SARS-CoV-2 501Y.V2 (B.1.351) elicits cross-reactive neutralizing antibodies

  1. Thandeka Moyo-Gwete
  2. Mashudu Madzivhandila
  3. Zanele Makhado
  4. Frances Ayres
  5. Donald Mhlanga
  6. Brent Oosthuysen
  7. Bronwen E. Lambson
  8. Prudence Kgagudi
  9. Houriiyah Tegally
  10. Arash Iranzadeh
  11. Deelan Doolabh
  12. Lynn Tyers
  13. Lionel R. Chinhoyi
  14. Mathilda Mennen
  15. Sango Skelem
  16. Gert Marais
  17. Constantinos Kurt Wibmer
  18. Jinal N Bhiman
  19. Veronica Ueckermann
  20. Theresa Rossouw
  21. Michael Boswell
  22. Tulio de Oliveira
  23. Carolyn Williamson
  24. Wendy A Burgers
  25. Ntobeko Ntusi
  26. Lynn Morris
  27. Penny L Moore

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Abstract

Neutralization escape by SARS-CoV-2 variants, as has been observed in the 501Y.V2 (B.1.351) variant, has impacted the efficacy of first generation COVID-19 vaccines. Here, the antibody response to the 501Y.V2 variant was examined in a cohort of patients hospitalized with COVID-19 in early 2021 - when over 90% of infections in South Africa were attributed to 501Y.V2. Robust binding and neutralizing antibody titers to the 501Y.V2 variant were detected and these binding antibodies showed high levels of cross-reactivity for the original variant, from the first wave. In contrast to an earlier study where sera from individuals infected with the original variant showed dramatically reduced potency against 501Y.V2, sera from 501Y.V2-infected patients maintained good cross-reactivity against viruses from the first wave. Furthermore, sera from 501Y.V2-infected patients also neutralized the 501Y.V3 (P.1) variant first described in Brazil, and now circulating globally. Collectively these data suggest that the antibody response in patients infected with 501Y.V2 has a broad specificity and that vaccines designed with the 501Y.V2 sequence may elicit more cross-reactive responses.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.06.434193: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study received ethics approval from the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (R021/2020).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Expression and purification of SARS-CoV-2 antigens: SARS-CoV-2 spike and SBD (RBD + subdomain 1) proteins were expressed in Human Embryonic Kidney (HEK) 293F suspension cells by transfecting the cells with SARS CoV-2 plasmid DNA.
    HEK
    suggested: RRID:CVCL_6642)
    : SARS-CoV-2 pseudotyped lentiviruses were prepared by co-transfecting the HEK 293T cell line with either the SARS-CoV-2 614G spike (D614G), SARS-CoV2 501Y.V2-RBD spike (K417N, E484K and N501Y, D614G) or SARS-CoV-2 501Y.V2 spike (L18F, D80A, D215G, K417N, E484K, N501Y, D614G, A701V, 242-244 del) and the SARS-CoV-2 501Y.V3 spike (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F) plasmids in conjunction with a firefly luciferase encoding lentivirus backbone plasmid and a murine leukemia virus backbone plasmid.
    HEK 293T
    suggested: None
    Software and Algorithms
    SentencesResources
    Mutations were confirmed visually with bam files using Geneious software (Biomatters Ltd, New Zealand).
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    The pipeline contains several python scripts that manage the analysis workflow.
    python
    suggested: (IPython, RRID:SCR_001658)
    It performs alignment of genomes in MAFFT (Katoh and Standley, 2013), phylogenetic tree inference in IQ-Tree V1.6.9 (Nguyen et al., 2015), tree dating and ancestral state construction and annotation (https://github.com/nextstrain/ncov).
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    IQ-Tree
    suggested: (IQ-TREE, RRID:SCR_017254)
    : SARS-CoV-2 pseudotyped lentiviruses were prepared by co-transfecting the HEK 293T cell line with either the SARS-CoV-2 614G spike (D614G), SARS-CoV2 501Y.V2-RBD spike (K417N, E484K and N501Y, D614G) or SARS-CoV-2 501Y.V2 spike (L18F, D80A, D215G, K417N, E484K, N501Y, D614G, A701V, 242-244 del) and the SARS-CoV-2 501Y.V3 spike (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F) plasmids in conjunction with a firefly luciferase encoding lentivirus backbone plasmid and a murine leukemia virus backbone plasmid.
    SARS-CoV-2
    suggested: (Active Motif Cat# 91351, RRID:AB_2847848)

    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: We detected the following sentences addressing limitations in the study:
    One limitation of our study is the absence of matched SARS-CoV-2 spike sequence data for all participants. However, of the 28 samples that were sequenced, all were 501Y.V2. The fact that similar findings were seen in the subset of those who were sequenced, also supports our conclusions (Tegally et al., 2021). This together with the finding that 501Y.V2 accounted almost all of the infections in South Africa, confirms the high probability that most infections in this cohort were caused by 501Y.V2. Furthermore, we have ruled out prior symptomatic infection by the original variant in all but 2 individuals. Although we cannot rule out prior asymptomatic infection, the high number of samples tested makes the probability of a substantial proportion of these being re-infections unlikely. Overall, the emergence of variants with increased resistance to neutralizing antibodies has major implications for vaccine design. However, 501Y.V2 appears to generate a robust antibody response in hospitalized individuals. Our data indicate that vaccines built upon the spike protein of 501Y.V2 may be promising candidates for the elicitation of cross-reactive neutralizing antibodies to SARS-CoV-2.

    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.

    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 10.1101/2021.03.06.434193v2 on bioRxiv
  3. Version published to 10.1101/2021.03.06.434193v1 on bioRxiv