Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2
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Abstract
Background
While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined.
Methods
We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action.
Results
To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion.
Conclusions
Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.
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SciScore for 10.1101/2021.08.06.21261710: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Human subject research was approved by both the Johns Hopkins University School of Medicine’s Institutional Review Board and the Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects.
Consent: All participants provided written informed consent.Sex as a biological variable not detected. Randomization In the permutation test procedure, the penalized multivariate regression was performed against randomized functional outcomes in the JHMI cohort in a 200-time repeated fashion. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: IgG, IgA, and IgM levels of each selected sample were evaluated with and without IgM depletion by … SciScore for 10.1101/2021.08.06.21261710: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Human subject research was approved by both the Johns Hopkins University School of Medicine’s Institutional Review Board and the Dartmouth-Hitchcock Medical Center Committee for the Protection of Human Subjects.
Consent: All participants provided written informed consent.Sex as a biological variable not detected. Randomization In the permutation test procedure, the penalized multivariate regression was performed against randomized functional outcomes in the JHMI cohort in a 200-time repeated fashion. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: IgG, IgA, and IgM levels of each selected sample were evaluated with and without IgM depletion by multiplex assay as described above26,43,74. Table 2: Resources
Software and Algorithms Sentences Resources Data analysis and visualization: Basic analysis and visualization were performed using GraphPad Prism. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Other limitations include the use of surrogate functional assays that bear advantages in terms of throughput and reproducibility but pose limitations in terms of their biological relevance. As further functional assays reliant on free virions and infected cells are developed, it will be of interest to compare and contrast both the degree of correlation with these convenient proxy assays as well as to model those activities in pursuit of insights into unique subpopulations of antibodies that may be responsible for their induction, or to define general characteristics of a response that is highly polyfunctional. As viral variants continue to emerge, rapid binding profiling may be an important complement to functional breadth assessments. Insights into how Fc characteristics of cross-reactive responses relate to diverse functions may provide accelerated insights into population-level susceptibility and support prioritization among candidate vaccine regimens. Numerous randomized clinical trials of convalescent plasma for COVID-19 are in the process of completion and it is likely that plasma remnants will be available for retrospective detailed serological analysis and correlation with clinical outcome15. This multivariate analysis provides a blueprint for carrying out such investigation, which could provide information on the antibody functions that contribute to clinical efficacy. The discovery of antibody functions associated with passive antibody efficacy could allow optimizat...
Results from TrialIdentifier: No clinical trial numbers were referenced.
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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