Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

  1. Chris Davis
  2. Nicola Logan
  3. Grace Tyson
  4. Richard Orton
  5. William T. Harvey
  6. Jonathan S. Perkins
  7. Guy Mollett
  8. Rachel M. Blacow
  9. The COVID-19 Genomics UK (COG-UK) Consortium
  10. Thomas P. Peacock
  11. Wendy S. Barclay
  12. Peter Cherepanov
  13. Massimo Palmarini
  14. Pablo R. Murcia
  15. Arvind H. Patel
  16. David L. Robertson
  17. John Haughney
  18. Emma C. Thomson
  19. Brian J. Willett
  20. on behalf of the COVID-19 DeplOyed VaccinE (DOVE) Cohort Study investigators

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Abstract

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11 - fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

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  1. Version published to 10.1371/journal.ppat.1010022
  2. ScreenIT

    SciScore for 10.1101/2021.06.23.21259327: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Ethics: all participants gave informed consent to take part in the study.
    IRB: The study was approved by the North-West Liverpool Central Research Ethics Committee (REC reference 21/NW/0073).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    ELISA for SARS-CoV-2 antibodies: ELISAs for SARS-CoV-2 antibodies were performed as described previously 17.
    SARS-CoV-2
    suggested: None
    Measurement of neutralising antibody activity using viral pseudotypes: HEK293, HEK293T, and 293-ACE2 cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% foetal bovine serum, 200mM L-glutamine, 100µg/ml streptomycin and 100 IU/ml penicillin.
    HEK293
    suggested: (Creative Biomart Cat# APOA5-26876TH, RRID:AB_2532021)
    Experimental Models: Cell Lines
    SentencesResources
    Measurement of neutralising antibody activity using viral pseudotypes: HEK293, HEK293T, and 293-ACE2 cells were maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% foetal bovine serum, 200mM L-glutamine, 100µg/ml streptomycin and 100 IU/ml penicillin.
    HEK293
    suggested: None
    HEK293T
    suggested: None
    293-ACE2
    suggested: RRID:CVCL_DR94)
    Recombinant DNA
    SentencesResources
    Briefly, the SARS-CoV-2 RBD and S1 constructs, spanning SARS-CoV-2 S (UniProt ID P59594) residues 319-541 (RVQPT…KCVNF) and 1-530 (MFVFL…GPKKS), respectively, were produced with C-terminal twin Strep tags in the mammalian expression vector pQ-3C-2xStrep38.
    pQ-3C-2xStrep38
    suggested: None
    HEK293T cells were transfected with the appropriate SARS-CoV-2 S gene expression vector (wild type or variant) in conjunction with p8.91 18 and pCSFLW 19 using polyethylenimine (PEI, Polysciences, Warrington, USA).
    pCSFLW 19
    suggested: None
    The S gene of B.1.351 (South Africa) was based on the codon-optimised sequence of the Wuhan-Hu-1 expression construct, synthesised by Genscript (Netherlands) and sub-cloned into the pCDNA6 expression vector.
    pCDNA6
    suggested: RRID:Addgene_134280)

    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

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  3. Version published to 10.1101/2021.06.23.21259327v1 on medRxiv