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

Vaccines

Gheyath Nasrallah¹  Xinyue Chang²  Gilles Augusto²  Anne-Cathrine S. Vogt²  Mona O. Mohsen²  Daniel E. Speiser²  Monique Vogel²  Martin F. Bachmann²  Byron Martina³ 

[1] Biomedical Research Complex, Qatar University, Doha P.O. Box 2713, Qatar;Department of BioMedical Research, University of Bern, 3010 Bern, Switzerland;Department of Viroscience, Erasmus Medical Center, 3015 Rotterdam, The Netherlands;

关键词: Omicron;    Delta;    SARS-CoV-2;    antibody;   

DOI  :  10.3390/vaccines10050743

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown