TY - JOUR
T1 - A delicate balance between antibody evasion and ACE2 affinity for Omicron BA.2.75
AU - OPTIC consortium
AU - ISARIC4C Investigators
AU - Huo, Jiandong
AU - Screaton, Gavin R.
AU - Fry, Elizabeth E.
AU - Mongkolsapaya, Juthathip
AU - Ren, Jingshan
AU - Stuart, David I.
AU - Green, Christopher
N1 - This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002), to D.I.S. and G.R.S. We are also grateful for support from Schmidt Futures, the Red Avenue Foundation, and the Oak Foundation. G.R.S. was supported by Wellcome. H.M.E.D., and J.R. are supported by Wellcome (101122/Z/13/Z) and D.I.S. and E.E.F. by the UKRI MRC (MR/N00065X/1). D.I.S. and G.R.S. are Jenner investigators. This is a contribution from the UK Instruct-ERIC Center. A.J.M. is an NIHR-supported academic clinical lecturer. The convalescent sampling was supported by the Medical Research Council (grant MC_PC_19059 awarded to the ISARIC4C Consortium with a full contributor list available at https://isaric4c.net/about/authors/), the National Institutes of Health, Oxford Biomedical Research Centre, and an Oxfordshire Health Services Research Committee grant to A.J.M. The Wellcome Center for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z). The computational aspects of this research were supported by the Wellcome Trust Core Award grant number 203141/Z/16/Z and the NIHR Oxford BRC. The Oxford Vaccine work was supported by UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical Research Network. We thank the Oxford Protective T-cell Immunology for COVID-19 (OPTIC) clinical team for participant sample collection and the Oxford Immunology Network COVID-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of Victoria, B.1.1.7, and B.1.351, which were isolated by scientists within the National Infection Service at PHE Porton Down, and the B.1.617.2 virus was kindly provided Wendy Barclay and T.I.d.S. We thank The Secretariat of National Surveillance, Ministry of Health Brazil, for assistance in obtaining P.1 samples. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T Cells to Covid-19 in Health Workers) Consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation. We acknowledge Diamond Light Source for time on Beamline I03 under Proposal lb27009 for COVID-19 Rapid Access. We thank the staff of the MRC Human Immunology Unit for access to their Biacore Facility. E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT222426/Z/21/Z and NIH (U19 I082360). S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). D.S. is an NIHR Academic Clinical Fellow. The Sheffield Teaching Hospitals Observational Study of Patients with Pulmonary Hypertension, Cardiovascular and Other Respiratory Diseases (STH-ObS) was supported by the British Heart Foundation (PG/11/116/29288). The STH-ObS Chief Investigator Allan Lawrie is supported by a British Heart Foundation Senior Basic Science Research fellowship (FS/18/52/33808). We gratefully acknowledge financial support from the UK Department of Health via the Sheffield NIHR Clinical Research Facility award to the Sheffield Teaching Hospitals Foundation NHS Trust. The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the National Institutes for Health Research (NIHR), the Medical Research Council (MRC), or Public Health, England.
PY - 2023/1/31
Y1 - 2023/1/31
N2 - 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.
AB - 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.
U2 - 10.1016/j.celrep.2022.111903
DO - 10.1016/j.celrep.2022.111903
M3 - Article
SN - 2211-1247
VL - 42
JO - Cell Reports
JF - Cell Reports
IS - 1
M1 - 111903
ER -