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies

Anna Jeffery-Smith, Alice R Burton, Sabela Lens, Chloe Rees-Spear, Monika Patel, Robin Gopal, Luke Muir, Felicity Aiano, Katie J Doores, J. Yimmy Chow, Shamez N Ladhani, Maria Zambon, Laura E McCoy, Mala K Maini
doi: https://doi.org/10.1101/2021.05.30.446322
Anna Jeffery-Smith
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
2Virus Reference Department, Public Health England, United Kingdom
3Blizard Institute, Queen Mary University of London, United Kingdom
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Alice R Burton
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
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Sabela Lens
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
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Chloe Rees-Spear
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
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Monika Patel
2Virus Reference Department, Public Health England, United Kingdom
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Robin Gopal
2Virus Reference Department, Public Health England, United Kingdom
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Luke Muir
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
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Felicity Aiano
4Immunisation and Countermeasures Division, Public Health England, United Kingdom
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Katie J Doores
5Department of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London, London, UK
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J. Yimmy Chow
6London Coronavirus Response Cell, Public Health England, United Kingdom
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Shamez N Ladhani
4Immunisation and Countermeasures Division, Public Health England, United Kingdom
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Maria Zambon
2Virus Reference Department, Public Health England, United Kingdom
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Laura E McCoy
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
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Mala K Maini
1Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, United Kingdom
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  • For correspondence: m.maini@ucl.ac.uk
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Abstract

Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of vulnerable elderly care home residents and younger staff, a high proportion of whom had lost neutralising antibodies (nAb), to investigate their reserve immunity from SARS-CoV-2-specific MBC. Class-switched spike and RBD-tetramer-binding MBC with a classical phenotype persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly, particularly to RBD. Our findings demonstrate persistence of SARS-CoV-2-specific MBC beyond loss of nAb, but highlight the need for careful monitoring of functional defects in RBD-specific B cell immunity in the elderly.

One sentence summary Circulating class-switched spike and RBD-specific memory B cells can outlast detectable neutralising antibodies but are functionally constrained in the elderly.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Joint senior authors

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 31, 2021.
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SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies
Anna Jeffery-Smith, Alice R Burton, Sabela Lens, Chloe Rees-Spear, Monika Patel, Robin Gopal, Luke Muir, Felicity Aiano, Katie J Doores, J. Yimmy Chow, Shamez N Ladhani, Maria Zambon, Laura E McCoy, Mala K Maini
bioRxiv 2021.05.30.446322; doi: https://doi.org/10.1101/2021.05.30.446322
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SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies
Anna Jeffery-Smith, Alice R Burton, Sabela Lens, Chloe Rees-Spear, Monika Patel, Robin Gopal, Luke Muir, Felicity Aiano, Katie J Doores, J. Yimmy Chow, Shamez N Ladhani, Maria Zambon, Laura E McCoy, Mala K Maini
bioRxiv 2021.05.30.446322; doi: https://doi.org/10.1101/2021.05.30.446322

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