TY - JOUR
T1 - Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers
AU - Klompus, Shelley
AU - Leviatan, Sigal
AU - Vogl, Thomas
AU - Mazor, Roei D.
AU - Kalka, Iris N.
AU - Barak, Liat Stoler
AU - Nathan, Nachum
AU - Peres, Ayelet
AU - Moss, Lihee
AU - Godneva, Anastasia
AU - Tikva, Sharon Kagan Ben
AU - Shinar, Eilat
AU - Dvashi, Hadas Cohen
AU - Gabizon, Ronen
AU - London, Nir
AU - Diskin, Ron
AU - Yaari, Gur
AU - Weinberger, Adina
AU - Shulman, Ziv
AU - Segal, Eran
N1 - Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.
PY - 2021/7/29
Y1 - 2021/7/29
N2 - The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. Although antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all 7 hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered patients with COVID-19 showed distinct changes compared with 260 unexposed prepandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered patients with COVID-19 who bind a shared motif of SARSCoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Using antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered patients with COVID-19 from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals after a future zoonotic transmission event.
AB - The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. Although antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all 7 hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered patients with COVID-19 showed distinct changes compared with 260 unexposed prepandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered patients with COVID-19 who bind a shared motif of SARSCoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Using antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered patients with COVID-19 from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals after a future zoonotic transmission event.
UR - http://www.scopus.com/inward/record.url?scp=85112210822&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.abe9950
DO - 10.1126/sciimmunol.abe9950
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C2 - 34326184
AN - SCOPUS:85112210822
SN - 2470-9468
VL - 6
JO - Science immunology
JF - Science immunology
IS - 61
M1 - eabe9950
ER -