A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75.

Abstract

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor affinity. ACE2 affinity for BA.2.75 is increased 9-fold compared with BA.2; there is also evidence of escape of BA.2.75 from immune serum, particularly that induced by Delta infection, which may explain the rapid spread in India, where where there is a high background of Delta infection. ACE2 affinity appears to be prioritized over greater escape.

• Authors: Jiandong Huo, Aiste Dijokaite-Guraliuc, Chang Liu, Daming Zhou, Helen M Ginn, Raksha Das, Piyada Supasa, Muneeswaran Selvaraj, Rungtiwa Nutalai, Aekkachai Tuekprakhon, Helen M E Duyvesteyn, Alexander J Mentzer, Donal Skelly, Thomas G Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Neil G Paterson, Mark A Williams, David R Hall, Megan Plowright, Thomas A H Newman, Hailey Hornsby, Thushan I de Silva, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J Dunachie, Andrew J Pollard, Teresa Lambe, Philip Goulder, OPTIC consortium, ISARIC4C consortium, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton
• Journal: Cell reports (Cell Rep) Vol. 42 Issue 1 Pg. 111903 (01 31 2023) ISSN: 2211-1247 [Electronic] United States
• PMID: 36586406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin-Converting Enzyme 2
• Antibodies

Topics

• Humans
• Angiotensin-Converting Enzyme 2
• COVID-19
• SARS-CoV-2
• Antibodies
• Hepatitis D