Neutralizing response against E484K variant after original SARS-CoV-2 infection

  1. Takuma Hayashi
  2. Nobuo Yaegashi
  3. Ikuo Konishi

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Abstract

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants, which are spreading in the United Kingdom (UK) and elsewhere, have been found in infected individuals in Japan. The virus mutates, to facilitate its life in the host, during the process of repeated proliferation in the body of the host, including humans. In other words, it is natural that a human-compatible mutant strain always predominates in infection and proliferation. As a result, the viral mutants acquire strong proliferative potential in the host and are highly pathogenic. The number of people infected with the mutated SARS-CoV-2 variant E484K, which is different from the SARS-CoV-2 variants that are spreading in the UK, South Africa, and Brazil, is increasing in Tokyo. It has been pointed out that the effects of immunity and vaccines may be reduced against the Tokyo-type SARS-CoV-2 variant E484K. We have investigated the neutralization response to various mutations in the spike glycoprotein using the serum of people already infected with the original SARS-CoV-2. The results showed that SARS-CoV-2 variants with Y543F or N501Y mutations in the spike glycoprotein affect the neutralization reaction. However, single E484K mutations within the spiked glycoprotein of the Tokyo-type SARS-CoV-2 variant are unlikely to have a significant effect on the affinity of the host antibody for the virus.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.07.21256803: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Participants provided written informed consent, and the study was approved by the Japan National Hospital Organization Central Ethics Review Board for Clinical Research (Meguro, Tokyo, Japan).
    IRB: Participants provided written informed consent, and the study was approved by the Japan National Hospital Organization Central Ethics Review Board for Clinical Research (Meguro, Tokyo, Japan).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    In participants with or without a prior history of COVID-19, we compared RT-PCR test or IgG/IgM antibody levels against SARS-CoV-2 proteins S and N by using two-sided Wilcoxon Mann-Whitney tests.
    IgG/IgM
    suggested: None
    Quantitative measurement of SARS-CoV-2 neutralizing antibodies: Participants were randomly contacted based on stratification into two groups: RT-PCR-positive or anti-SARS-CoV-2 IgG/IgM-positive with history of symptomatic COVID-19 (Group I) and asymptomatic COVID-19 and RT-PCR or anti-SARS-CoV-2 IgG/IgM-negative people (Group II).
    anti-SARS-CoV-2 IgG/IgM-positive
    suggested: None
    anti-SARS-CoV-2 IgG/IgM-negative
    suggested: None
    We investigated the binding of the spike glycoprotein Y453F mutant of SARS-CoV-2 to human ACE2 and determined the affinity of Y453F, N501Y, and E484K mutants of the spike glycoprotein of SARS-CoV-2 to six neutralizing monoclonal antibodies using the MOE program (three-dimensional protein structure modeling, protein-protein docking analysis: MOLSIS Inc., Tokyo, Japan) and Cn3D macromolecular structure viewer.
    N501Y
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were performed using XLSTAT version 2021.2 (Addinsoft &Vose Software, NY, USA).
    XLSTAT
    suggested: (XLSTAT, RRID:SCR_016299)

    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: 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: 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.

    About SciScore

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  2. Version published to 10.1101/2021.05.07.21256803v1 on medRxiv