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Article

Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron

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Department of BioMedical Research, University of Bern, 3010 Bern, Switzerland
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Department of Immunology RI, University Hospital Bern, 3010 Bern, Switzerland
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The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
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Department of Viroscience, Erasmus Medical Center, 3015 Rotterdam, The Netherlands
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Artemis Bio-Support, 2629 Delft, The Netherlands
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Biomedical Research Complex, Qatar University, Doha P.O. Box 2713, Qatar
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Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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Saiba GmbH, 8808 Pfaeffikon, Switzerland
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Authors to whom correspondence should be addressed.
Academic Editors: Emanuele Montomoli, Serena Marchi and Claudia Maria Trombetta
Vaccines 2022, 10(5), 743; https://doi.org/10.3390/vaccines10050743
Received: 4 April 2022 / Revised: 5 May 2022 / Accepted: 6 May 2022 / Published: 9 May 2022
(This article belongs to the Special Issue SARS-CoV-2 Variants Research and Ending the COVID-19 Pandemic)
In this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by physio-chemical characterization of this variant in comparison to the wild-type Wuhan and the Delta variant (B.1.617.2). Convalescent sera, as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna-mRNA-1273® or Pfizer-BNT162b2®), were used for comparison in this study. Our data demonstrate that both Delta, as well as Omicron variants, exhibit a higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to the reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not the Delta variant escaped antibody recognition, most likely because only Omicron exhibits the mutation at E484A, a position associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA-based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape. View Full-Text
Keywords: Omicron; Delta; SARS-CoV-2; antibody Omicron; Delta; SARS-CoV-2; antibody
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MDPI and ACS Style

Vogt, A.-C.S.; Augusto, G.; Martina, B.; Chang, X.; Nasrallah, G.; Speiser, D.E.; Vogel, M.; Bachmann, M.F.; Mohsen, M.O. Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron. Vaccines 2022, 10, 743. https://doi.org/10.3390/vaccines10050743

AMA Style

Vogt A-CS, Augusto G, Martina B, Chang X, Nasrallah G, Speiser DE, Vogel M, Bachmann MF, Mohsen MO. Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron. Vaccines. 2022; 10(5):743. https://doi.org/10.3390/vaccines10050743

Chicago/Turabian Style

Vogt, Anne-Cathrine S., Gilles Augusto, Byron Martina, Xinyue Chang, Gheyath Nasrallah, Daniel E. Speiser, Monique Vogel, Martin F. Bachmann, and Mona O. Mohsen. 2022. "Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron" Vaccines 10, no. 5: 743. https://doi.org/10.3390/vaccines10050743

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