Mary Wilson
Well-known member
Published:June 12, 2022
Accepted Date: 8 June 2022
(This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.)
DOI:https://doi.org/10.1016/j.celrep.2022.111022
Evan A. Elko, Georgia A. Nelson, Heather L. Mead, Erin J. Kelley, Sophia T. Carvalho, Nathan G. Sarbo, Caroline E. Harms, Virginia Le Verche, Angelo A. Cardoso, Jennifer L. Ely, Annalee S. Boyle, Alejandra Piña, Sierra N. Henson, Fatima Rahee, Paul S. Keim, Kimberly R. Celona, Jinhee Yi, Erik W. Settles, Daniela A. Bota, George C. Yu, Sheldon R. Morris, John A. Zaia, Jason T. Ladner, John A. Altin
Abstract
The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naïve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine- induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS- CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later timepoints. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.
https://www.cell.com/action/showPdf?pii=S2211-1247(22)00811-7
Accepted Date: 8 June 2022
(This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published
in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.)
DOI:https://doi.org/10.1016/j.celrep.2022.111022
Evan A. Elko, Georgia A. Nelson, Heather L. Mead, Erin J. Kelley, Sophia T. Carvalho, Nathan G. Sarbo, Caroline E. Harms, Virginia Le Verche, Angelo A. Cardoso, Jennifer L. Ely, Annalee S. Boyle, Alejandra Piña, Sierra N. Henson, Fatima Rahee, Paul S. Keim, Kimberly R. Celona, Jinhee Yi, Erik W. Settles, Daniela A. Bota, George C. Yu, Sheldon R. Morris, John A. Zaia, Jason T. Ladner, John A. Altin
Abstract
The COVID-19 pandemic has triggered the first widespread vaccination campaign against a coronavirus. Many vaccinated subjects are previously naïve to SARS-CoV-2, however almost all have previously encountered other coronaviruses (CoVs) and the role of this immunity in shaping the vaccine response remains uncharacterized. Here we use longitudinal samples and highly-multiplexed serology to identify mRNA-1273 vaccine- induced antibody responses against a range of CoV Spike epitopes, in both phylogenetically conserved and non-conserved regions. Whereas reactivity to SARS- CoV-2 epitopes shows a delayed but progressive increase following vaccination, we observe distinct kinetics for the endemic CoV homologs at conserved sites in Spike S2: these become detectable sooner and decay at later timepoints. Using homolog-specific antibody depletion and alanine-substitution experiments, we show that these distinct trajectories reflect an evolving cross-reactive response that can distinguish rare, polymorphic residues within these epitopes. Our results reveal mechanisms for the formation of antibodies with broad reactivity against CoVs.
https://www.cell.com/action/showPdf?pii=S2211-1247(22)00811-7