tetano
Editor, Senior Moderator
Microbiol Spectr
. 2021 Oct 27;e0141621.
doi: 10.1128/Spectrum.01416-21. Online ahead of print.
Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray
David Camerini[SUP] 1 2 [/SUP], Arlo Z Randall[SUP] 1 [/SUP], Krista Trappl-Kimmons[SUP] 1 [/SUP], Amit Oberai[SUP] 1 [/SUP], Christopher Hung[SUP] 1 [/SUP], Joshua Edgar[SUP] 1 [/SUP], Adam Shandling[SUP] 1 [/SUP], Vu Huynh[SUP] 1 [/SUP], Andy A Teng[SUP] 1 [/SUP], Gary Hermanson[SUP] 1 [/SUP], Jozelyn V Pablo[SUP] 1 [/SUP], Megan M Stumpf[SUP] 3 [/SUP], Sandra N Lester[SUP] 3 [/SUP], Jennifer Harcourt[SUP] 3 [/SUP], Azaibi Tamin[SUP] 3 [/SUP], Mohammed Rasheed[SUP] 3 [/SUP], Natalie J Thornburg[SUP] 3 [/SUP], Panayampalli S Satheshkumar[SUP] 3 [/SUP], Xiaowu Liang[SUP] 1 [/SUP], Richard B Kennedy[SUP] 4 [/SUP], Angela Yee[SUP] 1 [/SUP], Michael Townsend[SUP] #[/SUP][SUP] 3 [/SUP], Joseph J Campo[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; HCoV; SARS-CoV-2; antibody binding sites.
. 2021 Oct 27;e0141621.
doi: 10.1128/Spectrum.01416-21. Online ahead of print.
Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray
David Camerini[SUP] 1 2 [/SUP], Arlo Z Randall[SUP] 1 [/SUP], Krista Trappl-Kimmons[SUP] 1 [/SUP], Amit Oberai[SUP] 1 [/SUP], Christopher Hung[SUP] 1 [/SUP], Joshua Edgar[SUP] 1 [/SUP], Adam Shandling[SUP] 1 [/SUP], Vu Huynh[SUP] 1 [/SUP], Andy A Teng[SUP] 1 [/SUP], Gary Hermanson[SUP] 1 [/SUP], Jozelyn V Pablo[SUP] 1 [/SUP], Megan M Stumpf[SUP] 3 [/SUP], Sandra N Lester[SUP] 3 [/SUP], Jennifer Harcourt[SUP] 3 [/SUP], Azaibi Tamin[SUP] 3 [/SUP], Mohammed Rasheed[SUP] 3 [/SUP], Natalie J Thornburg[SUP] 3 [/SUP], Panayampalli S Satheshkumar[SUP] 3 [/SUP], Xiaowu Liang[SUP] 1 [/SUP], Richard B Kennedy[SUP] 4 [/SUP], Angela Yee[SUP] 1 [/SUP], Michael Townsend[SUP] #[/SUP][SUP] 3 [/SUP], Joseph J Campo[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
- PMID: 34704808
- DOI: 10.1128/Spectrum.01416-21
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.
Keywords: COVID-19; HCoV; SARS-CoV-2; antibody binding sites.