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

Anne-Cathrine S Vogt; Gilles Augusto; Byron Martina; Xinyue Chang; Gheyath Nasrallah; Daniel E Speiser; Monique Vogel; Martin F Bachmann; Mona O Mohsen

doi:10.3390/vaccines10050743

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

Vaccines (Basel). 2022 May 9;10(5):743. doi: 10.3390/vaccines10050743.

Authors

Anne-Cathrine S Vogt^{1

2}, Gilles Augusto^{1

2

3}, Byron Martina^{4

5}, Xinyue Chang^{1

2}, Gheyath Nasrallah^{6

7}, Daniel E Speiser^{1

2}, Monique Vogel^{1

2}, Martin F Bachmann^{1

2

3}, Mona O Mohsen^{1

2

8}

Affiliations

¹ Department of BioMedical Research, University of Bern, 3010 Bern, Switzerland.
² Department of Immunology RI, University Hospital Bern, 3010 Bern, Switzerland.
³ The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
⁴ Department of Viroscience, Erasmus Medical Center, 3015 Rotterdam, The Netherlands.
⁵ Artemis Bio-Support, 2629 Delft, The Netherlands.
⁶ Biomedical Research Complex, Qatar University, Doha P.O. Box 2713, Qatar.
⁷ Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, Doha P.O. Box 2713, Qatar.
⁸ Saiba GmbH, 8808 Pfaeffikon, Switzerland.

Abstract

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.

Keywords: Delta; Omicron; SARS-CoV-2; antibody.

Grants and funding

This research was funded by Saiba, A.G., the Swiss National Science Foundation (SNF grants 31003_185114 and IZRPZO_194968).