Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection

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Abstract

Deep mutational scanning shows that the mRNA-1273 RBD-binding antibody response is less affected by single viral mutations than the infection response.

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  1. SciScore for 10.1101/2021.04.14.439844: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Due to the de-identified nature of the samples, the work described in this paper was deemed non-human subjects research by the Fred Hutchinson Cancer Research Center Institutional Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    All data from this cohort (i.e., the neutralization and RBD- and spike-binding activity of plasmas pre- and post-depletion of RBD-binding antibodies in Fig. 1 and RBD-binding escape maps in Fig. 4, S6B, and S7) were previously reported (15) with the exception of neutralization assays in Fig. 5, S8, and S9, which were newly performed in this study.
    S6B
    suggested: None
    S9
    suggested: None
    After the serum incubations, the libraries were secondarily labeled with 1:100 FITC-conjugated anti-MYC antibody (Immunology Consultants Lab, CYMC-45F) to label for RBD expression and 1:200 Alexa-647-conjugated goat anti-human-IgA+IgG+IgM (Jackson ImmunoResearch 109-605-064) to label for bound serum antibodies.
    anti-MYC
    suggested: None
    anti-human-IgA+IgG+IgM
    suggested: None
    Magnetic Separation Rack, ThermoFisher CS15000) was used to separate antibodies that bind RBD from the supernatant, and the supernatant (the post-RBD antibody depletion sample) was removed.
    post-RBD
    suggested: None
    Dilution series of the “synthetic” sera comprised of the anti-RBD antibody rREGN10987 (49) or anti-NTD antibody r4A8 (21) and pooled pre-pandemic human serum from 2017-2018 (Gemini Biosciences; nos. 100–110, lot H86W03J; pooled from 75 donors) were performed such that the anti-spike antibody was present at a highest concentration of 0.25 μg/mL.
    anti-RBD
    suggested: None
    anti-NTD
    suggested: None
    anti-spike
    suggested: None
    Antibody binding was detected with TMB/E HRP substrate (Millipore Sigma, ES001) and 1 N HCl was used to stop the reaction.
    ES001
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell lines: HEK-293T (ATCC CRL-3216) cells were used to generate SARS-CoV-2 spike-pseudotyped lentiviral particles and 293T-ACE2 cells (BEI NR-52511) were used to titer the SARS-CoV-2 spike-pseudotyped lentiviral particles and to perform neutralization assays (see
    HEK-293T
    suggested: ATCC Cat# CRL-3216, RRID:CVCL_0063)
    293T-ACE2
    suggested: RRID:CVCL_YZ65)
    Software and Algorithms
    SentencesResources
    Magnetic beads conjugated to the SARS-CoV-2 RBD (AcroBiosystems, MBS-K002) were prepared according to the manufacturer’s protocol.
    AcroBiosystems
    suggested: (ACRObiosystems, RRID:SCR_012550)

    Results from OddPub: Thank you for sharing your code and data.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A caveat is that some differences could also be because the vaccinated individuals were relatively young (18–55 years) and healthy, whereas the convalescent individuals were older (23–76 years, median 56) with a range of comorbidities (13). More generally, our findings suggest that it is important to differentiate antibody immunity acquired by different means when assessing the impact of viral evolution. Significant effort is being expended to identify emerging antigenic variants of SARS-CoV-2 and determine which ones might evade immunity (3, 7, 8, 33). Our findings suggest that the results could vary depending on the source of immunity. Furthermore, carefully characterizing and comparing the specificity of antibody immunity elicited by additional vaccine modalities could provide a basis for determining whether some will be more resistant to viral evolution.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04283461Active, not recruitingSafety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1…


    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.

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