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The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes

Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both typ...

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Autores principales: Greaney, Allison J., Eguia, Rachel T., Starr, Tyler N., Khan, Khadija, Franko, Nicholas, Logue, Jennifer K., Lord, Sandra M., Speake, Cate, Chu, Helen Y., Sigal, Alex, Bloom, Jesse D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936118/
https://www.ncbi.nlm.nih.gov/pubmed/35313588
http://dx.doi.org/10.1101/2022.03.12.484088
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author Greaney, Allison J.
Eguia, Rachel T.
Starr, Tyler N.
Khan, Khadija
Franko, Nicholas
Logue, Jennifer K.
Lord, Sandra M.
Speake, Cate
Chu, Helen Y.
Sigal, Alex
Bloom, Jesse D.
author_facet Greaney, Allison J.
Eguia, Rachel T.
Starr, Tyler N.
Khan, Khadija
Franko, Nicholas
Logue, Jennifer K.
Lord, Sandra M.
Speake, Cate
Chu, Helen Y.
Sigal, Alex
Bloom, Jesse D.
author_sort Greaney, Allison J.
collection PubMed
description Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.
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spelling pubmed-89361182022-03-22 The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes Greaney, Allison J. Eguia, Rachel T. Starr, Tyler N. Khan, Khadija Franko, Nicholas Logue, Jennifer K. Lord, Sandra M. Speake, Cate Chu, Helen Y. Sigal, Alex Bloom, Jesse D. bioRxiv Article Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history. Cold Spring Harbor Laboratory 2022-03-14 /pmc/articles/PMC8936118/ /pubmed/35313588 http://dx.doi.org/10.1101/2022.03.12.484088 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Greaney, Allison J.
Eguia, Rachel T.
Starr, Tyler N.
Khan, Khadija
Franko, Nicholas
Logue, Jennifer K.
Lord, Sandra M.
Speake, Cate
Chu, Helen Y.
Sigal, Alex
Bloom, Jesse D.
The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
title The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
title_full The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
title_fullStr The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
title_full_unstemmed The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
title_short The SARS-CoV-2 Delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
title_sort sars-cov-2 delta variant induces an antibody response largely focused on class 1 and 2 antibody epitopes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936118/
https://www.ncbi.nlm.nih.gov/pubmed/35313588
http://dx.doi.org/10.1101/2022.03.12.484088
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