Human serum from SARS-CoV-2-vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant

  1. Maren Schubert
  2. Federico Bertoglio
  3. Stephan Steinke
  4. Philip Alexander Heine
  5. Mario Alberto Ynga-Durand
  6. Henrike Maass
  7. Josè Camilla Sammartino
  8. Irene Cassaniti
  9. Fanglei Zuo
  10. Likun Du
  11. Janin Korn
  12. Marko Milošević
  13. Esther Veronika Wenzel
  14. Fran Krstanović
  15. Saskia Polten
  16. Marina Pribanić-Matešić
  17. Ilija Brizić
  18. Fausto Baldanti
  19. Lennart Hammarström
  20. Stefan Dübel
  21. Alan Šustić
  22. Harold Marcotte
  23. Monika Strengert
  24. Alen Protić
  25. Antonio Piralla
  26. Qiang Pan-Hammarström
  27. Luka Čičin-Šain
  28. Michael Hust

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Abstract

Background

The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants.

Methods

All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed.

Results

Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup.

Conclusion

These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.

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  1. Version published to 10.1186/s12916-022-02312-5
  2. ScreenIT

    SciScore for 10.1101/2021.12.10.21267523: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: While all voluntary donors were informed about the project and gave their consent for the study, consent requirement was waived by the ethical committee in Rijeka for patients in intensive care where sampling was a part of routine diagnostics.
    IRB: While all voluntary donors were informed about the project and gave their consent for the study, consent requirement was waived by the ethical committee in Rijeka for patients in intensive care where sampling was a part of routine diagnostics.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    Expression and purification of ACE2-hFc: The extracellular domain of ACE2 receptor (GenBank NM_021804.3) was produced in pCSE2.6-hFc expression vector in Expi293F cells (Thermo Fisher Scientific) as described before (Bertoglio et al., 2021b).
    pCSE2.6-hFc
    suggested: None
    Software and Algorithms
    SentencesResources
    EC50 were calculated with OriginPro Version 9.1, fitting to a five-parameter logistic curve.
    OriginPro
    suggested: None
    OD450 nm-620 nm was measured in an ELISA plate reader (BioTek Instruments, Epoch) and its software Gen5 version 3.03 was used to calculate EC50 values, further expressed as relative potency towards an internal calibrant for which the Binding Antibody Unit (BAU) was calculated using the WHO International Standard 20/136 in relation to the original Wuhan strain RBD.
    Gen5
    suggested: (Gen5, RRID:SCR_017317)
    The graphics were created by GraphPad Prism 9.1.
    GraphPad Prism
    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.
    • No funding statement was detected.
    • 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.

  3. Version published to 10.1101/2021.12.10.21267523 on medRxiv