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Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray.
Camerini, David; Randall, Arlo Z; Trappl-Kimmons, Krista; Oberai, Amit; Hung, Christopher; Edgar, Joshua; Shandling, Adam; Huynh, Vu; Teng, Andy A; Hermanson, Gary; Pablo, Jozelyn V; Stumpf, Megan M; Lester, Sandra N; Harcourt, Jennifer; Tamin, Azaibi; Rasheed, Mohammed; Thornburg, Natalie J; Satheshkumar, Panayampalli S; Liang, Xiaowu; Kennedy, Richard B; Yee, Angela; Townsend, Michael; Campo, Joseph J.
  • Camerini D; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Randall AZ; University of California, Irvine, California, USA.
  • Trappl-Kimmons K; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Oberai A; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Hung C; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Edgar J; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Shandling A; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Huynh V; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Teng AA; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Hermanson G; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Pablo JV; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Stumpf MM; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Lester SN; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Harcourt J; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Tamin A; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Rasheed M; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Thornburg NJ; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Satheshkumar PS; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Liang X; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
  • Kennedy RB; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Yee A; Mayo Clinicgrid.66875.3a, Rochester, Minnesota, USA.
  • Townsend M; Antigen Discovery Incorporated (ADI), Irvine, California, USA.
  • Campo JJ; Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
Microbiol Spectr ; 9(2): e0141621, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1495015
Preprint
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ABSTRACT
The rapid worldwide spread of SARS-CoV-2 has accelerated research and development for controlling the COVID-19 pandemic. A multi-coronavirus protein microarray was created containing full-length proteins, overlapping protein fragments of various lengths, and peptide libraries from SARS-CoV-2 and four other human coronaviruses. Sera from confirmed COVID-19 patients as well as unexposed individuals were applied to multicoronavirus arrays to identify specific antibody reactivity. High-level IgG, IgM, and IgA reactivity to structural proteins S, M, and N of SARS-CoV-2, as well as accessory proteins such as ORF3a and ORF7a, were observed that were specific to COVID-19 patients. Antibody reactivity against overlapping 100-, 50-, and 30-amino acid fragments of SARS-CoV-2 proteins was used to identify antigenic regions. Numerous proteins of SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and the endemic human coronaviruses HCoV-NL63 and HCoV-OC43 were also more reactive with IgG, IgM, and IgA in COVID-19 patient sera than in unexposed control sera, providing further evidence of immunologic cross-reactivity between these viruses. Whereas unexposed individuals had minimal reactivity against SARS-CoV-2 proteins that poorly correlated with reactivity against HCoV-NL63 and HCoV-OC43 S2 and N proteins, COVID-19 patient sera had higher correlation between SARS-CoV-2 and HCoV responses, suggesting that de novo antibodies against SARS-CoV-2 cross-react with HCoV epitopes. Array responses were compared with validated spike protein-specific IgG enzyme-linked immunosorbent assays (ELISAs), showing agreement between orthologous methods. SARS-CoV-2 microneutralization titers were low in the COVID-19 patient sera but correlated with array responses against S and N proteins. The multi-coronavirus protein microarray is a useful tool for mapping antibody reactivity in COVID-19 patients. IMPORTANCE With novel mutant SARS-CoV-2 variants of concern on the rise, knowledge of immune specificities against SARS-CoV-2 proteins is increasingly important for understanding the impact of structural changes in antibody-reactive protein epitopes on naturally acquired and vaccine-induced immunity, as well as broader topics of cross-reactivity and viral evolution. A multi-coronavirus protein microarray used to map the binding of COVID-19 patient antibodies to SARS-CoV-2 proteins and protein fragments as well as to the proteins of four other coronaviruses that infect humans has shown specific regions of SARS-CoV-2 proteins that are highly reactive with patient antibodies and revealed cross-reactivity of these antibodies with other human coronaviruses. These data and the multi-coronavirus protein microarray tool will help guide further studies of the antibody response to COVID-19 and to vaccination against this worldwide pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus OC43, Human / Coronavirus NL63, Human / Middle East Respiratory Syndrome Coronavirus / SARS-CoV-2 / Antibodies, Viral / Epitopes Type of study: Randomized controlled trials Limits: Humans Language: English Journal: Microbiol Spectr Year: 2021 Document Type: Article Affiliation country: Spectrum.01416-21

Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus OC43, Human / Coronavirus NL63, Human / Middle East Respiratory Syndrome Coronavirus / SARS-CoV-2 / Antibodies, Viral / Epitopes Type of study: Randomized controlled trials Limits: Humans Language: English Journal: Microbiol Spectr Year: 2021 Document Type: Article Affiliation country: Spectrum.01416-21