Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence

Abstract

Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM+ or IgG1+ and continued to rise until 150 days. RBD-specific IgG+ Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.

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

“…44–46 Our study deliberately focuses on the role of MBC in those with waning or undetectable nAb to live virus, despite persistence of binding antibodies. MBC, previously identified in younger COVID-19 cohorts, 11,26,47,48 can provide a crucial back-up by responding quickly to pathogen re-encounter or vaccination to form new plasmablasts, producing potent affinity-matured antibodies with more flexible recognition of viral variants; 9,20 this is consistent with the enhanced nAb response described following vaccination of previously SARS-CoV-2 infected healthcare workers. 49 Our demonstration that B cells of relevant specificities can still be detected even when nAb titres are waning or completely abrogated provides some reassurance that a memory response remains intact in the elderly.…”

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

“…Furthermore, for severely ill patients who survive COVID-19, accumulated evidence now indicates that their titers of SARS-CoV-2-specific antibodies persist at higher levels than those of patients with milder illness. For recovered severely ill or mildly ill patients, class-switched memory B cells with accumulating SHM appear to increase in frequency in their blood for several months after the onset of symptoms and persist stably for at least 6 to 8 months, suggesting that some GC-derived clones contribute to the responses ( Dan et al., 2021 ; Hartley et al., 2020 ; Rodda et al., 2021 ; Sokal et al., 2021 ).…”

“…Data obtained from the memory B cells of convalescent SARS-CoV-2 patients in the initial 16 months of the pandemic appear to be somewhat more encouraging. One study detected RBD or N-specific memory B cells in all 25 patients of a cohort convalescing from mild, moderate, or severe COVID-19 and found that the frequency of these cells appeared to increase from the early weeks of infection to approximately 150 days PSO ( Hartley et al., 2020 ). Whether the increasing affinity of the B cells for antigen at later time points contributed to their detection was not evaluated.…”

India’s pragmatic vaccination strategy against COVID-19: a mathematical modelling-based analysis

“…For example, there is evidence that memory B cells and neutralising antibodies persist at detectable levels in blood for months postinfection. [24][25][26] Despite important recent advances in understanding implications for disease outcome on reinfection, 27 there remains much uncertainty, including on the role of the cellular immune response. 28 A recent modelling study showed how immune mechanisms could mediate a decline in the severity of COVID-19 as it becomes endemic in the coming years, 29 but it remains unclear how current licensed vaccines, in India and elsewhere, might shape these dynamics.…”