Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

DOI: 10.1016/j.cell.2022.05.014

Authors: Rungtiwa Nutalai (Wellcome Centre for Human Genetics, University of Oxford) , Daming Zhou (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Aekkachai Tuekprakhon (Wellcome Centre for Human Genetics, University of Oxford) , Helen M. Ginn (Diamond Light Source) , Piyada Supasa (Wellcome Centre for Human Genetics, 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) , Jiandong Huo (Wellcome Centre for Human Genetics, University of Oxford) , Alexander J. Mentzer (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Helen M. E. Duyvesteyn (Wellcome Centre for Human Genetics, University of Oxford) , Aiste Dijokaite-Guraliuc (Wellcome Centre for Human Genetics, University of Oxford) , 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 (Wellcome Centre for Human Genetics, 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) , Bede Constantinides (University of Oxford) , Hermione Webster (University of Oxford) , Nigel Temperton (University of Kent and Greenwich) , 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) , Derrick Crook (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) , Neil G. Paterson (Diamond Light Source) , Mark A. Williams (Diamond Light Source) , David R. Hall (Diamond Light Source) , Juthathip Mongkolsapaya (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford) , Elizabeth E. Fry (Wellcome Centre for Human Genetics, University of Oxford) , Wanwisa Dejnirattisai (Wellcome Centre for Human Genetics, University of Oxford) , Jingshan Ren (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); 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) , Christopher Conlon (ISARIC4C consortium) , Alexandra Deeks (ISARIC4C consortium) , John Frater (ISARIC4C consortium) , Lisa Frending (ISARIC4C consortium) , Siobhan Gardiner (ISARIC4C consortium) , Anni Jämsén (ISARIC4C consortium) , Katie Jeffery (ISARIC4C consortium) , Tom Malone (ISARIC4C consortium) , Eloise Phillips (ISARIC4C consortium) , Lucy Rothwell (ISARIC4C consortium) , Lizzie Stafford (ISARIC4C consortium)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell

State: Published (Approved)
Published: May 2022
Diamond Proposal Number(s): 27009 , 26983

Abstract: Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1 and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site, however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focussed in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains and many show broad reactivity with variants of concern.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , Krios I-Titan Krios I at Diamond

Added On: 25/05/2022 11:49

Discipline Tags:

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

Technical Tags:

Diffraction Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)