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
Main Authors: Elko, Evan A., Nelson, Georgia A., Mead, Heather L., Kelley, Erin J., Carvalho, Sophia T., Sarbo, Nathan G., Harms, Caroline E., Le Verche, Virginia, Cardoso, Angelo A., Ely, Jennifer L., Boyle, Annalee S., Piña, Alejandra, Henson, Sierra N., Rahee, Fatima, Keim, Paul S., Celona, Kimberly R., Yi, Jinhee, Settles, Erik W., Bota, Daniela A., Yu, George C., Morris, Sheldon R., Zaia, John A., Ladner, Jason T., Altin, John A.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 05-07-2022
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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. [Display omitted] -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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ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.111022