tetano
Editor, Senior Moderator
Cell
. 2020 Jun 24;S0092-8674(20)30757-1.
doi: 10.1016/j.cell.2020.06.025. Online ahead of print.
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
Christopher O Barnes[SUP] 1 [/SUP], Anthony P West Jr[SUP] 1 [/SUP], Kathryn E Huey-Tubman[SUP] 1 [/SUP], Magnus A G Hoffmann[SUP] 1 [/SUP], Naima G Sharaf[SUP] 2 [/SUP], Pauline R Hoffman[SUP] 1 [/SUP], Nicholas Koranda[SUP] 1 [/SUP], Harry B Gristick[SUP] 1 [/SUP], Christian Gaebler[SUP] 3 [/SUP], Frauke Muecksch[SUP] 4 [/SUP], Julio C Cetrulo Lorenzi[SUP] 3 [/SUP], Shlomo Finkin[SUP] 3 [/SUP], Thomas H?ggl?f[SUP] 3 [/SUP], Arlene Hurley[SUP] 5 [/SUP], Katrina G Millard[SUP] 3 [/SUP], Yiska Weisblum[SUP] 4 [/SUP], Fabian Schmidt[SUP] 4 [/SUP], Theodora Hatziioannou[SUP] 4 [/SUP], Paul D Bieniasz[SUP] 6 [/SUP], Marina Caskey[SUP] 3 [/SUP], Davide F Robbiani[SUP] 3 [/SUP], Michel C Nussenzweig[SUP] 7 [/SUP], Pamela J Bjorkman[SUP] 8 [/SUP]
Affiliations
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 S1[SUP]A[/SUP] and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 ? 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.
Keywords: COVID-19; ELISA; Fab; IgG; MERS-CoV; SARS-CoV; SARS-CoV-2; convalescent plasma; coronavirus; electron microscopy.
. 2020 Jun 24;S0092-8674(20)30757-1.
doi: 10.1016/j.cell.2020.06.025. Online ahead of print.
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies
Christopher O Barnes[SUP] 1 [/SUP], Anthony P West Jr[SUP] 1 [/SUP], Kathryn E Huey-Tubman[SUP] 1 [/SUP], Magnus A G Hoffmann[SUP] 1 [/SUP], Naima G Sharaf[SUP] 2 [/SUP], Pauline R Hoffman[SUP] 1 [/SUP], Nicholas Koranda[SUP] 1 [/SUP], Harry B Gristick[SUP] 1 [/SUP], Christian Gaebler[SUP] 3 [/SUP], Frauke Muecksch[SUP] 4 [/SUP], Julio C Cetrulo Lorenzi[SUP] 3 [/SUP], Shlomo Finkin[SUP] 3 [/SUP], Thomas H?ggl?f[SUP] 3 [/SUP], Arlene Hurley[SUP] 5 [/SUP], Katrina G Millard[SUP] 3 [/SUP], Yiska Weisblum[SUP] 4 [/SUP], Fabian Schmidt[SUP] 4 [/SUP], Theodora Hatziioannou[SUP] 4 [/SUP], Paul D Bieniasz[SUP] 6 [/SUP], Marina Caskey[SUP] 3 [/SUP], Davide F Robbiani[SUP] 3 [/SUP], Michel C Nussenzweig[SUP] 7 [/SUP], Pamela J Bjorkman[SUP] 8 [/SUP]
Affiliations
- PMID: 32645326
- DOI: 10.1016/j.cell.2020.06.025
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 S1[SUP]A[/SUP] and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 ? 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.
Keywords: COVID-19; ELISA; Fab; IgG; MERS-CoV; SARS-CoV; SARS-CoV-2; convalescent plasma; coronavirus; electron microscopy.