@article{5d5d87508964448794f608a24aaee884,
title = "Epitope profiling reveals binding signatures of SARS-CoV-2 immune response in natural infection and cross-reactivity with endemic human CoVs",
abstract = "A major goal of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets of the SARS-CoV-2 antibody response is critical for vaccine design, diagnostics, and development of therapeutics. Here, we develop a pan-coronavirus phage display library to map antibody binding sites at high resolution within the complete viral proteomes of all known human-infecting coronaviruses in patients with mild or moderate/severe coronavirus disease 2019 (COVID-19). We find that the majority of immune responses to SARS-CoV-2 are targeted to the spike protein, nucleocapsid, and ORF1ab and include sites of mutation in current variants of concern. Some epitopes are identified in the majority of samples, while others are rare, and we find variation in the number of epitopes targeted between individuals. We find low levels of SARS-CoV-2 cross-reactivity in individuals with no exposure to the virus and significant cross-reactivity with endemic human coronaviruses (CoVs) in convalescent sera from patients with COVID-19.",
keywords = "COVID-19, SARS-CoV-2, cross-reactivity, epitopes, phage-display, serology, variants",
author = "Stoddard, {Caitlin I.} and Jared Galloway and Chu, {Helen Y.} and Shipley, {Mackenzie M.} and Kevin Sung and Itell, {Hannah L.} and Wolf, {Caitlin R.} and Logue, {Jennifer K.} and Ariana Magedson and Garrett, {Meghan E.} and Crawford, {Katharine H.D.} and Uri Laserson and Matsen, {Frederick A.} and Julie Overbaugh",
note = "Funding Information: We extend gratitude to all study participants who contributed samples. We thank members of the Overbaugh, Matsen, and Chu labs for thoughtful discussion and advice. We thank the Fred Hutchinson Cancer Research Center (FHCRC) Genomics Core, especially Cassie Sather, for assistance with Illumina sequencing. We thank Trevor Bedford (FHCRC) for advice on strains to include in the pan-CoV phage library, Theodore Gobillot (FHCRC) for advice on phage library construction and immunoprecipitation, and Haidyn Weight for assistance with neutralization assays. This work was funded by NIH grants AI138709 (principal investigator [PI] J.O.) and R01 AI146028 and U19 AI128914 (PI F.A.M.). J.O. received support as the Endowed Chair for Graduate Education ( FHCRC ). The research of F.A.M. was supported in part by a Faculty Scholar grant from the Howard Hughes Medical Institute and the Simons Foundation . Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = may,
day = "25",
doi = "10.1016/j.celrep.2021.109164",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}