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

2021 ◽  
Author(s):  
Anna Jeffery-Smith ◽  
Alice R Burton ◽  
Sabela Lens ◽  
Chloe Rees-Spear ◽  
Monika Patel ◽  
...  
Keyword(s):  
B Cells ◽  
Elderly Care ◽  
Care Home ◽  
The Elderly ◽  
Memory B Cells ◽  
Careful Monitoring ◽  
Neutralising Antibodies ◽  
Specific Memory ◽  
Cell Immunity ◽  
Vulnerable Elderly

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.

scholarly journals SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralising antibodies

2021 ◽  
Author(s):  
Anna Jeffery-Smith ◽  
Alice R. Burton ◽  
Sabela Lens ◽  
Chloe Rees-Spear ◽  
Jessica Davies ◽  
...  
Keyword(s):  
B Cells ◽  
The Elderly ◽  
Memory B Cells ◽  
Neutralising Antibodies ◽  
Specific Memory

The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly

Vaccine ◽  
2010 ◽  
Vol 28 (30) ◽  
pp. 4763-4770 ◽  
Author(s):  
Helen E. Baxendale ◽  
Sheila M. Keating ◽  
Marina Johnson ◽  
Jo Southern ◽  
Elizabeth Miller ◽  
...  
Keyword(s):  
B Cells ◽  
The Elderly ◽  
Memory B Cells ◽  
Specific Memory ◽  
Kinetics Of

scholarly journals Evidence of SARS-Cov-2-specific memory B cells six months after vaccination with BNT162b2 mRNA vaccine

2021 ◽  
Author(s):  
Annalisa Ciabattini ◽  
Gabiria Pastore ◽  
Fabio Fiorino ◽  
Jacopo Polvere ◽  
Simone Lucchesi ◽  
...  
Keyword(s):  
B Cells ◽  
Memory B Cells ◽  
Limited Information ◽  
Specific Memory ◽  
Cell Immunity ◽  
Antibody Titers ◽  
Specific Igg ◽  
Humoral Responses

SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cells generation and long-term persistence. Here, we investigated Spike-specific memory B cells and humoral responses in 145 subjects, up to six months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibody titers peaked 7 days after the second dose and significant titers and neutralizing activity were still observed after six months, despite a progressive decline over time. Concomitant to antibody reduction, Spike-specific memory B cells, mostly IgG class-switched, increased in blood of vaccinees and persisted six months after vaccination. Following in vitro restimulation, circulating memory B cells reactivated and produced Spike-specific antibodies. A high frequency of Spike-specific IgG+ plasmablasts, identified by computational analysis 7 days after boost, positively correlated with the generation of IgG+ memory B cells at six months. These data demonstrate that mRNA BNT162b2 vaccine elicits strong B cell immunity with Spike-specific memory B cells that still persist six months after vaccination, playing a crucial role for rapid response to SARS-CoV-2 virus encounter.

scholarly journals Long-term persistence of neutralizing memory B cells in SARS-CoV-2

2020 ◽  
Author(s):  
Rowena Bull ◽  
Arunasingam Abayasingam ◽  
Harikrishnan Balachandran ◽  
David Agapiou ◽  
Chaturaka Rodrigo ◽  
...  
Keyword(s):  
B Cells ◽  
Protective Immunity ◽  
Memory B Cells ◽  
Cell Repertoire ◽  
Neutralising Antibodies ◽  
Specific Memory ◽  
B Cell Repertoire ◽  
Antibody Titres ◽  
Selected Subset

Abstract Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 have been raised, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitored antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres were maintained, half of the cohort’s neutralising responses had returned to background. However, encouragingly in a selected subset of 13 participants, 12 had detectable RBD-specific memory B cells and these generally increased out to 6 months. Furthermore, we were able to generate monoclonal antibodies with SARS-CoV-2 neutralising capacity from these memory B cells. Overall our study suggests that the loss of neutralising antibodies in plasma may be countered by the maintenance of neutralising capacity in the memory B cell repertoire.

scholarly journals Evidence of SARS-CoV-2-Specific Memory B Cells Six Months After Vaccination With the BNT162b2 mRNA Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Annalisa Ciabattini ◽  
Gabiria Pastore ◽  
Fabio Fiorino ◽  
Jacopo Polvere ◽  
Simone Lucchesi ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Limited Information ◽  
Specific Antibodies ◽  
Specific Memory ◽  
Cell Immunity ◽  
Antibody Titers ◽  
Humoral Responses

SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cell generation and long-term persistence. Here, we investigated spike-specific memory B cells and humoral responses in 145 subjects, up to 6 months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibodies peaked 7 days after the second dose and significant antibody titers and ACE2/RBD binding inhibiting activity were still observed after 6 months, despite a progressive decline over time. Concomitant to antibody reduction, spike-specific memory B cells, mostly IgG class-switched, increased in the blood of vaccinees and persisted 6 months after vaccination. Following the in vitro restimulation, circulating memory B cells reactivated and produced spike-specific antibodies. A high frequency of spike-specific IgG+ plasmablasts, identified by computational analysis 7 days after boost, positively correlated with the generation of IgG+ memory B cells at 6 months. These data demonstrate that mRNA BNT162b2 vaccine elicits strong B cell immunity with spike-specific memory B cells that still persist 6 months after vaccination, playing a crucial role for a rapid response to SARS-CoV-2 virus encounter.

