COVID-19 vaccination elicits an evolving, cross-reactive antibody response to epitopes conserved with endemic coronavirus Spike proteins
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 re...
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Published in: | Cell reports (Cambridge) Vol. 40; no. 1; p. 111022 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Elsevier Inc
05-07-2022
The Author(s) Elsevier |
Subjects: | |
Online Access: | Get full text |
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Summary: | 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.
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-COVID-19 vaccine response targets both conserved and non-conserved spike sites-Reactivity to endemic epitopes emerges and decays sooner than SARS-CoV-2 epitopes-The response to conserved sites is dominated by antibodies that bind multiple species-Recognition of polymorphic residues within conserved sites evolves over time
Elko et al. use a multiplexed assay to track epitope-specific antibody responses to COVID-19 vaccination. They identify conserved sites where antibodies cross-recognize endemic coronaviruses, but with divergent kinetics compared to SARS-CoV-2. The evolving recognition of polymorphic residues within otherwise conserved sites may influence the formation of broadly neutralizing antibodies. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Lead contact |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2022.111022 |