Bovine colostrum-derived antibodies against SARS-CoV-2 show great potential to serve as prophylactic agents

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum immediately before calving. Here, we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks the interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persisted on the nasal mucosa for at least 4 hours, as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for rapid and versatile adaptation for preparing prophylactic treatments against other diseases using the defined characteristics of antibody movement into the colostrum.

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  1. SciScore for 10.1101/2021.06.08.21258069: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Immunization of pregnant cows: All animal experimental protocols were approved by the Estonian Project Authorization Committee for Animal Experiments on November 5th 2020 (approval number 177), and all experiments were performed in accordance with the European Communities Directive of September 2010 (2010/63/EU) and the study was carried out in compliance with the ARRIVE guidelines.
    IACUC: Immunization of pregnant cows: All animal experimental protocols were approved by the Estonian Project Authorization Committee for Animal Experiments on November 5th 2020 (approval number 177), and all experiments were performed in accordance with the European Communities Directive of September 2010 (2010/63/EU) and the study was carried out in compliance with the ARRIVE guidelines.
    IRB: Bioavailability of colostrum immunoglobulin preparation: To test the nasal biological availability of the bovine colostrum immunoglobulin preparation a clinical study on 16 healthy volunteers was conducted in accordance with the Declaration of Helsinki, approval was granted by the Tartu University Ethics Committee on March 17th 2021 (approval number 336/T-1) and the and the trial was registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT04916574).
    Consent: Written informed consent was obtained from each healthy volunteer.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Pseudovirus neutralization assay: HEK293 cells were co-transfected via electroporation with ACE2 encoding DNA fragment and Hygromycin encoding DNA, and grown in DMEM in the presence of 200 µg/mL Hygromycin for 2 weeks for selection.
    HEK293
    suggested: None
    Next, 4× 104 Vero E6 cells were added to each well and the plates were incubated for 4 days at 37°C in humid environment before evaluation of the cytopathic effect caused by viral infection.
    Vero E6
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04916574CompletedClinical Trial of BioBlock COVID-19 Nasal Spray Containing A…


    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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