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A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2
Abdelilah Majdoubi, … , Adrian B. McDermott, Pascal M. Lavoie
Abdelilah Majdoubi, … , Adrian B. McDermott, Pascal M. Lavoie
Published March 15, 2021
Citation Information: JCI Insight. 2021;6(8):e146316. https://doi.org/10.1172/jci.insight.146316.
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Research Article COVID-19 Immunology

A majority of uninfected adults show preexisting antibody reactivity against SARS-CoV-2

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Abstract

Preexisting cross-reactivity to SARS-CoV-2 occurs in the absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that about 0.6% of nontriaged adults from the greater Vancouver, Canada, area between May 17 and June 19, 2020, showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determined that more than 90% of uninfected adults showed antibody reactivity against the spike protein, receptor-binding domain (RBD), N-terminal domain (NTD), or the nucleocapsid (N) protein from SARS-CoV-2. This seroreactivity was evenly distributed across age and sex, correlated with circulating coronaviruses’ reactivity, and was partially outcompeted by soluble circulating coronaviruses’ spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike and to conserved nonstructural viral proteins. We conclude that most adults display preexisting antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.

Authors

Abdelilah Majdoubi, Christina Michalski, Sarah E. O’Connell, Sarah Dada, Sandeep Narpala, Jean Gelinas, Disha Mehta, Claire Cheung, Dirk F.H. Winkler, Manjula Basappa, Aaron C. Liu, Matthias Görges, Vilte E. Barakauskas, Mike Irvine, Jennifer Mehalko, Dominic Esposito, Inna Sekirov, Agatha N. Jassem, David M. Goldfarb, Steven Pelech, Daniel C. Douek, Adrian B. McDermott, Pascal M. Lavoie

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Figure 2

Specificity of SARS-CoV-2 antibody reactivity.

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Specificity of SARS-CoV-2 antibody reactivity.
(A and B) Competition of ...
(A and B) Competition of SARS-CoV-2 spike and RBD antibody reactivity by SARS-CoV-2 spike and RBD proteins (A) or by circulating coronaviruses (cCoVs) spike proteins (B). (C and D) Competition of cCoVs spike antibody reactivity by SARS-CoV-2 spike and RBD proteins (C) or cCoVs spike proteins (D). (E) Competition of SARS-CoV-2 spike antibody reactivity by SARS-CoV-2 spike and RBD proteins or cCoVs spike proteins, in COVID-19 convalescent sera (seropositive, n = 5), or sera from uninfected individuals who showed highest SARS-CoV-2 spike (n = 10) and high RBD (n = 9), or lowest SARS-CoV-2 spike and RBD antibody reactivity (all low; n = 10). All values represent the ratios of antibody reactivity in competed samples over the antibody reactivity measured in absence of competing proteins (dash line). One sample in the RBD-high group failed, and these data are not shown. In E, data are represented as boxes (25th to 75th percentile, line at median) and whiskers (minimum to maximum); comparisons were made using 2-tailed paired t tests.

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