Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates

  1. Flavia Chiuppesi
  2. Vu H. Nguyen
  3. Yoonsuh Park
  4. Heidi Contreras
  5. Veronica Karpinski
  6. Katelyn Faircloth
  7. Jenny Nguyen
  8. Mindy Kha
  9. Daisy Johnson
  10. Joy Martinez
  11. Angelina Iniguez
  12. Qiao Zhou
  13. Teodora Kaltcheva
  14. Paul Frankel
  15. Swagata Kar
  16. Ankur Sharma
  17. Hanne Andersen
  18. Mark G. Lewis
  19. Yuriy Shostak
  20. Felix Wussow
  21. Don J. Diamond

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Abstract

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.

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  1. Version published to 10.1038/s41541-022-00436-6
  2. ScreenIT

    SciScore for 10.1101/2021.09.15.460487: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: All animal studies were conducted in compliance with local, state, and federal regulations and were approved by Bioqual and City of Hope Institutional Animal Care and Use Committees (IACUC).
    IACUC: All animal studies were conducted in compliance with local, state, and federal regulations and were approved by Bioqual and City of Hope Institutional Animal Care and Use Committees (IACUC).
    Consent: Subjects gave informed consent.
    Sex as a biological variableThirty 6-8 weeks old Syrian hamsters were randomly assigned to the groups, with 3 females and 3 males in each group.
    RandomizationThirty 6-8 weeks old Syrian hamsters were randomly assigned to the groups, with 3 females and 3 males in each group.
    BlindingBoard certified pathologists were blinded to the vaccine groups and mock controls were used as a comparator.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After washing, anti-Hamster IgG HRP secondary antibodies measuring total IgG(H+L), IgG1, or IgG2/IgG3 (Southern Biotech 6061-05, 1940-05, 1935-05) were diluted 1:1000 in blocking buffer and added to the plates.
    anti-Hamster IgG
    suggested: None
    total IgG(H+L
    suggested: None
    IgG1
    suggested: (SouthernBiotech Cat# 1940-05, RRID:AB_2795558)
    Goat anti-Monkey IgG (H+L) secondary antibody (ThermoFisher PA1-84631) was diluted 1:10,000.
    Goat anti-Monkey IgG
    suggested: (Thermo Fisher Scientific Cat# PA1-84631, RRID:AB_933605)
    anti-Monkey IgG
    suggested: (Thermo Fisher Scientific Cat# PA1-84631, RRID:AB_933605)
    Experimental Models: Cell Lines
    SentencesResources
    The stock was produced by infecting Vero E6-hACE2 cells (BEI Resources NR-53726) at low MOI with deposited passage 3 virus and resulted in a titer of 1.99×106 TCID50/ml.
    Vero E6-hACE2
    suggested: None
    The stock was generated using Vero-E6 cells infected with seed stock virus obtained from Kenneth Plante at UTMB (lot # TVP 23156).
    Vero-E6
    suggested: None
    Vero E6 cells (ATCC, CRL-1586) were seeded in 24-well plates at 175,000 cells/well in DMEM/ 10% FBS/Gentamicin.
    Vero E6
    suggested: None
    The mixture was added to 5×106 HEK293T/17 cells (ATCC CRL11268) seeded the day before in 10 cm dishes and the cells were incubated for 72h at 37°C.
    HEK293T/17
    suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)
    : Vero TMPRSS2 cells (Vaccine Research Center-NIAID) were plated at 25,000 cells/well in DMEM/10% FBS/Gentamicin.
    Vero TMPRSS2
    suggested: None
    Recombinant DNA
    SentencesResources
    PV production: SARS-CoV-2 PV was produced using a plasmid lentiviral system based on pALD-gag-pol, pALD-rev, and pALD-GFP (Aldevron)
    pALD-rev
    suggested: None
    pALD-GFP
    suggested: None
    Plasmid pALD-GFP was modified to express Firefly luciferase (pALD-Fluc)
    pALD-Fluc
    suggested: None
    Plasmid pCMV3-S (Sino Biological VG40589-UT) was used and modified to express SARS-CoV-2 Wuhan-Hu-1 S with D614G modification.
    pCMV3-S
    suggested: None
    Customized gene sequences cloned into pTwist-CMV-BetaGlobin (Twist Biosciences) were used to express SARS-CoV-2 VOC-specific S variants (Table S1).
    pTwist-CMV-BetaGlobin
    suggested: None
    Software and Algorithms
    SentencesResources
    The titers that gave 50% neutralization (NT50) were calculated by determining the linear slope of the graph plotting NT versus serum dilution by using the next higher and lower NT using Office Excel (v2019)
    Office Excel
    suggested: None
    Statistical analyses: Statistical analyses were performed using Prism 8 (GraphPad, v8.3.0).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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
    NCT04639466RecruitingA Synthetic MVA-based SARS-CoV-2 Vaccine, COH04S1, for the P…
    NCT04977024RecruitingSARS-CoV-2 Vaccine (COH04S1) Versus Emergency Use Authorizat…

    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

    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.

  3. Version published to 10.1101/2021.09.15.460487v1 on bioRxiv