Homologous and heterologous serological response to the N-terminal domain of SARS-CoV-2

  1. Huibin Lv
  2. Owen Tak-Yin Tsang
  3. Ray T. Y. So
  4. Yiquan Wang
  5. Meng Yuan
  6. Hejun Liu
  7. Garrick K. Yip
  8. Qi Wen Teo
  9. Yihan Lin
  10. Weiwen Liang
  11. Jinlin Wang
  12. Wilson W. Ng
  13. Ian A. Wilson
  14. J. S. Malik Peiris
  15. Nicholas C. Wu
  16. Chris K. P. Mok

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Abstract

The increasing numbers of infected cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious threats to public health and the global economy. Most SARS-CoV-2 neutralizing antibodies target the receptor binding domain (RBD) and some the N-terminal domain (NTD) of the spike protein, which is the major antigen of SARS-CoV-2. While the antibody response to RBD has been extensively characterized, the antigenicity and immunogenicity of the NTD protein are less well studied. Using 227 plasma samples from COVID-19 patients, we showed that SARS-CoV-2 NTD-specific antibodies could be induced during infection. As compared to the serological response to SARS-CoV-2 RBD, the SARS-CoV-2 NTD response is less cross-reactive with SARS-CoV. Furthermore, neutralizing antibodies are rarely elicited in a mice model when NTD is used as an immunogen. We subsequently demonstrate that NTD has an altered antigenicity when expressed alone. Overall, our results suggest that while NTD offers an alternative strategy for serology testing, it may not be suitable as an immunogen for vaccine development.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.17.431722: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All study procedures were performed after informed consent.
    IRB: The study was approved by the institutional review board of the Hong Kong West Cluster of the Hospital Authority of Hong Kong (approval number: UW20-169).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableSf9 cells (Spodoptera frugiperda ovarian cells, female) and High Five cells (Trichoplusia ni ovarian cells, female) were maintained in HyClone insect cell culture medium.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After extensive washing with PBS containing 0.1% Tween 20, each well in the plate was further incubated with the anti-human IgG secondary antibody (1:5000, Thermo Fisher Scientific) for 1 hour at 37°C.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus and Cell cultures: Vero and Vero E6 cells were maintained in DMEM medium supplemented with 10% fetal bovine serum (FBS), and 100 U mL−1 of Penicillin-Streptomycin.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Sf9 cells (Spodoptera frugiperda ovarian cells, female) and High Five cells (Trichoplusia ni ovarian cells, female) were maintained in HyClone insect cell culture medium.
    Sf9
    suggested: CLS Cat# 604328/p700_Sf9, RRID:CVCL_0549)
    Patient-derived SARS-CoV-2 (BetaCoV/Hong Kong/VM20001061/2020 [KH1]) and SARS-CoV (strain HK39849, SCoV) were passaged in Vero-E6 or Vero cells.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Experimental Models: Organisms/Strains
    SentencesResources
    Mouse immunization: 6-10 weeks BALB/c mice were immunized with two rounds either 15ug NTD protein or 105 TCID50 live viruses together with 50 μL Addavax, via intraperitoneal (i.p.) route.
    BALB/c
    suggested: None

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.02.17.431722v1 on bioRxiv