Antibody evasion by the P.1 strain of SARS-CoV-2

DOI: 10.1016/j.cell.2021.03.055

Authors: Wanwisa Dejnirattisai (Wellcome Centre for Human Genetics, University of Oxford) , Daming Zhou (The Wellcome Centre for Human Genetics, University of Oxford) , 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)) , Alexander J. Mentzer (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Helen M. Ginn (University of Oxford) , Yuguang Zhao (Wellcome Centre for Human Genetics, University of Oxford) , Helen M. E. Duyvesteyn (Wellcome Centre for Human Genetics, University of Oxford) , Aekkachai Tuekprakhon (Wellcome Centre for Human Genetics, University of Oxford) , Rungtiwa Nutalai (Wellcome Centre for Human Genetics, University of Oxford) , Beibei Wang (Wellcome Centre for Human Genetics, University of Oxford) , Guido Paesen (Wellcome Centre for Human Genetics, University of Oxford) , César López-Camacho (Wellcome Centre for Human Genetics, University of Oxford) , Jose Slon-Campos (Wellcome Centre for Human Genetics, University of Oxford) , Thomas S. Walter (Wellcome Centre for Human Genetics, University of Oxford) , Donal Skelly (Oxford University Hospitals NHS Foundation Trust; University of Oxford) , Sue Ann Costa Clemens (University of Siena; University of Oxford) , Felipe Gomes Naveca (Instituto Leônidas e Maria Deane) , Valdinete Nascimento (Instituto Leônidas e Maria Deane) , Fernanda Nascimento (Instituto Leônidas e Maria Deane) , Cristiano Fernandes Da Costa (Fundação de Vigilância em Saúde do Amazonas) , Paola C. Resende (Laboratorio de vírus respiratórios- IOC/FIOCRUZ) , Alex Pauvolid-Correa (Laboratorio de vírus respiratórios- IOC/FIOCRUZ) , Marilda M. Siqueira (Laboratorio de vírus respiratórios- IOC/FIOCRUZ) , Christina Dold (NIHR Oxford Biomedical Research Centre; University of Oxford) , Robert Levin (Worthing Hospital) , Tao Dong (Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford; MRC Weatherall Institute of Molecular Medicine) , Andrew J. Pollard (NIHR Oxford Biomedical Research Centre; University of Oxford) , Julian C. Knight (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Derrick Crook (University of Oxford) , Teresa Lambe (Jenner Institute, University of Oxford) , Elizabeth Clutterbuck (NIHR Oxford Biomedical Research Centre; University of Oxford) , Sagida Bibi (NIHR Oxford Biomedical Research Centre; University of Oxford) , Amy Flaxman (Jenner Institute, University of Oxford) , Mustapha Bittaye (Jenner Institute, University of Oxford) , Sandra Belij-Rammerstorfer (Jenner Institute, University of Oxford) , Sarah Gilbert (Jenner Institute, University of Oxford) , Miles W. Carroll (Wellcome Centre for Human Genetics, University of Oxford; Public Health England (PHE)) , Paul Klenerman (Oxford University Hospitals NHS Foundation Trust; NIHR Oxford Biomedical Research Centre; University of Oxford) , Eleanor Barnes (Oxford University Hospitals NHS Foundation Trust; NIHR Oxford Biomedical Research Centre; University of Oxford) , Susanna J. Dunachie (Oxford University Hospitals NHS Foundation Trust; Mahidol-Oxford Tropical Medicine Research Unit, Thailand; University of Oxford) , Neil G. Paterson (Diamond Light Source) , Mark A. Williams (Diamond Light Source) , David R. Hall (Diamond Light Source) , Ruben J. G. Hulswit (Wellcome Centre for Human Genetics, University of Oxford) , Thomas A. Bowden (Wellcome Centre for Human Genetics, University of Oxford) , Elizabeth E. Fry (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); Mahidol University) , 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; Instruct-ERIC) , Gavin R. Screaton (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell

State: Published (Approved)
Published: March 2021
Diamond Proposal Number(s): 27009

Abstract: Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Discipline Tags:

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

Technical Tags:

Diffraction Macromolecular Crystallography (MX)