Intranasal administration of SARS-CoV-2 neutralizing human antibody prevents infection in mice

  1. Hongbing Zhang
  2. Zhiyuan Yang
  3. Jingyi Xiang
  4. Ziyou Cui
  5. Jianying Liu
  6. Cheng Liu

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Abstract

Prevention of SARS-CoV-2 infection at the point of nasal entry is a novel strategy that has the potential to help contain the ongoing pandemic. Using our proprietary technologies, we have engineered a human antibody that recognizes SARS-CoV-2 S1 spike protein with an enhanced affinity for mucin to improve the antibody’s retention in respiratory mucosa. The modified antibody, when administered into mouse nostrils, was shown to block infection in mice that were exposed to high titer SARS-CoV-2 pseudovirus 10 hours after the initial antibody treatment. Our data show that the protection against SARS-CoV-2 infection is effective in both nasal and lung areas 7 days after viral exposure. The modified antibody is stable in a nasal spray formulation and maintains its SARS-CoV-2 neutralizing activity. Nasal spray of the modified antibody can be developed as an affordable and effective prophylactic product to protect people from infection by exposure to SARS-CoV-2 virus in the air.

One-sentence summary

A Fc-modified human antibody prevents SARS-CoV-2 viral infection via nasal administration

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  1. ScreenIT

    SciScore for 10.1101/2020.12.08.416677: (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 variableAnimal study: Female transgenic mice (K18-ACE2) aged 4-6 weeks were used.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Phage panning: The E-ALPHA® human scFv antibody phage display libraries (Eureka Therapeutics) were used for the selection of human antibody constructs specific to SARS-CoV-2 spike protein.
    SARS-CoV-2 spike protein.
    suggested: None
    Plates were washed three times and incubated with horseradish peroxidase (HRP)-conjugated anti-HA antibody at a 1:2000 dilution.
    anti-HA
    suggested: None
    Serial dilutions of the antibodies were incubated with SARS-CoV-2-His (2 mg/mL) for 1 hour.
    SARS-CoV-2-His (2
    suggested: None
    Following the loading step, IgG1 antibody was injected onto the Sensor Chip for 180 s at concentrations of 66.67, 33.33, 16.67, 8.33 and 4.17 nM.
    IgG1
    suggested: (James Trimmer, University of California, Davis Cat# N295B/66, RRID:AB_2750771)
    To assess EU126 IgG neutralization, pseudovirus was pre-incubated with varying concentrations of EU126 antibody for 1 hour at room temperature before adding to 293F cells expressing human ACE2.
    ACE2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The infected 293F cells were imaged by GFP fluorescence.
    293F
    suggested: RRID:CVCL_D615)
    Experimental Models: Organisms/Strains
    SentencesResources
    Animal study: Female transgenic mice (K18-ACE2) aged 4-6 weeks were used.
    Female
    suggested: None
    Software and Algorithms
    SentencesResources
    Antibody Kinetics by BiaCore: Multiple cycles of antibody binding kinetics were measured by BiaCore X100 with a Sensor Chip CAP.
    BiaCore
    suggested: (Biacore T100 System, RRID:SCR_019679)

    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.
    • No funding statement was detected.
    • 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 10.1101/2020.12.08.416677 on bioRxiv