Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

  1. Simon P. Graham
  2. Rebecca K. McLean
  3. Alexandra J. Spencer
  4. Sandra Belij-Rammerstorfer
  5. Daniel Wright
  6. Marta Ulaszewska
  7. Jane C. Edwards
  8. Jack W. P. Hayes
  9. Veronica Martini
  10. Nazia Thakur
  11. Carina Conceicao
  12. Isabelle Dietrich
  13. Holly Shelton
  14. Ryan Waters
  15. Anna Ludi
  16. Ginette Wilsden
  17. Clare Browning
  18. Dagmara Bialy
  19. Sushant Bhat
  20. Phoebe Stevenson-Leggett
  21. Philippa Hollinghurst
  22. Ciaran Gilbride
  23. David Pulido
  24. Katy Moffat
  25. Hannah Sharpe
  26. Elizabeth Allen
  27. Valerie Mioulet
  28. Chris Chiu
  29. Joseph Newman
  30. Amin S. Asfor
  31. Alison Burman
  32. Sylvia Crossley
  33. Jiandong Huo
  34. Raymond J. Owens
  35. Miles Carroll
  36. John A. Hammond
  37. Elma Tchilian
  38. Dalan Bailey
  39. Bryan Charleston
  40. Sarah C. Gilbert
  41. Tobias J. Tuthill
  42. Teresa Lambe

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Abstract

Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.20.159715: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Ethics statement: Mouse and pig studies were performed in accordance with the UK Animals (Scientific Procedures) Act 1986 and with approval from the relevant local Animal Welfare and Ethical Review Body (Mice – Project License P9808B4F1, and pigs – Project License PP1804248).
    Randomizationnot detected.
    BlindingResearchers performing the VNTs were blinded to the identity of the samples.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 isolate England-2 stocks were grown in Vero E6 cells using a multiplicity of infection (MOI) of 0.0001 for 3 days at 37 °C in propagation media (maintenance media containing 2% FBS).
    Vero E6
    suggested: None
    Pseudovirus neutralisation test (pVNT): Lentiviral-based SARS-CoV-2 pseudoviruses were generated in HEK293T cells incubated at 37 °C, 5% CO2.
    HEK293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Assessment of SARS-CoV-2 Specific T cell Responses: Data Analysis: GraphPad Prism 8.1.2 (GraphPad Software, San Diego, USA) was used for graphical and statistical analysis of data sets.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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
    NCT04324606Active, not recruitingA Study of a Candidate COVID-19 Vaccine (COV001)
    NCT04400838RecruitingInvestigating a Vaccine Against COVID-19

    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 10.1038/s41541-020-00221-3
  3. ScreenIT

    SciScore for 10.1101/2020.06.20.159715: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementMethods Ethics statement Mouse and pig studies were performed in accordance with the UK Animals ( Scientific Procedures ) Act 1986 and with approval from the relevant local Animal Welfare and Ethical Review Body ( Mice - Project License P9808B4F1 , and pigs - Project License PP1804248) .RandomizationImmunogenicity trials Mice: Inbred female BALB/cOlaHsd ( BALB/c ) ( Envigo ) and outbred Crl:CD1 ( CD1 ) ( Charles River ) of at least 6 weeks of age were randomly allocated into ‘prime-only’ or ‘prime-boost’ vaccination groups ( BALB/c n=5 and CD1 n=8) .BlindingResearchers performing the VNTs were blinded to the identity of the samples .Power Analysisnot detected.Sex as a biological variableImmunogenicity trials Mice: Inbred female BALB/cOlaHsd ( BALB/c ) ( Envigo ) and outbred Crl:CD1 ( CD1 ) ( Charles River ) of at least 6 weeks of age were randomly allocated into ‘prime-only’ or ‘prime-boost’ vaccination groups ( BALB/c n=5 and CD1 n=8) .Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Following washing , bound antibodies were detected by addition of alkaline phosphatase-conjugated goat anti-mouse IgG ( Sigma-Aldrich) , diluted 1/5000 in casein , for 1 hour at RT and detection of anti-mouse IgG by the addition of pNPP substrate ( Sigma-Aldrich) .
    anti-mouse IgG
    suggested: None
    SARS-CoV-2 RBD and FL-S specific antibodies in serum were assessed as detailed previously26 with the exception of the following two steps .
    FL-S
    suggested: None
    The conjugated secondary antibody was replaced with goat anti-porcine IgG HRP ( Abcam , Cambridge , UK ) at 1/10,000 dilution in PBS with 0.1 % Tween20 and 1 % non-fat milk .
    anti-porcine IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 stocks were titrated on Vero E6 cells using MEM ( Gibco) , 2 % FCS ( Labtech , Heathfield , UK) , 0.8 % Avicel ( FMC BioPolymer , Girvan , UK ) as overlay .
    Vero E6
    suggested: CVCL_XD71
    Target HEK293T cells , previously transfected with 500 ng of a human ACE2 expression plasmid ( Addgene , Cambridge , MA , USA ) were seeded at a density of 2 × 104 in 100 µL DMEM-10 % in a white flat-bottomed 96-well plate one day prior to harvesting of SARS-CoV-2 pps .
    HEK293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Cells were analysed using a BD LSRFortessa flow cytometer and FlowJo X software.
    FlowJo
    suggested: (FlowJo, SCR_008520)
    (GraphPad Software, San Diego, USA) was used for graphical and statistical analysis of data sets.
    GraphPad
    suggested: (GraphPad Prism, SCR_002798)

    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 OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.06.20.159715v1 on bioRxiv