A valid protective immune response elicited in rhesus macaques by an inactivated vaccine is capable of defending against SARS-CoV-2 infection

This article has been Reviewed by the following groups

Read the full article See related articles

Abstract

With the relatively serious global epidemic outbreak of SARS-CoV-2 infection, public concerns focus on not only clinical therapeutic measures and public quarantine for this disease but also the development of vaccines. The technical design of our SARS-CoV-2 inactivated vaccine provides a viral antigen that enables the exposure of more than one structural protein based upon the antibody composition of COVID-19 patients’ convalescent serum. This design led to valid immunity with increasing neutralizing antibody titers and a CTL response detected post-immunization of this vaccine by two injections in rhesus macaques. Further, this elicited immunoprotection in macaques enables not only to restrain completely viral replication in tissues of immunized animals, compared to the adjuvant control and those immunized by an RBD peptide vaccine, but also to significantly alleviate inflammatory lesion in lung tissues in histo-pathologic detection, compared to the adjuvant control with developed interstitial pneumonia. The data obtained from these macaques immunized with the inactivated vaccine or RBD peptide vaccine suggest that immunity with a clinically protective effect against SARS-CoV-2 infection should include not only specific neutralizing antibodies but also specific CTL responses against at least the S and N antigens.

Article activity feed

  1. SciScore for 10.1101/2020.08.04.235747: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableVirus and cells: The SARS-CoV-2 virus used was isolated from the respiratory secretions of an adult male patient at Yunnan Hospital of Infectious Diseases in Kunming in January 2020.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    , anti-N antibody (Snio Biological) and horseradish peroxidase (HRP)-labeled secondary antibody (Abcam, MA, USA) to visualize the proteins according to the standard protocol of the enhanced chemiluminescence (ECL) reagent
    anti-N
    suggested: None
    Electron microscopy: Purified inactivated SARS-CoV-2 preparations were coincubated with convalescent serum, a monoclonal antibody (mAb) against S (mAb-S) or N (mAb-N) (Solarbio, Beijing, China) at 37°C for 24 h, stained with 1% phosphotungstic acid and observed by transmission electron microscopy (Hitachi, Kyoto, Japan).
    mAb-N
    suggested: None
    Anti-CD3, anti-CD20 and anti-CD16 antibodies were added to the PBMCs.
    Anti-CD3 ,
    suggested: None
    anti-CD20
    suggested: None
    anti-CD16
    suggested: None
    The PBMCs were coincubated with an anti-CD4 antibody (BD) at RT for 30 min.
    anti-CD4
    suggested: None
    After incubating with the red blood cell lysis and membrane permeabilization reagents and washing with PBS twice, the cells were stained with anti-FOXP3, anti-IL-4, anti-IFN-γ and anti-IL-17A antibodies for 30 min at RT and then washed once.
    anti-FOXP3
    suggested: None
    anti-IL-4
    suggested: None
    anti-IFN-γ
    suggested: (Bio-Rad Cat# M6000007NY, RRID:AB_2784537)
    anti-IL-17A
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Vero cells were cultured in DMEM (Corning, NY, USA) containing 5% fetal bovine serum (FCS; HyClone, Logan, USA).
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    The transferred membrane was blocked in 5% bovine serum albumin (BSA)-Tris-buffered saline/Tween 20 (Tris-HCl, 100 mM, pH 7.5; NaCl, 0.9%; and Tween-20, 0.2%) and treated with convalescent serum, anti-S (Snio Biological, Beijing,
    Snio Biological
    suggested: None
    GraphPad Prism software (San Diego, CA, USA) and STATA (Version 15.0; STATA Corp., College Station, TX, USA) were used for statistical analyses.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.