SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity

  1. M. Gordon Joyce
  2. Wei-Hung Chen
  3. Rajeshwer S. Sankhala
  4. Agnes Hajduczki
  5. Paul V. Thomas
  6. Misook Choe
  7. Elizabeth J. Martinez
  8. William C. Chang
  9. Caroline E. Peterson
  10. Elaine B. Morrison
  11. Clayton Smith
  12. Rita E. Chen
  13. Aslaa Ahmed
  14. Lindsay Wieczorek
  15. Alexander Anderson
  16. James Brett Case
  17. Yifan Li
  18. Therese Oertel
  19. Lorean Rosado
  20. Akshaya Ganesh
  21. Connor Whalen
  22. Joshua M. Carmen
  23. Letzibeth Mendez-Rivera
  24. Christopher P. Karch
  25. Neelakshi Gohain
  26. Zuzana Villar
  27. David McCurdy
  28. Zoltan Beck
  29. Jiae Kim
  30. Shikha Shrivastava
  31. Ousman Jobe
  32. Vincent Dussupt
  33. Sebastian Molnar
  34. Ursula Tran
  35. Chandrika B. Kannadka
  36. Sandrine Soman
  37. Caitlin Kuklis
  38. Michelle Zemil
  39. Htet Khanh
  40. Weimin Wu
  41. Matthew A. Cole
  42. Debra K. Duso
  43. Larry W. Kummer
  44. Tricia J. Lang
  45. Shania E. Muncil
  46. Jeffrey R. Currier
  47. Shelly J. Krebs
  48. Victoria R. Polonis
  49. Saravanan Rajan
  50. Patrick M. McTamney
  51. Mark T. Esser
  52. William W. Reiley
  53. Morgane Rolland
  54. Natalia de Val
  55. Michael S. Diamond
  56. Gregory D. Gromowski
  57. Gary R. Matyas
  58. Mangala Rao
  59. Nelson L. Michael
  60. Kayvon Modjarrad

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Abstract

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  1. Version published to 10.1016/j.celrep.2021.110143
  2. ScreenIT

