Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Cell
Christopher O BarnesPamela J Bjorkman

Abstract

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

References

Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W S PearD Baltimore
Mar 21, 1998·Journal of Molecular Biology·L J HarrisA McPherson
Feb 15, 2001·The Pediatric Infectious Disease Journal·S A Plotkin
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 27, 2005·Journal of Structural Biology·David N Mastronarde
Apr 7, 2006·The Journal of Biological Chemistry·Ponraj PrabakaranDimiter S Dimitrov
Sep 7, 2006·The Journal of Biological Chemistry·William C HwangRobert C Liddington
Sep 12, 2006·Journal of Structural Biology·Thomas D GoddardThomas E Ferrin
Jun 19, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Stanley A Plotkin
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 13, 2010·PloS One·Morgan N PriceAdam P Arkin
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 14, 2010·Clinical and Vaccine Immunology : CVI·Stanley A Plotkin
Jun 5, 2010·PLoS Pathogens·Joshua S Klein, Pamela J Bjorkman
Dec 7, 2010·Journal of Structural Biology·Benjamin W NeumanMichael J Buchmeier
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Jan 19, 2013·Molecular Biology and Evolution·Kazutaka Katoh, Daron M Standley
Nov 12, 2013·Nucleic Acids Research·James DunbarCharlotte M Deane
Nov 13, 2013·Nature Reviews. Microbiology·Rachel L GrahamRalph S Baric
Oct 2, 2014·The Journal of Pathology·Lisa E Gralinski, Ralph S Baric
Nov 8, 2014·Nucleic Acids Research·Marie-Paule LefrancSofia Kossida
Jul 29, 2015·Nature Communications·Lingshu WangBarney S Graham
Aug 19, 2015·Journal of Structural Biology·Alexis Rohou, Nikolaus Grigorieff
Mar 5, 2016·Methods : a Companion to Methods in Enzymology·James M BellSteven J Ludtke
Mar 5, 2016·Nature·Robert N KirchdoerferAndrew B Ward
Jun 28, 2016·Nature Reviews. Microbiology·Emmie de WitVincent J Munster
Sep 13, 2016·Nature Structural & Molecular Biology·Harry B GristickPamela J Bjorkman
Sep 16, 2016·Cell Host & Microbe·Melissa KanePaul D Bieniasz
Feb 7, 2017·Nature Methods·Ali PunjaniMarcus A Brubaker
Apr 7, 2017·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·Yuelong Shu, John McCauley
Aug 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jesper PallesenJason S McLellan
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alexandra C WallsDavid Veesler

❮ Previous
Next ❯

Citations

Jun 15, 2020·Allergy·Carmen RiggioniCezmi A Akdis
Jul 22, 2020·The Journal of Experimental Medicine·Fabian SchmidtPaul D Bieniasz
Jun 20, 2020·Nature·Davide F RobbianiMichel C Nussenzweig
Jul 15, 2020·Science·Meng YuanIan A Wilson
Jul 24, 2020·Nature Structural & Molecular Biology·Rory HendersonPriyamvada Acharya
Jul 28, 2020·Vaccines·Daniel E Speiser, Martin F Bachmann
Oct 13, 2020·Emerging Microbes & Infections·Benjamin MeyerChantal Reusken
Oct 13, 2020·Nature·Christopher O BarnesPamela J Bjorkman
Oct 29, 2020·ELife·Yiska WeisblumPaul D Bieniasz
Nov 20, 2020·The Journal of Experimental Medicine·Alexandra SchäferTimothy P Sheahan
Nov 25, 2020·Current Opinion in HIV and AIDS·Pilar MendozaChristian Gaebler
Dec 9, 2020·Science Translational Medicine·Zijun WangMichel C Nussenzweig
Dec 16, 2020·SLAS Discovery·Dawid MaciorowskiAdinarayana Kunamneni
Dec 22, 2020·Briefings in Bioinformatics·Vaishali P WamanChristine Orengo
Nov 21, 2020·The Journal of Clinical Investigation·Andrew I Flyak
Nov 4, 2020·The Journal of Infectious Diseases·Frauke MueckschPaul D Bieniasz
Dec 12, 2020·International Immunopharmacology·Hyun Jee HanSan Kim
Jan 6, 2021·Computational and Structural Biotechnology Journal·Edison OngYongqun He
Jan 14, 2021·The Biochemical Journal·George M Burslem
Oct 25, 2020·The Protein Journal·Mihaela Ileana Ionescu
Jan 28, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·George LagoumintzisKonstantinos Poulas
Jan 28, 2021·Cell Reports·Shuai LuRui-Tian Liu
Jan 7, 2021·Trends in Immunology·Liriye Kurtovic, James G Beeson
Jan 19, 2021·Nature·Christian GaeblerMichel C Nussenzweig
Dec 31, 2020·Journal of Molecular Cell Biology·Liu Daisy LiuFei-Long Meng
Dec 3, 2020·Frontiers in Microbiology·Shiu-Wan Chan
Nov 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wei LiDimiter S Dimitrov
Jan 7, 2021·Nature Structural & Molecular Biology·Robert J EdwardsPriyamvada Acharya
Jan 23, 2021·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Arnaud G L'HuillierUNKNOWN Geneva Centre for Emerging Viral Diseases
Jan 31, 2021·Trends in Immunology·Jennifer L Remmel, Margaret E Ackerman
Feb 17, 2021·Biomedical Journal·Juan Pablo Jaworski

❮ Previous
Next ❯

Datasets Mentioned

BETA
MN985325.1
AAP13441.1
JX869059.2
AAT84362.1
AAK32191.1
AAS58177.1
Q0ZME7.1
MN908947.3

Methods Mentioned

BETA
electron microscopy
ELISA
ELISAs
size-exclusion chromatography
transfection
Assay
glycosylation

Software Mentioned

Gen5
CTFFIND4
XDS
GraphPad
Prism
MATLAB
PHASER
PhyML
PyMOL
nsEMPEM

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.