NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge

  1. Mimi Guebre-Xabier
  2. Nita Patel
  3. Jing-Hui Tian
  4. Bin Zhou
  5. Sonia Maciejewski
  6. Kristal Lam
  7. Alyse D. Portnoff
  8. Michael J. Massare
  9. Matthew B. Frieman
  10. Pedro A. Piedra
  11. Larry Ellingsworth
  12. Gregory Glenn
  13. Gale Smith

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Abstract

There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques ( Macaca fascicularis ) immunized with NVX-CoV2373 and the saponin-based Matrix-M adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine ( NCT04368988 ).

Highlights

  • Full-length SARS-CoV-2 prefusion spike with Matrix-M1™ (NVX-CoV2373) vaccine.

  • Induced hACE2 receptor blocking and neutralizing antibodies in macaques.

  • Vaccine protected against SARS-CoV-2 replication in the nose and lungs.

  • Absence of pulmonary pathology in NVX-CoV2373 vaccinated macaques.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.18.256578: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Animal ethics: The in-life portion of the study was conducted at BIOQUAL, Inc (Rockville, MD).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableFemale and male, > 3 years old at study initiation, cynomolgus macaques (Macaca fascicularis) were obtained from Primgen, Inc (Hines, IL) and maintained at BIOQUAL, Inc for the entire in-life portion of the study.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Sera were analyzed for anti-SARS-CoV-2 S IgG, hACE2 receptor inhibition, and virus neutralizing antibody titers. 2.9. Histopathology: Animals were euthanized 7-days following SARS-CoV-2 challenge (Day 42) and lung tissues collected.
    anti-SARS-CoV-2 S IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 generated from isolate 2019-nCoV/USA-WA1/2020 was received from BEI Resources (NR-52281; lot # 70033175) and expanded in Vero E6 cells for challenge stock generation.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Individual animal hACE2 receptor inhibiting titers, mean titers, and SEM were plotted using GraphPad Prism 7.05 software.
    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
    NCT04368988Active, not recruitingEvaluation of the Safety and Immunogenicity of a SARS-CoV-2 …

    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.

    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 10.1101/2020.08.18.256578 on bioRxiv