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

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.

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2

“…SN-HCW could have become PCR negative by recruitment, however, non-seroconverters after PCR positivity were rare (2.6% of PCR+ HCW negative by all 3 seroassays 16 ) and antibody responses are unlikely to have waned before recruitment 28 . Furthermore, SN-HCW lacked detectable SARS-CoV-2 spike-specific memory B-cells, which we have shown persist after waning of nAb 29 (Extended Data Fig. 1b, below detection threshold).…”

“…Multiparameter flow cytometry was used for ex vivo identification of spike-specific memory B cells staining as previously described 29 . Biotinylated tetrameric spike ( 29 .…”

“…Multiparameter flow cytometry was used for ex vivo identification of spike-specific memory B cells staining as previously described 29 . Biotinylated tetrameric spike ( 29 . The magnitude of the SARS-CoV-2 spike-specific memory B cell population is expressed as a percentage of memory B cells (gated as: lymphocytes, singlets, Live, CD3-CD14-CD19+, CD20+, excluding: CD38 hi , IgD+ and CD27+CD21-) binding both PE-and APC-labelled spike.…”

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2 infection

“…Some may have been infected before recruitment but non-seroconverters after PCR positivity were rare (only 2.6% of PCR+ HCW were negative by all 3 serological tests 21 ), and antibody responses were unlikely to have waned before study recruitment 36 . Furthermore staining ES with dual-colour tetramers showed they lacked detectable SARS-CoV-2 spike-specific memory B cells, which we have shown persist after waning of nAb 37 (example plots Extended Data Fig. 1b, comparable frequency to pre-pandemics [below the threshold of detection 37 ], Fig.…”

“…Multiparameter flow cytometry was used for ex vivo identification of spike-specific memory B cells staining as previously described 37…”