Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers

Shelley Klompus, Sigal Leviatan, Thomas Vogl, Roei D. Mazor, Iris N. Kalka, Liat Stoler Barak, Nachum Nathan, Ayelet Peres, Lihee Moss, Anastasia Godneva, Sharon Kagan Ben Tikva, Eilat Shinar, Hadas Cohen Dvashi, Ronen Gabizon, Nir London, Ron Diskin, Gur Yaari, Adina Weinberger, Ziv Shulman, Eran Segal

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish
Article numbereabe9950
JournalScience immunology
Issue number61
StatePublished - 29 Jul 2021

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