Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern

  1. Dale Kitchin
  2. Simone I. Richardson
  3. Mieke A. van der Mescht
  4. Thopisang Motlou
  5. Nonkululeko Mzindle
  6. Thandeka Moyo-Gwete
  7. Zanele Makhado
  8. Frances Ayres
  9. Nelia P. Manamela
  10. Holly Spencer
  11. Bronwen Lambson
  12. Brent Oosthuysen
  13. Haajira Kaldine
  14. Marizane du Pisanie
  15. Mathilda Mennen
  16. Sango Skelem
  17. Noleen Williams
  18. Ntobeko A.B. Ntusi
  19. Wendy A. Burgers
  20. Glenda G. Gray
  21. Linda-Gail Bekker
  22. Michael T. Boswell
  23. Theresa M. Rossouw
  24. Veronica Ueckermann
  25. Penny L. Moore

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Abstract

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  1. Version published to 10.1016/j.xcrm.2022.100535
  2. Version published to 10.1101/2021.11.08.21266049v3 on medRxiv
  3. Version published to 10.1101/2021.11.08.21266049v2 on medRxiv
  4. ScreenIT

    SciScore for 10.1101/2021.11.08.21266049: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics approval was obtained from the Human Research Ethics Committees of the University of the Witwatersrand (ethics reference number: M210465), University of Pretoria (ethics reference number: 247/2020) and University of Cape Town (ethics reference numbers: 190/2020 and 209/2020).
    Consent: Written informed consent was obtained from all participants.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Monoclonal antibodies CB6 and CA1 were used as positive controls.
    CA1
    suggested: None
    Antibody-dependent cellular cytotoxicity (ADCC) assay: The ability of plasma antibodies to cross-link spike expressing cells and signal through FcγRIIIa (CD16) was measured as a proxy for ADCC.
    CD16
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 antigens: For ELISA, SARS-CoV-2 original variant (D614G) full spike proteins were expressed in Human Embryonic Kidney (HEK) 293F suspension cells by transfecting the cells with the respective expression plasmid.
    HEK
    suggested: RRID:CVCL_6642)
    Briefly, 293T/17 cells (HEK293T cell line) were co-transfected with a SARS-CoV-2 spike plasmid in conjunction with a firefly luciferase encoding lentivirus backbone plasmid (pNL4-3.
    293T/17
    suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)
    HEK293T
    suggested: None
    Jurkat-Lucia™ NFAT-CD16 cells (Invivogen) (2×105 cells/well) were added and incubated for 24 hours at 37°C, 5% CO2.
    NFAT-CD16
    suggested: RRID:CVCL_A7ZT)
    Recombinant DNA
    SentencesResources
    Spike plasmid and lentiviral pseudovirus production: The SARS-CoV-2 Wuhan-1 spike gene sequence, cloned into pcDNA3.1, was mutated using the QuikChange Lightning Site-Directed Mutagenesis kit (Agilent Technologies) and NEBuilder HiFi DNA Assembly Master Mix (New England Biosciences) to include D614G (ancestrall) or lineage defining mutations for Beta (L18F, D80A, D215G, Δ242-244, K417N, E484K, N501Y, D614G and A701V), Gamma (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F), Delta (T19R, Δ156-157, R158G, L452R, T478K, D614G, P681R, D950N), C1.2. (P9L, C136F, Δ144, R190S, D215G, Δ242-243, Y449H, E484K, N501Y, D614G, H655Y, N679K, T716I, T859N) and A.VOI.V2 (D80Y, Δ144, I210N, Δ211, D215G, R246M, Δ247-249, W258L, R346K, T478R, E484K, H655Y, P681H, Q957H).
    pcDNA3.1
    suggested: RRID:Addgene_79663)
    Briefly, 293T/17 cells (HEK293T cell line) were co-transfected with a SARS-CoV-2 spike plasmid in conjunction with a firefly luciferase encoding lentivirus backbone plasmid (pNL4-3.
    pNL4-3
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Analyses were performed in Prism (v9; GraphPad Software Inc, San Diego, CA, USA).
    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: No clinical trial numbers were referenced.

    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.

  5. Version published to 10.1101/2021.11.08.21266049v1 on medRxiv