Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus
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Abstract
Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects.
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SciScore for 10.1101/2021.08.19.456951: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Ebola RNA blood samples were collected from convalescent patients with viral RNA negative PCR tests in the 2014-2016 West African outbreak, three patients were Caucasian treated in the UK, and the remaining were convalescent plasma donor participants from a trial in Sierra Leone25 (consented under the Sierra Leone Ethics and Scientific Review Committee ISRCTN13990511 and PACTR201602001355272 and authorised by Pharmacy Board of Sierra Leone, #PBSL/CTAN/MOHS-CST001). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: SARS-CoV-2 protein targets) were obtained from either supplementary … SciScore for 10.1101/2021.08.19.456951: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Ebola RNA blood samples were collected from convalescent patients with viral RNA negative PCR tests in the 2014-2016 West African outbreak, three patients were Caucasian treated in the UK, and the remaining were convalescent plasma donor participants from a trial in Sierra Leone25 (consented under the Sierra Leone Ethics and Scientific Review Committee ISRCTN13990511 and PACTR201602001355272 and authorised by Pharmacy Board of Sierra Leone, #PBSL/CTAN/MOHS-CST001). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: SARS-CoV-2 protein targets) were obtained from either supplementary data files in the cited publications or by visual inspection (for PDB structures). Table 2: Resources
Antibodies Sentences Resources Healthy samples taken after SARS-CoV-2 emergence were all confirmed negative for anti-SARS-CoV-2 antibodies by SureScreen lateral flow test and by ELISA 24. anti-SARS-CoV-2suggested: NoneSoftware and Algorithms Sentences Resources Analysis of BCR clone lineage trees: Lineage trees were reconstructed using the maximum parsimony method implemented in the dnapars executable in the phylip package32. phylipsuggested: (PHYLIP, RRID:SCR_006244)This was performed using a Python implementation of the Edmond’s algorithm to construct a minimum spanning arborescence tree with the given germline V gene sequence as root. Pythonsuggested: (IPython, RRID:SCR_001658)Gene usage analysis was performed in GraphPad Prism 8.4.3 using a two-way ANOVA with a Dunnett’s post hoc test. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Data visualisation was performed using the R ggplot2 package and the following specialised R packages: visNetwork (for visualising convergent CDRH3 network clusters) and ggseqlogo (for visualising CDRH3 sequence logos). ggplot2suggested: (ggplot2, RRID:SCR_014601)PDB structures were visualised using PyMOL (version 2.3.0). PyMOLsuggested: (PyMOL, RRID:SCR_000305)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title ISRCTN13990511 NA NA Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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