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Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination

BACKGROUND: Control of the COVID-19 pandemic will rely on SARS-CoV-2 vaccine-elicited antibodies to protect against emerging and future variants; an understanding of the unique features of the humoral responses to infection and vaccination, including different vaccine platforms, is needed to achieve...

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Autores principales: Garrett, Meghan E., Galloway, Jared G., Wolf, Caitlin, Logue, Jennifer K., Franko, Nicholas, Chu, Helen Y., Matsen, Frederick A., Overbaugh, Julie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509098/
https://www.ncbi.nlm.nih.gov/pubmed/34642694
http://dx.doi.org/10.1101/2021.10.05.463210
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author Garrett, Meghan E.
Galloway, Jared G.
Wolf, Caitlin
Logue, Jennifer K.
Franko, Nicholas
Chu, Helen Y.
Matsen, Frederick A.
Overbaugh, Julie
author_facet Garrett, Meghan E.
Galloway, Jared G.
Wolf, Caitlin
Logue, Jennifer K.
Franko, Nicholas
Chu, Helen Y.
Matsen, Frederick A.
Overbaugh, Julie
author_sort Garrett, Meghan E.
collection PubMed
description BACKGROUND: Control of the COVID-19 pandemic will rely on SARS-CoV-2 vaccine-elicited antibodies to protect against emerging and future variants; an understanding of the unique features of the humoral responses to infection and vaccination, including different vaccine platforms, is needed to achieve this goal. METHODS: The epitopes and pathways of escape for Spike-specific antibodies in individuals with diverse infection and vaccination history were profiled using Phage-DMS. Principal component analysis was performed to identify regions of antibody binding along the Spike protein that differentiate the samples from one another. Within these epitope regions we determined potential escape mutations by comparing antibody binding of peptides containing wildtype residues versus peptides containing a mutant residue. RESULTS: Individuals with mild infection had antibodies that bound to epitopes in the S2 subunit within the fusion peptide and heptad-repeat regions, whereas vaccinated individuals had antibodies that additionally bound to epitopes in the N- and C-terminal domains of the S1 subunit, a pattern that was also observed in individuals with severe disease due to infection. Epitope binding appeared to change over time after vaccination, but other covariates such as mRNA vaccine dose, mRNA vaccine type, and age did not affect antibody binding to these epitopes. Vaccination induced a relatively uniform escape profile across individuals for some epitopes, whereas there was much more variation in escape pathways in in mildly infected individuals. In the case of antibodies targeting the fusion peptide region, which was a common response to both infection and vaccination, the escape profile after infection was not altered by subsequent vaccination. CONCLUSIONS: The finding that SARS-CoV-2 mRNA vaccination resulted in binding to additional epitopes beyond what was seen after infection suggests protection could vary depending on the route of exposure to Spike antigen. The relatively conserved escape pathways to vaccine-induced antibodies relative to infection-induced antibodies suggests that if escape variants emerge, they may be readily selected for across vaccinated individuals. Given that the majority of people will be first exposed to Spike via vaccination and not infection, this work has implications for predicting the selection of immune escape variants at a population level.
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spelling pubmed-85090982021-10-13 Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination Garrett, Meghan E. Galloway, Jared G. Wolf, Caitlin Logue, Jennifer K. Franko, Nicholas Chu, Helen Y. Matsen, Frederick A. Overbaugh, Julie bioRxiv Article BACKGROUND: Control of the COVID-19 pandemic will rely on SARS-CoV-2 vaccine-elicited antibodies to protect against emerging and future variants; an understanding of the unique features of the humoral responses to infection and vaccination, including different vaccine platforms, is needed to achieve this goal. METHODS: The epitopes and pathways of escape for Spike-specific antibodies in individuals with diverse infection and vaccination history were profiled using Phage-DMS. Principal component analysis was performed to identify regions of antibody binding along the Spike protein that differentiate the samples from one another. Within these epitope regions we determined potential escape mutations by comparing antibody binding of peptides containing wildtype residues versus peptides containing a mutant residue. RESULTS: Individuals with mild infection had antibodies that bound to epitopes in the S2 subunit within the fusion peptide and heptad-repeat regions, whereas vaccinated individuals had antibodies that additionally bound to epitopes in the N- and C-terminal domains of the S1 subunit, a pattern that was also observed in individuals with severe disease due to infection. Epitope binding appeared to change over time after vaccination, but other covariates such as mRNA vaccine dose, mRNA vaccine type, and age did not affect antibody binding to these epitopes. Vaccination induced a relatively uniform escape profile across individuals for some epitopes, whereas there was much more variation in escape pathways in in mildly infected individuals. In the case of antibodies targeting the fusion peptide region, which was a common response to both infection and vaccination, the escape profile after infection was not altered by subsequent vaccination. CONCLUSIONS: The finding that SARS-CoV-2 mRNA vaccination resulted in binding to additional epitopes beyond what was seen after infection suggests protection could vary depending on the route of exposure to Spike antigen. The relatively conserved escape pathways to vaccine-induced antibodies relative to infection-induced antibodies suggests that if escape variants emerge, they may be readily selected for across vaccinated individuals. Given that the majority of people will be first exposed to Spike via vaccination and not infection, this work has implications for predicting the selection of immune escape variants at a population level. Cold Spring Harbor Laboratory 2021-10-05 /pmc/articles/PMC8509098/ /pubmed/34642694 http://dx.doi.org/10.1101/2021.10.05.463210 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
Garrett, Meghan E.
Galloway, Jared G.
Wolf, Caitlin
Logue, Jennifer K.
Franko, Nicholas
Chu, Helen Y.
Matsen, Frederick A.
Overbaugh, Julie
Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination
title Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination
title_full Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination
title_fullStr Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination
title_full_unstemmed Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination
title_short Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination
title_sort comprehensive characterization of the antibody responses to sars-cov-2 spike protein after infection and/or vaccination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509098/
https://www.ncbi.nlm.nih.gov/pubmed/34642694
http://dx.doi.org/10.1101/2021.10.05.463210
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