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

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

doi:10.1016/j.celrep.2022.111903

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

Cell Rep. 2023 Jan 31;42(1):111903. doi: 10.1016/j.celrep.2022.111903. Epub 2022 Dec 14.

Authors

Jiandong Huo¹, Aiste Dijokaite-Guraliuc², Chang Liu³, Daming Zhou⁴, Helen M Ginn⁵, Raksha Das², Piyada Supasa², Muneeswaran Selvaraj², Rungtiwa Nutalai², Aekkachai Tuekprakhon², Helen M E Duyvesteyn⁶, Alexander J Mentzer⁷, Donal Skelly⁸, Thomas G Ritter⁹, Ali Amini¹⁰, Sagida Bibi¹¹, Sandra Adele⁹, Sile Ann Johnson⁹, Neil G Paterson⁵, Mark A Williams⁵, David R Hall⁵, Megan Plowright¹², Thomas A H Newman¹², Hailey Hornsby¹³, Thushan I de Silva¹², Nigel Temperton¹⁴, Paul Klenerman¹⁵, Eleanor Barnes¹⁵, Susanna J Dunachie¹⁶, Andrew J Pollard¹⁷, Teresa Lambe¹⁸, Philip Goulder¹⁹; OPTIC consortium; ISARIC4C consortium; Elizabeth E Fry²⁰, Juthathip Mongkolsapaya²¹, Jingshan Ren²², David I Stuart²³, Gavin R Screaton²⁴

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, the Wellcome Centre for Human Genetics, Oxford, UK; Guangzhou Laboratory, Bio-island, Guangzhou 510320, China. Electronic address: [email protected].
² Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
³ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
⁴ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, the Wellcome Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK.
⁵ Diamond Light Source, Ltd., Harwell Science and Innovation Campus, Didcot, UK.
⁶ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, the Wellcome Centre for Human Genetics, Oxford, UK.
⁷ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁸ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁹ Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
¹⁰ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
¹¹ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹² Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
¹³ Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
¹⁴ Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent and Greenwich Chatham Maritime, Kent ME4 4TB, UK.
¹⁵ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁶ Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Peter Medawar Building for Pathogen Research, Oxford, UK; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand; Department of Medicine, University of Oxford, Oxford, UK.
¹⁷ Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
¹⁸ Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
¹⁹ Peter Medawar Building for Pathogen Research, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK.
²⁰ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, the Wellcome Centre for Human Genetics, Oxford, UK. Electronic address: [email protected].
²¹ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Electronic address: [email protected].
²² Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, the Wellcome Centre for Human Genetics, Oxford, UK. Electronic address: [email protected].
²³ Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, the Wellcome Centre for Human Genetics, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK; Diamond Light Source, Ltd., Harwell Science and Innovation Campus, Didcot, UK. Electronic address: [email protected].
²⁴ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, Oxford, UK. Electronic address: [email protected].

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.

Keywords: ACE2 receptor; BA.2.75; COVID-19; CP: Immunology; CP: Microbiology; RBD; SARS-CoV-2; antigenic variation; immune escape; spike; variant; variant of concern.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Angiotensin-Converting Enzyme 2
Antibodies

Abstract

Publication types

MeSH terms

Substances

Grants and funding