Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

Xiang, Haitao; Zhao, Yang; Li, Xinyang; Li, Peipei; Wang, Longlong; Wang, Meiniang; Tian, Lei; Sun, Hai‐Xi; Zhang, Wei; Xu, Ziqian; Ye, Beiwei; Yuan, Xiaoju; Wang, Pengyan; Zhang, Ning; Gong, Yuefa; Bian, Chengrong; Wang, Zhao-Hai; Yu, Lixin; Jin, Yan; Meng, Fanping; Bai, Chunmei; Wang, Xiaoshan; Liu, Xiaopan; Gao, Kai; Wu, Liang; Liu, Longqi; Gu, Ying; Bi, Yang; Shi, Yi; Zhang, Shaogeng; Zhu, Chen; Xu, Xun; Wu, Guizhen; Gao, George F.; Yang, Naibo; Liu, William J.; Yang, Peng

doi:10.1016/j.humimm.2021.10.007

Cited by 22 publications

(20 citation statements)

References 44 publications

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“…To be able to analyze individual maturation trajectories of B cells in the primary vaccination series versus upon third vaccination, we set out to identify developmental B lineages in all individual participants and to track them across the vaccination period. A B cell lineage is a group of clonotype-defined B cells that share a common V and J gene and a CDR3 sequence differing only in up to 10% of its amino acid positions ( 30 ). While we did not detect expanding B cell lineages in a substantial proportion of participants receiving their primary vaccination series, we found expanding lineages in the majority of patients receiving their third vaccination ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

“…We identified overlapping B cell lineages in the pre- and post-vaccination time point per patient. A B cell lineage was defined as a group of B cell clonotypes that share a common V and J gene and a CDR3 sequence differing only in up to 10% of its amino acid positions ( 30 ). Lineages and their evolution were visualised as stream plots with function plot.stacked from ( ).…”

Section: Methodsmentioning

confidence: 99%

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Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination

et al. 2022

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The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging viral variants. Therefore, aiming at strong B cell somatic hypermutation to increase antibody affinity to the ancestral strain - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants since high affinity may offer some flexibility to compensate for strain-individual mutations. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the third, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination

et al. 2022

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“…Despite this, the clonotypes found to be enriched/to bear similarity to CoV-AbDab antibodies post SARS-CoV-2 exposure often differ across studies [ 20 – 22 ]. This may be partly due to the small sample sizes used in individual studies, and the intrinsic biases in individual VJ gene usage; Xiang et al .…”

Section: Introductionmentioning

confidence: 99%

“…This may be partly due to the small sample sizes used in individual studies, and the intrinsic biases in individual VJ gene usage; Xiang et al . found a larger variation between individuals within a cohort (healthy, or three different severities of COVID symptoms) than between cohorts [ 22 ]. Another contributing factor is lineage clustering itself.…”

Section: Introductionmentioning

confidence: 99%

“…Despite this, the clonotypes found to be enriched/to bear similarity to CoV-AbDab antibodies post SARS-CoV-2 exposure often differ across studies [20][21][22]. This may be partly due to the small sample sizes used in individual studies, and the intrinsic biases in individual VJ gene usage; Xiang et al found a larger variation between individuals within a cohort (healthy, or three different severities of COVID symptoms) than between cohorts [22]. Another contributing factor is lineage clustering itself.…”

Section: Introductionmentioning

confidence: 99%

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Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies

et al. 2021

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Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. Sequence-based clonal clustering can identify antibodies with similar epitope complementarity, however, antibodies from markedly different lineages but with similar structures can engage the same epitope. We describe a novel computational method for epitope profiling based on structural modelling and clustering. Using the method, we demonstrate that sequence dissimilar but functionally similar antibodies can be found across the Coronavirus Antibody Database, with high accuracy (92% of antibodies in multiple-occupancy structural clusters bind to consistent domains). Our approach functionally links antibodies with distinct genetic lineages, species origins, and coronavirus specificities. This indicates greater convergence exists in the immune responses to coronaviruses than is suggested by sequence-based approaches. Our results show that applying structural analytics to large class-specific antibody databases will enable high confidence structure-function relationships to be drawn, yielding new opportunities to identify functional convergence hitherto missed by sequence-only analysis.

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The characteristics of BCR‐CDR3 repertoire in COVID‐19 patients and SARS‐CoV‐2 vaccinated volunteers

Xiao,

Luo,

et al. 2024

Journal of Medical Virology

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The global COVID‐19 pandemic has caused more than 1 billion infections, and numerous SARS‐CoV‐2 vaccines developed rapidly have been administered over 10 billion doses. The world is continuously concerned about the cytokine storms induced by the interaction between SARS‐CoV‐2 and host, long COVID, breakthrough infections postvaccination, and the impact of SARS‐CoV‐2 variants. BCR‐CDR3 repertoire serves as a molecular target for monitoring the antiviral response “trace” of B cells, evaluating the effects, mechanisms, and memory abilities of individual responses to B cells, and has been successfully applied in analyzing the infection mechanisms, vaccine improvement, and neutralizing antibodies preparation of influenza virus, HIV, MERS, and Ebola virus. Based on research on BCR‐CDR3 repertoire of COVID‐19 patients and volunteers who received different SARS‐CoV‐2 vaccines in multiple laboratories worldwide, we focus on analyzing the characteristics and changes of BCR‐CDR3 repertoire, such as diversity, clonality, V&J genes usage and pairing, SHM, CSR, shared CDR3 clones, as well as the summary on BCR sequences targeting virus‐specific epitopes in the preparation and application research of SARS‐CoV‐2 potential therapeutic monoclonal antibodies. This review provides comparative data and new research schemes for studying the possible mechanisms of differences in B cell response between SARS‐CoV‐2 infection or vaccination, and supplies a foundation for improving vaccines after SARS‐CoV‐2 mutations and potential antibody therapy for infected individuals.

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Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

Cited by 22 publications

References 44 publications

Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination

Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination

Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies

The characteristics of BCR‐CDR3 repertoire in COVID‐19 patients and SARS‐CoV‐2 vaccinated volunteers

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