Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants

  1. Daniel Junker
  2. Matthias Becker
  3. Teresa R Wagner
  4. Philipp D Kaiser
  5. Sandra Maier
  6. Tanja M Grimm
  7. Johanna Griesbaum
  8. Patrick Marsall
  9. Jens Gruber
  10. Bjoern Traenkle
  11. Constanze Heinzel
  12. Yudi T Pinilla
  13. Jana Held
  14. Rolf Fendel
  15. Andrea Kreidenweiss
  16. Annika Nelde
  17. Yacine Maringer
  18. Sarah Schroeder
  19. Juliane S Walz
  20. Karina Althaus
  21. Gunalp Uzun
  22. Marco Mikus
  23. Tamam Bakchoul
  24. Katja Schenke-Layland
  25. Stefanie Bunk
  26. Helene Haeberle
  27. Siri Göpel
  28. Michael Bitzer
  29. Hanna Renk
  30. Jonathan Remppis
  31. Corinna Engel
  32. Axel R Franz
  33. Manuela Harries
  34. Barbora Kessel
  35. Berit Lange
  36. Monika Strengert
  37. Gerard Krause
  38. Anne Zeck
  39. Ulrich Rothbauer
  40. Alex Dulovic
  41. Nicole Schneiderhan-Marra

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Abstract

Background

The rapid emergence of the Omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the World Health Organization. Subsequently, Omicron evolved into distinct sublineages (eg, BA.1 and BA.2), which currently represent the majority of global infections. Initial studies of the neutralizing response toward BA.1 in convalescent and vaccinated individuals showed a substantial reduction.

Methods

We assessed antibody (immunoglobulin G [IgG]) binding, ACE2 (angiotensin-converting enzyme 2) binding inhibition, and IgG binding dynamics for the Omicron BA.1 and BA.2 variants compared to a panel of VOCs/variants of interest, in a large cohort (N = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals.

Results

While Omicron was capable of efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to wild type. Whereas BA.1 exhibited less IgG binding compared to BA.2, BA.2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to Omicron only improved after administration of a third dose.

Conclusions

Omicron BA.1 and BA.2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind to Omicron. The extent of the mutations within both variants prevents a strong inhibitory binding response. As a result, both Omicron variants are able to evade control by preexisting antibodies.

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  1. Version published to 10.1093/cid/ciac498
  2. ScreenIT

    SciScore for 10.1101/2021.12.30.21267519: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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.

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  3. Version published to 10.1101/2021.12.30.21267519v1 on medRxiv