Cross reactivity of spike glycoprotein induced antibody against Delta and Omicron variants before and after third SARS-CoV-2 vaccine dose

  1. Sian E Faustini
  2. Adrian M Shields
  3. Gemma Banham
  4. Nadezhda Wall
  5. Saly Al-Taei
  6. Chloe Tanner
  7. Zahra Ahmed
  8. Elena Efstathiou
  9. Neal Townsend
  10. Tim Plant
  11. Marisol Perez-Toledo
  12. Aleksandra Jasiulewicz
  13. Ruth Price
  14. James McLaughlin
  15. John Farnan
  16. Julie Moore
  17. Louise Robertson
  18. Andrew Nesbit
  19. Grace Curry
  20. Amy Black
  21. Adam F Cunningham
  22. Lorraine Harper
  23. Tara Moore
  24. Mark T Drayson
  25. Alex G Richter

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Abstract

Variants of SARS-CoV-2 may evade natural and vaccine induced immunity and monoclonal antibody immunotherapeutics. There is an urgent need to know how well antibodies, induced by healthy and Clinically Extremely Vulnerable (CEV) patients, will bind and thus help reduce transmission and severity of infection from variants of concern (VOC). This study determines the cross-reactive binding of serum antibodies obtained prior to and 28 days after a third vaccination in three cohorts; a health care worker cohort who received three doses of Pfizer-BioNtech (PPP), a cohort of CEV patients received two doses of the AstraZeneca-ChAdOx1-nCoV-19 (AAP) vaccine, followed by a third PFZ vaccine and a haemodialysis cohort that had a mixture of two AZ or PFZ vaccines followed by a PFZ booster. Six months post second vaccine there was evidence of antibody waning with 58.9% of individuals in the HD cohort seropositive against Wuhan, 34.4% Delta and 62.2% Omicron strains. For the AAP cohort, equivalent figures were 62.5%, 45.8% and 91.7% and the PPP cohort 92.2%, 90% and 91.1%. Post third dose vaccination there were universal increases in seropositivity and median optical density. For the HD cohort, 98.8% were seropositive to the Wuhan strain, 97.6% against Delta and 100% against Omicron strains. For the PPP and AAP cohorts, 100% were seropositive against all 3 strains. Lastly, we examined the WHO NIBSC 20/136 standard and there was no loss of antibody binding to either VOC. Similarly, a dilution series of Sotrovimab (GSK) found this therapeutic monoclonal antibody bound similarly to all VOC.

Highlights

  • IgG anti-SARS-CoV-2 Omicron spike glycoprotein antibody levels were high in 100% of health care workers (HCW), a general practice population considered clinically extremely vulnerable (CEV) and haemodialysis patients (HD) 4 weeks after a third SARS-CoV-2 vaccine dose (Pfizer-BioNtech-PFZ).

  • For both Delta and Omicron variant spike glycoproteins these antibody levels were highest in the CEV cohort who had previously received two doses of AstraZeneca ChAdOx1 nCoV-19 vaccine (AAP), lower in HCW who had previously received two doses of PFZ (PPP) and lowest in HD who had a mix of vaccines for the first and second dose

  • Prior to this third vaccine dose and 6 months post second vaccine dose there was evidence of significant waning of antibodies against VOC.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.30.21268308: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethical approval: The COCO study was ethically approved for this work by the London - Camden and Kings Cross Research Ethics Committee on behalf of the United Kingdom Health Research Authority – reference 20/HRA/1817.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    ELISAs: Here we have used the core design of an anti-IgG/A/M SARS-CoV-2 ELISA (10,11) to measure IgG antibodies specific for spike protein from the original Wuhan strain (Abingdon Health, York Biotech Campus Sand Hutton, York) (12), B.1.617.2 (Delta -Abingdon Health) and B.1.1.529 (Omicron - SinoBiological China).
    anti-IgG/A/M SARS-CoV-2 ELISA
    suggested: None
    measure IgG
    suggested: None
    HRP-conjugated mouse-anti-human R10-IgG (monoclonal antibody obtained from Dr. Margaret Goodall, Clinical Immunology Service, University of Birmingham) (1:8000 dilution) was then added to the plate and incubated for 1 hour at RT.
    HRP-conjugated mouse-anti-human R10-IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Firstly a health care worker cohort from University Hospitals Birmingham from the Determining the immune response to SARS-CoV-2 infection in convalescent health care workers (COCO) study (7,8), who received three doses of PFZ.
    COCO
    suggested: (CoCo, RRID:SCR_010947)
    Statistics: All analyses were undertaken on GraphPad Prism 9 (San Diego, California).
    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.

  2. Version published to 10.1101/2021.12.30.21268308v1 on medRxiv