Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

  1. Séverin Coléon
  2. Aurélie Wiedemann
  3. Mathieu Surénaud
  4. Christine Lacabaratz
  5. Sophie Hue
  6. Mélanie Prague
  7. Minerva Cervantes-Gonzalez
  8. Zhiqing Wang
  9. Jerome Ellis
  10. Amandine Sansoni
  11. Camille Pierini
  12. Quentin Bardin
  13. Manon Fabregue
  14. Sarah Sharkaoui
  15. Philippe Hoest
  16. Léa Dupaty
  17. Florence Picard
  18. Marwa El Hajj
  19. Mireille Centlivre
  20. Jade Ghosn
  21. Rodolphe Thiébaut
  22. Sylvain Cardinaud
  23. Bernard Malissen
  24. Gérard Zurawski
  25. Ana Zarubica
  26. Sandra M. Zurawski
  27. Véronique Godot
  28. Yves Lévy

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Abstract

No abstract available

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  1. Version published to 10.1016/j.ebiom.2022.104062
  2. ScreenIT

    SciScore for 10.1101/2021.12.28.474244: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: All animal procedures (including surgery, anesthesia, and euthanasia, as applicable) used in the current study were submitted to the Institutional Animal Care and Use Committee of the CIPHE approved by the French authorities (CETEA DSV – APAFIS#26484-2020062213431976 v6).
    IRB: Ethics approval was given on February 5, 2020, by the French Ethics Committee CPP-Ile-de-France VI (ID RCB: 2020-A00256-33).
    Consent: The study was conducted with the understanding and consent of each participant or their surrogate covering the sampling, storage, and use of biological samples.
    Sex as a biological variableVaccination and infection of hCD40/K18-hACE2 transgenic mice: Mice of 8 to 12 weeks of age of both sexes received two intraperitoneal injections of the CD40.CoV2 vaccine (10 µg) plus polyinosinic-polycytidylic acid (Poly-IC; Oncovir) (50 µg) or poly(IC) alone three weeks apart.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Materials availability: The CD40.CoV2 vaccine generated in this study was deposited in GenBank: anti-human CD40 12E12 antibody IgG4 H chain (GenBank ID: AJD85779.1 residues 20-467) fused to SARS_CoV_2RBD (GenBank ID: UEP92470.1 residues 17-240) followed by EPEA (C-tag) and the anti-human CD40 12E12 antibody kappa L chain (GenBank ID: AJD85780.1 residues 21-236) fused sequentially to a linker (GenBank ID: AJD85777.1 residues 699-725), nucleocapsid phosphoprotein, partial [Severe acute respiratory syndrome coronavirus 2] (GenBank ID: QWE63393.1 residues 95-230), linker residues AR, Chain A, Spike protein S1 [Severe acute respiratory syndrome coronavirus 2] (GenBank ID: 7M8J_A residues 113-237), linker residues TR, and Sequence 12 from patent US 8518410
    C-tag
    suggested: None
    [IgG] Kits, MesoScale Discovery, Rockville, MD, USA) were used on all available plasma samples to measure plasma IgG antibodies to SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoVs.
    plasma IgG
    suggested: None
    Antibody concentrations were quantified using a reference standard (ACE2 Calibration Reagent) and are expressed as units/mL (one unit per mL concentration of ACE2 Calibration Reagent corresponds to neutralizing activity of 1 µg/mL monoclonal antibody to SARS-CoV-2 Spike protein).
    SARS-CoV-2 Spike protein) .
    suggested: None
    The flow cytometry panel included a viability marker, CD3, CD4, and CD8 to determine the T-cell lineage, and IFN-γ, TNF, and IL-2 antibodies.
    CD3
    suggested: None
    CD4
    suggested: None
    CD8
    suggested: None
    TNF
    suggested: None
    IL-2 antibodies
    suggested: None
    IL-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Infectious stocks were grown by inoculating Vero E6 cells and collecting supernatants upon observation of the cytopathic effect.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Experimental Models: Organisms/Strains
    SentencesResources
    Heterozygous K18-hACE C57BL/6J mice (strain: 2B6.Cg-Tg (K18-ACE2)2Prlmn/J) were obtained from The Jackson Laboratory.
    C57BL/6J
    suggested: RRID:MGI:3589388)
    2B6.Cg-Tg ( K18-ACE2)2Prlmn/J
    suggested: None
    For the AIM assay, PBMCs were stimulated in vitro with various concentrations of the CD40.CoV2 vaccine or an equimolar combination of 15-mer overlapping peptide pools covering the full-length sequence of vaccine antigens (vS1 + vS2 + vRBD + vN2) referred to as vOLPmix.
    vS1 + vS2 + vRBD + vN2
    suggested: None
    Software and Algorithms
    SentencesResources
    Distributions were plotted using SPICE version 5.22, downloaded from http://exon.niaid.nih.gov/spice (Roederer et al., 2011)
    SPICE
    suggested: (SPICE, RRID:SCR_016603)
    Statistical analysis: Graphpad Prism software version 8 was used for nonparametric statistics and plots, as described in the figure legends.
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study had several limitations. These included the absence of characterization of cross-neutralizing antibodies in vaccinated mice against the B.1.1.529 Omicron variant, which emerged during the writing of this manuscript. However, we could expect that our vaccine would elicit T-cell responses against N epitopes because of the high homology (100%) between vaccine sequences and this VOC. Due to the limited availability of hCD40/K18-hACE2 mice, we did not evaluate various VOC challenges in mice. Finally we favored the analysis of T cell responses using samples from recovered individuals instead of in vivo preclinical models. Although these responses may be dependent on the “clinical history” of patients and their HLA haplotypes, they are less biased than those that would be observed in an animal model. Our results show that the in-vitro vaccine responses are directed against all vaccine proteins, which confirmed the broad HLA coverage of the vaccine sequences. In conclusion, it is becoming urgent to develop a “pan-sarbecovirus vaccine”. The development of a new protein-based vaccine with expected improved tolerability suitable for people with specific vulnerabilities and children would extend the portfolio of current vaccines and be instrumental in controlling the circulation of the virus and the emergence of new variants. By selecting a narrow range of immunodominant epitopes, presented by a wide variety of HLA alleles and less prone to genetic variations across sarbecoviru...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04842682RecruitingDose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or …
    NCT04262921RecruitingFrench COVID Cohort

    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 10.1101/2021.12.28.474244v1 on bioRxiv