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.

Highlights

  • The human coronavirus SARS-CoV-2 has had a devastating impact on the elderly, who are at much greater risk of morbidity and mortality [1,2]

  • SARS-CoV2 spike and RBD-specific memory B cells can persist after loss of neutralising antibodies

  • In this study we sampled a cohort of very elderly residents and younger staff who developed mild/asymptomatic SARS-CoV-2 infection during care home outbreaks, a high proportion of whom had lost neutralising antibodies (nAb) by five months

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Summary

Introduction

The human coronavirus SARS-CoV-2 has had a devastating impact on the elderly, who are at much greater risk of morbidity and mortality [1,2]. Whether older survivors of SARS-CoV-2 infection are able to mount robust and durable responses with the potential to provide long-term protection from reinfection, and from emerging viral variants, remains to be understood. In the months following infection with other viruses, including human coronaviruses like SARS-CoV-2, neutralising antibodies continue to wane and can drop below the threshold of detection in a proportion of individuals [3,8,9,10,11,12,13]. Antibody responses of inadequate titre or unable to cross-recognise variants can be compensated by a second line of defence provided by antigen-specific memory B cells (MBC), that are poised to react rapidly upon pathogen re-encounter or vaccine boosting [17,18,19]. Can MBC provide a faster response on re-exposure to the virus, they are able to diversify in the face of a mutating virus, resulting in more potent, affinity-matured antibody response and enhanced resistance to viral mutations [9,20]

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