Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing

  1. Joan E.M. van der Lubbe
  2. Sietske K. Rosendahl Huber
  3. Aneesh Vijayan
  4. Liesbeth Dekking
  5. Ella van Huizen
  6. Jessica Vreugdenhil
  7. Ying Choi
  8. Miranda R.M. Baert
  9. Karin Feddes-de Boer
  10. Ana Izquierdo Gil
  11. Marjolein van Heerden
  12. Tim J. Dalebout
  13. Sebenzile K. Myeni
  14. Marjolein Kikkert
  15. Eric J. Snijder
  16. Leon de Waal
  17. Koert J. Stittelaar
  18. Jeroen T.B.M. Tolboom
  19. Jan Serroyen
  20. Leacky Muchene
  21. Leslie van der Fits
  22. Lucy Rutten
  23. Johannes P.M. Langedijk
  24. Dan H. Barouch
  25. Hanneke Schuitemaker
  26. Roland C. Zahn
  27. Frank Wegmann

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Abstract

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1×10 9 vp and 1×10 10 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.08.425915: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Paraffin sections of lung, trachea and nose sections of all animals were automatically stained (Ventana Discovery Ultra, Roche, France), using rabbit polyclonal anti-SARS-CoV Nucleocapsid protein antibody (NP, Novus NB100-56576, 1/300) which is cross reactive towards SARS-CoV-2 NP.
    anti-SARS-CoV Nucleocapsid protein
    suggested: (Creative Diagnostics Cat# DMAB8869, RRID:AB_2392503)
    NP
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    To this end, serial dilutions of the samples (throat swabs, and tissue homogenates) were made and incubated on Vero E6 monolayers for 1 hour at 37 °C.
    Vero E6
    suggested: None
    Vero-E6 cells were seeded at 12,000 cells/well in 96-well tissue culture plates 1 day prior to infection.
    Vero-E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc. Cary, NC, US) and R version 3.6.1 (2019-07-05).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    From the binding and neutralizing antibody data pooled from different regimens and dose levels of Ad26.COV2.S, logistic regression models were built with Firth’s correction49, with protection outcome as the dependent variable, and the wtVNA and Log10 transformed ELISA data before inoculation as the independent variable.
    Firth’s
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    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
    NCT04505722Active, not recruitingA Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Medi…
    NCT04614948RecruitingA Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-medi…

    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

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  2. Version published to 10.1101/2021.01.08.425915v1 on bioRxiv