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J Clin Invest . SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralising antibodies

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  • J Clin Invest . SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralising antibodies


    J Clin Invest


    . 2021 Nov 29;e152042.
    doi: 10.1172/JCI152042. Online ahead of print.
    SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralising antibodies


    Anna Jeffery-Smith 1 , Alice R Burton 1 , Sabela Lens 1 , Chloe Rees-Spear 1 , Jessica Davies 1 , Monika Patel 2 , Robin Gopal 2 , Luke Muir 1 , Felicity Aiano 3 , Katie J Doores 4 , J Yimmy Chow 5 , Shamez N Ladhani 3 , Maria Zambon 2 , Laura E McCoy 1 , Mala K Maini 1



    Affiliations

    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 elderly care home residents and younger staff (median age 87yrs and 56yrs respectively) who had survived COVID-19 outbreaks with only mild/asymptomatic infection. The cohort was selected to enrich for a high proportion who had lost neutralising antibodies (nAb), to specifically investigate the reserve immunity from SARS-CoV-2-specific MBC in this setting. Class-switched spike and RBD-tetramer-binding MBC persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike/RBD-specific MBC had a classical phenotype but activated memory B cells, that may indicate ongoing antigenic stimulation or inflammation, were expanded in the elderly. 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. Our findings demonstrate a reserve of SARS-CoV-2-specific MBC persists beyond loss of nAb, but highlight the need for careful monitoring of functional defects in spike/RBD-specific B cell immunity in the elderly.

    Keywords: Adaptive immunity; COVID-19; Immunoglobulins; Immunology.

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