Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests
The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccina...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/9/2041 |
| _version_ | 1797481305475121152 |
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| author | Alexandra Rak Svetlana Donina Yana Zabrodskaya Larisa Rudenko Irina Isakova-Sivak |
| author_facet | Alexandra Rak Svetlana Donina Yana Zabrodskaya Larisa Rudenko Irina Isakova-Sivak |
| author_sort | Alexandra Rak |
| collection | DOAJ |
| description | The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccinated with specific vaccines has been characterized in numerous studies, mainly using Spike protein-based serology tests. However, Spike protein and specifically its receptor-binding domain (RBD) are mutation-prone, suggesting the reduced sensitivity of the validated serology tests in detecting antibodies raised to variants of concern (VOC). The viral nucleocapsid (N) protein is more conserved compared to Spike, but little is known about cross-reactivity of the N-specific antibodies between the ancestral B.1 virus and different VOCs. Here, we generated recombinant N phosphoproteins from different SARS-CoV-2 strains and analyzed the magnitude of N-specific antibodies in COVID-19 convalescent sera using an in-house N-based ELISA test system. We found a strong positive correlation in the magnitude of anti-N (B.1) antibodies and antibodies specific to various VOCs in COVID-19-recovered patients, suggesting that the N-binding antibodies are highly cross-reactive, and the most immunogenic epitopes within this protein are not under selective pressure. Overall, our study suggests that the RBD-based serology tests should be timely updated to reflect the constantly evolving nature of the SARS-CoV-2 Spike protein, whereas the validated N-based test systems can be used for the analysis of sera from COVID-19 patients regardless of the strain that caused the infection. |
| first_indexed | 2024-03-09T22:13:12Z |
| format | Article |
| id | doaj.art-4b44e271fac64cfc9df32ef48e966fe7 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:13:12Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-4b44e271fac64cfc9df32ef48e966fe72023-11-23T19:28:34ZengMDPI AGViruses1999-49152022-09-01149204110.3390/v14092041Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology TestsAlexandra Rak0Svetlana Donina1Yana Zabrodskaya2Larisa Rudenko3Irina Isakova-Sivak4Institute of Experimental Medicine, Saint Petersburg 197022, RussiaInstitute of Experimental Medicine, Saint Petersburg 197022, RussiaInstitute of Experimental Medicine, Saint Petersburg 197022, RussiaInstitute of Experimental Medicine, Saint Petersburg 197022, RussiaInstitute of Experimental Medicine, Saint Petersburg 197022, RussiaThe emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccinated with specific vaccines has been characterized in numerous studies, mainly using Spike protein-based serology tests. However, Spike protein and specifically its receptor-binding domain (RBD) are mutation-prone, suggesting the reduced sensitivity of the validated serology tests in detecting antibodies raised to variants of concern (VOC). The viral nucleocapsid (N) protein is more conserved compared to Spike, but little is known about cross-reactivity of the N-specific antibodies between the ancestral B.1 virus and different VOCs. Here, we generated recombinant N phosphoproteins from different SARS-CoV-2 strains and analyzed the magnitude of N-specific antibodies in COVID-19 convalescent sera using an in-house N-based ELISA test system. We found a strong positive correlation in the magnitude of anti-N (B.1) antibodies and antibodies specific to various VOCs in COVID-19-recovered patients, suggesting that the N-binding antibodies are highly cross-reactive, and the most immunogenic epitopes within this protein are not under selective pressure. Overall, our study suggests that the RBD-based serology tests should be timely updated to reflect the constantly evolving nature of the SARS-CoV-2 Spike protein, whereas the validated N-based test systems can be used for the analysis of sera from COVID-19 patients regardless of the strain that caused the infection.https://www.mdpi.com/1999-4915/14/9/2041COVID-19SARS-CoV-2nucleocapsid phosphoproteinrecombinant proteincross-reactivityantibody tests |
| spellingShingle | Alexandra Rak Svetlana Donina Yana Zabrodskaya Larisa Rudenko Irina Isakova-Sivak Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests Viruses COVID-19 SARS-CoV-2 nucleocapsid phosphoprotein recombinant protein cross-reactivity antibody tests |
| title | Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests |
| title_full | Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests |
| title_fullStr | Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests |
| title_full_unstemmed | Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests |
| title_short | Cross-Reactivity of SARS-CoV-2 Nucleocapsid-Binding Antibodies and Its Implication for COVID-19 Serology Tests |
| title_sort | cross reactivity of sars cov 2 nucleocapsid binding antibodies and its implication for covid 19 serology tests |
| topic | COVID-19 SARS-CoV-2 nucleocapsid phosphoprotein recombinant protein cross-reactivity antibody tests |
| url | https://www.mdpi.com/1999-4915/14/9/2041 |
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