A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection

  1. Andreas Herrmann
  2. Junki Maruyama
  3. Chanyu Yue
  4. Christoph Lahtz
  5. Heyue Zhou
  6. Lisa Kerwin
  7. Whenzong Guo
  8. Yanliang Zhang
  9. William Soo Hoo
  10. Soonpin Yei
  11. Sunkuk Kwon
  12. Yanwen Fu
  13. Sachi Johnson
  14. Arthur Ledesma
  15. Yiran Zhou
  16. Yingcong Zhuang
  17. Elena Yei
  18. Tomasz Adamus
  19. Slobodan Praessler
  20. Henry Ji

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Abstract

Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcγR + antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro . The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by FcγR + antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcγR + antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo . Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations.

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  2. Rapid Reviews Infectious Diseases

    Niren Murthy

    Review 1: "A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection"

    Study claims the S1-Fc vaccine provides protective activity against COVID-19 live infection. Given the urgent need for a vaccine, this data is worth publishing but the study has some defects, including the need for controls to enhance the quality of the study.

  3. Rapid Reviews Infectious Diseases

    Pamela Silver, Jeffrey Way

    Review 2: "A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection"

    Study claims the S1-Fc vaccine provides protective activity against COVID-19 live infection. Given the urgent need for a vaccine, this data is worth publishing but the study has some defects, including the need for controls to enhance the quality of the study.

  4. ScreenIT

    SciScore for 10.1101/2020.06.29.178616: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Study approval: Mouse care and experimental procedures with mice were performed under pathogen-free conditions in accordance with established institutional guidance and approved Animal Care and Use Protocols (ACUP) from the Research Animal Care Committee at Sorrento Therapeutics Inc.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableMice and cell culture: For intramuscular antigen challenge, C57BL/6 female mice 5-6 weeks old were injected with either 100 μg rS1-Fc, or electroporation was applied delivering 2 μg, 20 μg, or 50 μg linear dsDNA encoding S1-Fc.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of anti-SARS-CoV-2 Spike S1-domain specific serum antibody: A direct binding ELISA format was used to detect the anti-SARS-CoV-2 Spike S1 Subunit antibody in mouse serum samples.
    anti-SARS-CoV-2 Spike S1-domain
    suggested: None
    anti-SARS-CoV-2
    suggested: None
    The plate was washed 3 times prior to adding 50 μl of 1:1000 diluted Goat anti-Mouse IgG H+L-HRP antibody (Bio-Rad, Cat# 172-1011) to the plate and incubated for 1 h at RT, 300 rpm.
    anti-Mouse IgG
    suggested: (Bio-Rad Cat# 172-1011, RRID:AB_11125936)
    Upon blocking tissue with PBS containing 10 % mouse serum and 2.5% goat serum for 1 h at RT, primary antibodies against S1 or dendritic cell marker (clone 33D1) were incubated diluted in blocking buffer in a wet chamber over night at 4°C.
    S1
    suggested: None
    Cells were blocked with CD16/CD32 and incubated for 30 min on ice with FITC-, PE-, APC-, PECy7-, PerCP-Cy5.5, BV421, BV605, BV 650, and BV785-conjugated surface-staining antibodies (CD3, CD4, CD8, CD69, CD19, CD11c, CD80, CD86, and F4/80), followed by intracellular staining antibodies (IL-4, IFNγ, and S1) 30 min on ice, purchased from Biolegend, or in-house.
    BV421
    suggested: None
    BV785-conjugated surface-staining
    suggested: None
    CD3
    suggested: (GenWay Biotech Inc. Cat# GWB-220B7B, RRID:AB_10511043)
    CD4
    suggested: (GenWay Biotech Inc. Cat# GWB-2D09B7, RRID:AB_10264023)
    CD8
    suggested: (GenWay Biotech Inc. Cat# GWB-40E1B7, RRID:AB_10514761)
    CD69
    suggested: (BD Biosciences Cat# 558063, RRID:AB_2275535)
    CD19
    suggested: (GenWay Biotech Inc. Cat# GWB-B7A22E, RRID:AB_10528952)
    CD11c
    suggested: None
    CD80
    suggested: None
    CD86
    suggested: None
    IL-4, IFNγ
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Murine NIH/3T3 fibroblasts, C2C12 myoblasts and 264.7 RAW macrophages were obtained from ATCC and subcultured according to the vendor’s instructions.
    NIH/3T3
    suggested: ATCC Cat# CRL-6361, RRID:CVCL_6662)
    C2C12
    suggested: None
    Confluent Vero E6 cells in 96-well plates were inoculated with 100 µl of the virus-serum mixture.
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    For intramuscular antigen challenge, C57BL/6 female mice were injected with 100 μg rS1-Fc intravenously.
    C57BL/6
    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 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.
    • 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.

  5. Version published to 10.1101/2020.06.29.178616v1 on bioRxiv