    SciScore for 10.1101/2021.05.09.443331: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: The research protocol was approved by the Institutional Animal Care and Use Committee of WRAIR.
    Sex as a biological variableEach study group was composed of 10 hACE2 K18 Tg mice (5 males and 5 females).
    RandomizationMice were randomly assigned to experimental groups and were not pre-screened or selected based on size or other gross physical characteristics.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For the antibodies, plasmids encoding heavy and light chains of antibodies (CR3022, and SR1-SR5) were co-transfected into Expi293F cells (ThermoFisher) according to the manufacturer’s instructions for expression of antibodies.
    CR3022
    suggested: (Imported from the IEDB Cat# CR3022, RRID:AB_2848080)
    SARS-COV-2 antibodies were immobilized onto AHC biosensors (FortéBio) for 100 seconds, followed by a brief baseline in assay buffer for 15 s.
    SARS-COV-2
    suggested: None
    Antibody positive (anti-RBD mouse mAb; BEI resources) and negative controls were included on each plate.
    anti-RBD
    suggested: None
    The secondary antibodies were HRP-conjugated AffiniPure Goat Anti-Mouse antibodies from Jackson ImmunoResearch specific for either Fcγ subclass 1, Fcγ subclass 2a, or Fcγ subclass 2c.
    Anti-Mouse
    suggested: None
    Fcγ subclass 1 , Fcγ subclass 2a , or Fcγ subclass 2c .
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Infectivity and neutralization titers were determined using ACE2-expressing HEK293 target cells (Integral Molecular) in a semi-automated assay format using robotic liquid handling (Biomek NXp Beckman Coulter).
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Virus was passaged once in Vero CCL81 cells (ATCC) and titrated by focus-forming assay on Vero E6 cells.
    Vero CCL81
    suggested: None
    Serum-virus mixtures were then added to Vero E6 cells in 96-well plates and incubated for 1 h at 37°C.
    Vero E6
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    BALB/c and C57BL/6 mice were obtained from Jackson Laboratories (Bar Harbor, ME).
    BALB/c
    suggested: None
    For the passive immunization study, on day −1, K18-hACE2 mice were injected intravenously with purified IgG from C57BL/6 vaccinated mice.
    K18-hACE2
    suggested: RRID:IMSR_GPT:T037657)
    C57BL/6
    suggested: None
    Recombinant DNA
    SentencesResources
    The His-tagged SARS-CoV-2 RBD molecule was generated by amplifying the RBD domain from the RBD-Ferritin plasmid while encoding the 3’ purification tag and subcloned into the CMVR vector.
    RBD-Ferritin
    suggested: None
    SARS-CoV-2 pseudovirions (PSV) were produced by co-transfection of HEK293T/17 cells with a SARS-CoV-2 S plasmid (pcDNA3.4) and an HIV-1 NL4-3 luciferase reporter plasmid (The reagent was obtained through the NIH HIV Reagent Program, Division of AIDS, NIAID,
    pcDNA3.4
    suggested: RRID:Addgene_131198)
    Human Immunodeficiency Virus 1 (HIV-1) NL4-3 ΔEnv Vpr Luciferase Reporter Vector (pNL4-3.Luc.R-E-), ARP-3418, contributed by Dr. Nathaniel Landau and Aaron Diamond).
    pNL4-3.Luc.R-E-
    suggested: None
    Software and Algorithms
    SentencesResources
    S-domain ferritin nanoparticle fusions were modelled using Pymol and Coot (Emsley et al., 2010) and expanded using “phenix.apply_ncs” (Liebschner et al., 2019).
    Coot
    suggested: (Coot, RRID:SCR_014222)
    Visual analysis and figure generation was conducted using ChimeraX and PyMOL.
    ChimeraX
    suggested: (UCSF ChimeraX, RRID:SCR_015872)
    PyMOL
    suggested: (PyMOL, RRID:SCR_000305)
    Grids were imaged using a FEI T20 operating at 200 kV with an Eagle 4K CCD using SerialEM or using a Thermo Scientific Talos L120C operating at 120 kV with Thermo Scientific Ceta using EPU.
    SerialEM
    suggested: (SerialEM, RRID:SCR_017293)
    RELION 3.1.1, and/or cisTEM-1.0.0-beta.
    RELION
    suggested: (RELION, RRID:SCR_016274)
    CTF estimation was done with CTFFIND 4.1.13 and used for 2D classification.
    CTFFIND
    suggested: (CTFFIND, RRID:SCR_016732)
    Purified research grade nanoparticle immunogens were formulated in PBS with 5% glycerol at 1 mg/ml and subsequently diluted with dPBS (Quality Biological) to provide 10 μg or lower amount per 50 μl dose upon mixing with adjuvant.
    Quality Biological
    suggested: None
    Spike-Ferritin nanoparticle immunogens were formulated with ALFQ to contain 20 μg 3D-PHAD and 10 μg QS21 per 50 μl dose.
    ALFQ
    suggested: (aLFQ, RRID:SCR_005925)
    SARS-CoV-2 pseudovirions (PSV) were produced by co-transfection of HEK293T/17 cells with a SARS-CoV-2 S plasmid (pcDNA3.4) and an HIV-1 NL4-3 luciferase reporter plasmid (The reagent was obtained through the NIH HIV Reagent Program, Division of AIDS, NIAID,
    HIV Reagent Program
    suggested: None
    Assay equivalency for SARS-CoV-2 was established by participation in the SARS-CoV-2 Neutralizing Assay Concordance Survey (SNACS) run by the Virology Quality Assurance Program and External Quality Assurance Program Oversite Laboratory (EQAPOL) at the Duke Human Vaccine Institute, sponsored through programs supported by the National Institute of Allergy and Infectious Diseases, Division of AIDS.
    Quality Assurance Program
    suggested: None
    Quality Assurance Program Oversite Laboratory
    suggested: None
    Neutralization curves were generated using Prism software (GraphPad Prism 8.0).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    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
    NCT03186781CompletedInfluenza HA Ferritin Vaccine, Alone or in Prime-Boost Regim…
    NCT03814720CompletedDose, Safety, Tolerability and Immunogenicity of an Influenz…
    NCT04579250RecruitingDose, Safety, Tolerability and Immunogenicity of an Influenz…
    NCT04645147RecruitingSafety and Immunogenicity of an Epstein-Barr Virus (EBV) gp3…
    NCT04296279RecruitingA Trial For The Study of Falciparum Malaria Protein 014 Admi…
    NCT04784767RecruitingSARS-COV-2-Spike-Ferritin-Nanoparticle (SpFN) Vaccine With 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

    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 10.1101/2021.05.09.443331v1 on bioRxiv