A SARS-CoV-2 spike ferritin nanoparticle vaccine protects against heterologous challenge with B.1.1.7 and B.1.351 virus variants in Syrian golden hamsters

  1. Kathryn McGuckin Wuertz
  2. Erica K. Barkei
  3. Wei-Hung Chen
  4. Elizabeth J. Martinez
  5. Ines Lakhal-Naouar
  6. Linda L. Jagodzinski
  7. Dominic Paquin-Proulx
  8. Gregory D. Gromowski
  9. Isabella Swafford
  10. Akshaya Ganesh
  11. Ming Dong
  12. Xiankun Zeng
  13. Paul V. Thomas
  14. Rajeshwer S. Sankhala
  15. Agnes Hajduczki
  16. Caroline E. Peterson
  17. Caitlin Kuklis
  18. Sandrine Soman
  19. Lindsay Wieczorek
  20. Michelle Zemil
  21. Alexander Anderson
  22. Janice Darden
  23. Heather Hernandez
  24. Hannah Grove
  25. Vincent Dussupt
  26. Holly Hack
  27. Rafael de la Barrera
  28. Stasya Zarling
  29. James F. Wood
  30. Jeffrey W. Froude
  31. Matthew Gagne
  32. Amy R. Henry
  33. Elham Bayat Mokhtari
  34. Prakriti Mudvari
  35. Shelly J. Krebs
  36. Andrew S. Pekosz
  37. Jeffrey R. Currier
  38. Swagata Kar
  39. Maciel Porto
  40. Adrienne Winn
  41. Kamil Radzyminski
  42. Mark G. Lewis
  43. Sandhya Vasan
  44. Mehul Suthar
  45. Victoria R. Polonis
  46. Gary R. Matyas
  47. Eli A. Boritz
  48. Daniel C. Douek
  49. Robert A. Seder
  50. Sharon P. Daye
  51. Mangala Rao
  52. Sheila A. Peel
  53. M. Gordon Joyce
  54. Diane L. Bolton
  55. Nelson L. Michael
  56. Kayvon Modjarrad

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Abstract

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.

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  1. ScreenIT

    SciScore for 10.1101/2021.06.16.448525: (What is this?)

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

    Table 1: Rigor

    EthicsEuthanasia Agents: At study termination 6 DPC, all animals were terminally anesthetized by ketamine/xylazine, followed by exsanguination by cardiac puncture (for terminal blood collection) and euthanasia.
    IACUC: Animal protocols and procedures were reviewed and approved by the Animal Care and Use Committee of both the US Army Medical Research and Development Command (USAMRDC) Animal Care and Use Review Office as well as the Institutional Animal Care and Use Committee of Bioqual, Inc. (protocol number 20-144).
    Field Sample Permit: Oversight of all research was approved and conducted by the WRAIR Institutional Biological Safety Committee.
    Sex as a biological variableSyrian golden hamster immunizations: Male and female Syrian golden hamsters (6-8 week-old, n = 55) were acquired from Charles River Laboratories and housed at Bioqual, Inc., for the duration of the study.
    Randomizationnot detected.
    BlindingAll tissue slides were evaluated by a board-certified veterinary anatomic pathologist blinded to study group allocations.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Transfection, Expression and Purification of SpFN 1B-06-PL: Expi293 cells (Gibco, Cat No. A14527) were maintained and passaged as per manufacturer’s guidelines in Expi293 Expression Media (Gibco, Cat No. A1435101) at 37°C, 8% CO2, 120 RPM, ≥ 60% RH.
    Expi293
    suggested: RRID:CVCL_D615)
    Viral stock propagation and preparation: B.1.1.7 viral stocks were generated from seed stock (USA/CA_CDC_5574/2020), obtained from BEI resources (Cat # NR-54011, Lot # 70041598) and expanded in Calu-3 cells (incubated at 37°C for 3 days).
    Calu-3
    suggested: None
    The viral stock lot used for this study (Lot # 012921-1230) was titrated in Vero-TMPRSS2 cells, with viral titers of 1.375 × 106 PFU/mL.
    Vero-TMPRSS2
    suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)
    Briefly, hCoV-19/USA/MD-HP01542/2021 (B.1.1.351) was derived from the seed stock (Lot# MD-HP JHU P2) and propagated in in VeroE6-TMPRSS2 cells.
    VeroE6-TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    293F-Spike-S2A cells were incubated with 100 μl of plasma diluted 100-fold in RPMI containing 10% FBS (R10) for 30 minutes at 37°C.
    293F-Spike-S2A
    suggested: None
    Infectivity and neutralization titers were determined using ACE2-expressing HEK293 target cells (Integral Molecular).
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Vero TMPRSS2 cells were plated at 25,000 cells per well in DMEM supplemented with 10% FBS and gentamicin.
    Vero TMPRSS2
    suggested: None
    Recombinant DNA
    SentencesResources
    Briefly, the transfection reaction consisted of 1mg of purified, cGMP sourced plasmid DNA (Aldevron, pCoV 1B-06-PL) plus 3mL of Turbo 293 Transfection Reagent (Speed Biosystems, Cat No. PXX1001) mixed in 1X PBS per liter of transfected cells.
    pCoV 1B-06-PL
    suggested: None
    SARS-CoV-1 and SARS-CoV-2 pseudovirus neutralization assay: Pseudovirions were produced by co-transfection of HEK293T/17 cells with either the SARS-CoV-1 (Sino 1-11, GenBank # AY485277) or SARS-CoV-2 (WA1/2020 GenBank # MT246667) S expression plasmid and an HIV-1 pNL4-3 luciferase reporter plasmid (pNL4-3.Luc.R-E-, NIH AIDS Reagent Program).
    pNL4-3
    suggested: None
    pNL4-3.Luc.R-E-
    suggested: None
    Software and Algorithms
    SentencesResources
    The design, production, stability, and initial characterization of SpFN adjuvanted with ALFQ has been described previously 20.
    ALFQ
    suggested: (aLFQ, RRID:SCR_005925)
    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
    Statistical Analysis: All statistical analysis were performed using GraphPad Prism version 8 software.
    GraphPad Prism
    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
    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.

  2. Version published to 10.1101/2021.06.16.448525v1 on bioRxiv