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BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced

Xinyue Chang, Gilles Sousa Augusto, Xuelan Liu, Thomas M Kündig, Monique Vogel, View ORCID ProfileMona O. Mohsen, Martin F. Bachmann
doi: https://doi.org/10.1101/2021.03.13.435222
Xinyue Chang
1Department of Immunology, University clinic of Rheumatology and Immunology, Inselspital, Bern, Switzerland
2Department of BioMedical Research, University of Bern, Bern, Switzerland
MSc
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Gilles Sousa Augusto
1Department of Immunology, University clinic of Rheumatology and Immunology, Inselspital, Bern, Switzerland
2Department of BioMedical Research, University of Bern, Bern, Switzerland
5Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), The Jenner Institute, University of Oxford, Oxford, UK
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Xuelan Liu
1Department of Immunology, University clinic of Rheumatology and Immunology, Inselspital, Bern, Switzerland
3International Immunology Centre, Anhui Agricultural University, Hefei, China
MSc
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Thomas M Kündig
4Dermatology University, Hospital Zürich, Zürich, Switzerland
MD
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Monique Vogel
1Department of Immunology, University clinic of Rheumatology and Immunology, Inselspital, Bern, Switzerland
2Department of BioMedical Research, University of Bern, Bern, Switzerland
PhD
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Mona O. Mohsen
1Department of Immunology, University clinic of Rheumatology and Immunology, Inselspital, Bern, Switzerland
2Department of BioMedical Research, University of Bern, Bern, Switzerland
PhD
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  • ORCID record for Mona O. Mohsen
  • For correspondence: martin.bachmann@dbmr.unibe.ch mona.mohsen@dbmr.unibe.ch
Martin F. Bachmann
1Department of Immunology, University clinic of Rheumatology and Immunology, Inselspital, Bern, Switzerland
2Department of BioMedical Research, University of Bern, Bern, Switzerland
3International Immunology Centre, Anhui Agricultural University, Hefei, China
5Nuffield Department of Medicine, Centre for Cellular and Molecular Physiology (CCMP), The Jenner Institute, University of Oxford, Oxford, UK
PhD
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  • For correspondence: martin.bachmann@dbmr.unibe.ch mona.mohsen@dbmr.unibe.ch
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Abstract

Background Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein.

Objective We aimed to assess how mutations in RBD affected recognition of immune sera by antibodies induced by natural infection versus immunization with BNT162b2, a mRNA-based vaccine against COVID-19.

Methods We produced SARS-CoV-2 RBD mutants with single mutations in the receptor binding domain (RBD) region (E484K, K417N, N501Y) or with all 3 mutations combined, as occurring in the newly emerged variants B.1.351 (South Africa) and P.1 (Brazil). Using standard and avidity ELISAs, we determined the binding capacities to mutant RBDs of antibodies induced by infection versus vaccination.

Results These binding assays showed that vaccination induced antibodies recognize both wildtype and mutant RBDs with higher avidities than those raised by infection. Nevertheless, recognition of mutants RBDK417N and RBDN501Y was 2.5-3-fold reduced while RBDE484K and the triple mutant were 10-fold less well recognized, demonstrating that the mutation at position 484 was key for the observed loss in cross-reactivity.

Conclusion Our binding data demonstrate improved recognition of mutant viruses by BNT162b2-induced antibodies compared to those induced by natural infection. Recognition may, however, be 10-fold reduced for the variants B.1.351/P.1, suggesting that the development of a new vaccine is warranted. The E484K mutation is an key hurdle for immune recognition, convalescent plasma and monoclonal antibody therapy as well as serological assays based on the wildtype sequence may therefore seriously impaired.

Capsule summary BNT162b2 mRNA COVID-19 vaccine-induced antibodies recognize mutant viruses with up to 10-fold lower efficiency

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding The work was supported by Saiba AG and the Swiss National Science Foundation (SNF grants 31003A 149925 and 310030-179459).

  • Conflict of interests M. F. Bachmann is a board member of Saiba AG, involved in the development of RBD-CuMV a vaccine against COVID-19. All other authors declare no conflict of interest.

  • Abbreviations

    SARS-CoV-2
    Severe Acute Respiratory Syndrome Coronavirus type 2
    RBD
    Receptor Binding Domain
    ACE2
    Angiotensin-Converting Enzyme 2
    RBD
    Receptor Binding Domain
    RBM
    Receptor Binding Motif
    COVID-19
    Coronavirus disease 2019
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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    BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced
    Xinyue Chang, Gilles Sousa Augusto, Xuelan Liu, Thomas M Kündig, Monique Vogel, Mona O. Mohsen, Martin F. Bachmann
    bioRxiv 2021.03.13.435222; doi: https://doi.org/10.1101/2021.03.13.435222
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    BNT162b2 mRNA COVID-19 vaccine induces antibodies of broader cross-reactivity than natural infection but recognition of mutant viruses is up to 10-fold reduced
    Xinyue Chang, Gilles Sousa Augusto, Xuelan Liu, Thomas M Kündig, Monique Vogel, Mona O. Mohsen, Martin F. Bachmann
    bioRxiv 2021.03.13.435222; doi: https://doi.org/10.1101/2021.03.13.435222

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