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SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies.

Jeffery-Smith, A; Burton, AR; Lens, S; Rees-Spear, C; Davies, J; Patel, M; Gopal, R; Muir, L; Aiano, F; Doores, KJ; et al. Jeffery-Smith, A; Burton, AR; Lens, S; Rees-Spear, C; Davies, J; Patel, M; Gopal, R; Muir, L; Aiano, F; Doores, KJ; Chow, JY; Ladhani, SN; Zambon, M; McCoy, LE; Maini, MK (2022) SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies. J Clin Invest, 132 (2). e152042. ISSN 0021-9738 https://doi.org/10.1172/JCI152042
SGUL Authors: Ladhani, Shamez Nizarali

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Abstract

Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2-specific MBCs in this setting. Class-switched spike and receptor-binding domain (RBD) tetramer-binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein- (S1-), and RBD-specific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2-specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD-specific B cell immunity in the elderly.

Item Type: Article
Additional Information: © 2022, Jeffery-Smith et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Keywords: Adaptive immunity, COVID-19, Immunoglobulins, Immunology, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, Female, Humans, Immunoglobulin Class Switching, Immunologic Memory, Male, Memory B Cells, SARS-CoV-2, Spike Glycoprotein, Coronavirus
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Clin Invest
ISSN: 0021-9738
Language: eng
Media of Output: Print
Related URLs:
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
26603Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
MC_PC_20060Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/R008698/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/V028448/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
URI: https://openaccess.sgul.ac.uk/id/eprint/117585
Publisher's version: https://doi.org/10.1172/JCI152042

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