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

DOI: 10.1016/j.celrep.2022.111903

Authors: Jiandong Huo (First Affiliated Hospital of Guangzhou Medical University; Wellcome Centre for Human Genetics, University of Oxford) , Aiste Dijokaite-Guraliuc (University of Oxford) , Chang Liu (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Raksha Das (Wellcome Centre for Human Genetics, University of Oxford) , Piyada Supasa (Wellcome Centre for Human Genetics, University of Oxford) , Muneeswaran Selvaraj (Wellcome Centre for Human Genetics, University of Oxford) , Rungtiwa Nutalai (Wellcome Centre for Human Genetics, University of Oxford) , Daming Zhou (The Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Alexander J. Mentzer (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Donal Skelly (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford) , Thomas G. Ritter (Oxford University Hospitals NHS Foundation Trust) , Ali Amini (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford) , Sagida Bibi (University of Oxford) , Sandra Adele (Oxford University Hospitals NHS Foundation Trust) , Sile Ann Johnson (Oxford University Hospitals NHS Foundation Trust) , Neil G. Paterson (Diamond Light Source) , Mark A. Williams (Diamond Light Source) , David R. Hall (Diamond Light Source) , Megan Plowright (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Thomas A. H. Newman (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Hailey Hornsby (University of Sheffield) , Thushan I. De Silva (University of Sheffield; Sheffield Teaching Hospitals NHS Foundation Trust) , Nigel Temperton (University of Kent and Greenwich Chatham Maritime) , Paul Klenerman (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford; NIHR Oxford Biomedical Research Centre) , Eleanor Barnes (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford; NIHR Oxford Biomedical Research Centre) , Susanna J. Dunachie (Oxford University Hospitals NHS Foundation Trust; Peter Medawar Building for Pathogen Research; University of Oxford; University of Oxford) , Andrew J. Pollard (University of Oxford; NIHR Oxford Biomedical Research Centre) , Teresa Lambe (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Philip Goulder (Peter Medawar Building for Pathogen Research; University of Oxford) , Elizabeth E. Fry (The Wellcome Centre for Human Genetics, University of Oxford) , Juthathip Mongkolsapaya (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Jingshan Ren (The Wellcome Centre for Human Genetics, University of Oxford) , David I. Stuart (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; Diamond Light Source) , Gavin R. Screaton (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Reports

State: Published (Approved)
Published: December 2022
Diamond Proposal Number(s): 27009

Abstract: Variants of 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 the 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 to 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 BA.2.75 is now the dominant variant. ACE2 affinity appears to be prioritised over greater escape.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 15/12/2022 15:28

Discipline Tags:

Vaccines Pathogens Infectious Diseases Health & Wellbeing Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)