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

Vogt, Anne-Cathrine S; Augusto, Gilles; Martina, Byron; Chang, Xinyue; Nasrallah, Gheyath; Speiser, Daniel E; Vogel, Monique; Bachmann, Martin F; Mohsen, Mona O (2022). Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron. Vaccines, 10(5) MDPI 10.3390/vaccines10050743

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology

UniBE Contributor:

Vogt, Anne-Cathrine Sarah, Sousa Augusto, Gilles Anderson, Chang, Xinyue, Speiser, Daniel Ernst, Vogel, Monique, Bachmann, Martin (B), Mohsen, Mona Omar Mahmoud

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2076-393X

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

30 May 2022 10:48

Last Modified:

29 Mar 2023 23:38

Publisher DOI:

10.3390/vaccines10050743

PubMed ID:

35632499

Uncontrolled Keywords:

Delta Omicron SARS-CoV-2 antibody

BORIS DOI:

10.48350/170317

URI:

https://boris.unibe.ch/id/eprint/170317

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