An optimized assay for the enumeration of antigen-specific memory B cells in different compartments of the human body

2010 ◽  
Vol 358 (1-2) ◽  
pp. 56-65 ◽  
Author(s):  
Yanran Cao ◽  
Maja Gordic ◽  
Sebastian Kobold ◽  
Nesrine Lajmi ◽  
Sabrina Meyer ◽  
...  
Keyword(s):  
B Cells ◽  
Human Body ◽  
Memory B Cells ◽  
Specific Memory

scholarly journals Induction of long-lived germinal centers associated with persisting antigen after viral infection.

1996 ◽  
Vol 183 (5) ◽  
pp. 2259-2269 ◽  
Author(s):  
M F Bachmann ◽  
B Odermatt ◽  
H Hengartner ◽  
R M Zinkernagel
Keyword(s):  
T Cell ◽  
B Cells ◽  
Viral Infection ◽  
Neutralizing Antibody ◽  
Germinal Centers ◽  
Memory B Cells ◽  
Specific Memory ◽  
Specific Amplification ◽  
Antibody Levels ◽  
Red Pulp

Vesicular stomatitis virus (VSV) induces an early T cell-independent neutralizing lgM response that is followed by a long-lived, T cell-dependent lgG response. We used the specific amplification factor of several 100x of VSV-virions for immunohistology to analyze the localization of VSV-specific B cells at different time points after immunization. At the peak of the IgM response (day 4), VSV-specific B cells were predominantly present in the red pulp and marginal zone but not in the T area. These B cells were mostly stained in the cytoplasm, characterizing them as antibody secreting cells. By day 6 after immunization, germinal centers (GC) containing surface-stained VSV-specific B cells became detectable and were fully established by day 12. At the same time, large VSV-specific B cell aggregates were present in the red pulp. High numbers of VSV-specific GC associated with persisting antigen were present 1 mo after immunization and later, i.e., considerably longer than has been observed for haptens. Some GC, exhibiting follicular dendritic cells and containing VSV-specific, proliferating B cells were still detectable up to 100 d after immunization. Long-lived GC were also observed after immunization with recombinant VSV-glycoprotein in absence of adjuvants. Thus some anti-virally protective (memory) B cells are cycling and locally proliferate in long-lived GC in association with persisting antigen and therefore seem responsible for long-term maintenance of elevated antibody levels. These observations extend earlier studies with carrier hapten antigens in adjuvant depots or complexed with specific IgG; they are the first to show colocalization of antigen and specific memory B cells and to analyze a protective neutralizing antibody response against an acute viral infection.

scholarly journals COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection

2021 ◽  
Author(s):  
Pablo Garcia-Valtanen ◽  
Christopher Martin Hope ◽  
Makutiro Ghislain Masavuli ◽  
Arthur Eng Lip Yeow ◽  
Harikrishnan Balachandran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Post Infection ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Pseudotyped Virus ◽  
Cell Responses ◽  
Specific Memory ◽  
Cell Functionality

Background The duration and magnitude of SARS-CoV-2 immunity after infection, especially with regard to the emergence of new variants of concern (VoC), remains unclear. Here, immune memory to primary infection and immunity to VoC was assessed in mild-COVID-19 convalescents one year after infection and in the absence of viral re-exposure or COVID-19 vaccination. Methods Serum and PBMC were collected from mild-COVID-19 convalescents at ~6 and 12 months after a COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15-40). Serum titers of RBD and Spike-specific Ig were quantified by ELISA. Virus neutralisation was assessed against homologous, pseudotyped virus and homologous and VoC live viruses. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped by activation-induced marker assay, while T cell functionality was assessed by intracellular cytokine staining using peptides specific to homologous Spike virus antigen and four VoC Spike antigens. Findings At 12 months after mild-COVID-19, >90% of convalescents remained seropositive for RBD-IgG and 88.9% had circulating RBD-specific memory B cells. Despite this, only 51.2% convalescents had serum neutralising activity against homologous live-SARS-CoV-2 virus, which decreased to 44.2% when tested against live B.1.1.7, 4.6% against B.1.351, 11.6% against P.1 and 16.2%, against B.1.617.2 VoC. Spike and non-Spike-specific T cells were detected in >50% of convalescents with frequency values higher for Spike antigen (95% CI, 0.29-0.68% in CD4+ and 0.11-0.35% in CD8+ T cells), compared to non-Spike antigens. Despite the high prevalence and maintenance of Spike-specific T cells in Spike 'high-responder' convalescents at 12 months, T cell functionality, measured by cytokine expression after stimulation with Spike epitopes corresponding to VoC was severely affected. Interpretations SARS-CoV-2 immunity is retained in a significant proportion of mild COVID-19 convalescents 12 months post-infection in the absence of re-exposure to the virus. Despite this, changes in the amino acid sequence of the Spike antigen that are present in current VoC result in virus evasion of neutralising antibodies, as well as evasion of functional T cell responses.

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