Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein
Cases of new COVID-19 infection, which manifested in 2019 and caused a global socioeconomic crisis, still continue to be registered worldwide. The high mutational activity of SARS-CoV-2 leads to the emergence of new antigenic variants of the virus, which significantly reduces the effectiveness of CO...
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2025-05-01
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| author | Alexandra Rak Ekaterina Bazhenova Polina Prokopenko Victoria Matyushenko Yana Orshanskaya Konstantin V. Sivak Arina Kostromitina Larisa Rudenko Irina Isakova-Sivak |
| author_facet | Alexandra Rak Ekaterina Bazhenova Polina Prokopenko Victoria Matyushenko Yana Orshanskaya Konstantin V. Sivak Arina Kostromitina Larisa Rudenko Irina Isakova-Sivak |
| author_sort | Alexandra Rak |
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| description | Cases of new COVID-19 infection, which manifested in 2019 and caused a global socioeconomic crisis, still continue to be registered worldwide. The high mutational activity of SARS-CoV-2 leads to the emergence of new antigenic variants of the virus, which significantly reduces the effectiveness of COVID-19 vaccines, as well as the sensitivity of diagnostic test systems based on variable viral antigens. These problems may be solved by focusing on highly conserved coronavirus antigens, for example nucleocapsid (N) protein, which is actively expressed by coronavirus-infected cells and serves as a target for the production of virus-specific antibodies and T cell responses. It is known that anti-N antibodies are non-neutralizing, but their protective potential and functional activity are not sufficiently studied. Here, the protective effect of anti-N antibodies was studied in Syrian hamsters passively immunized with polyclonal sera raised to N(B.1) recombinant protein. The animals were infected with 10<sup>5</sup> or 10<sup>4</sup> TCID<sub>50</sub> of SARS-CoV-2 (B.1, Wuhan or BA.2.86.1.1.18, Omicron) 6 h after serum passive transfer, and protection was assessed by weight loss, clinical manifestation of disease, viral titers in the respiratory tract, as well as by the histopathological evaluation of lung tissues. The functional activity of anti-N(B.1) antibodies was evaluated by complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC) assays. The protection of anti-N antibodies was evident only against a lower dose of SARS-CoV-2 (B.1) challenge, whereas almost no protection was revealed against BA.2.86.1.1.18 variant. Anti-N(B.1) monoclonal antibodies were able to stimulate both CDC and ADCC. Thus, anti-N(B.1) antibodies possess protective activity against homologous challenge infection, which is possibly mediated by innate Fc-mediated immune reactions. These data may be informative for the development of N-based broadly protective COVID-19 vaccines. |
| format | Article |
| id | doaj-art-c57ab73c0b904130b6b0e14a66072440 |
| institution | Kabale University |
| issn | 2073-4468 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Antibodies |
| spelling | doaj-art-c57ab73c0b904130b6b0e14a660724402025-08-20T03:32:26ZengMDPI AGAntibodies2073-44682025-05-011424510.3390/antib14020045Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid ProteinAlexandra Rak0Ekaterina Bazhenova1Polina Prokopenko2Victoria Matyushenko3Yana Orshanskaya4Konstantin V. Sivak5Arina Kostromitina6Larisa Rudenko7Irina Isakova-Sivak8Institute of Experimental Medicine, St. Petersburg 197022, RussiaInstitute of Experimental Medicine, St. Petersburg 197022, RussiaInstitute of Experimental Medicine, St. Petersburg 197022, RussiaInstitute of Experimental Medicine, St. Petersburg 197022, RussiaSmorodintsev Research Institute of Influenza, St. Petersburg 197376, RussiaSmorodintsev Research Institute of Influenza, St. Petersburg 197376, RussiaInstitute of Experimental Medicine, St. Petersburg 197022, RussiaInstitute of Experimental Medicine, St. Petersburg 197022, RussiaInstitute of Experimental Medicine, St. Petersburg 197022, RussiaCases of new COVID-19 infection, which manifested in 2019 and caused a global socioeconomic crisis, still continue to be registered worldwide. The high mutational activity of SARS-CoV-2 leads to the emergence of new antigenic variants of the virus, which significantly reduces the effectiveness of COVID-19 vaccines, as well as the sensitivity of diagnostic test systems based on variable viral antigens. These problems may be solved by focusing on highly conserved coronavirus antigens, for example nucleocapsid (N) protein, which is actively expressed by coronavirus-infected cells and serves as a target for the production of virus-specific antibodies and T cell responses. It is known that anti-N antibodies are non-neutralizing, but their protective potential and functional activity are not sufficiently studied. Here, the protective effect of anti-N antibodies was studied in Syrian hamsters passively immunized with polyclonal sera raised to N(B.1) recombinant protein. The animals were infected with 10<sup>5</sup> or 10<sup>4</sup> TCID<sub>50</sub> of SARS-CoV-2 (B.1, Wuhan or BA.2.86.1.1.18, Omicron) 6 h after serum passive transfer, and protection was assessed by weight loss, clinical manifestation of disease, viral titers in the respiratory tract, as well as by the histopathological evaluation of lung tissues. The functional activity of anti-N(B.1) antibodies was evaluated by complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC) assays. The protection of anti-N antibodies was evident only against a lower dose of SARS-CoV-2 (B.1) challenge, whereas almost no protection was revealed against BA.2.86.1.1.18 variant. Anti-N(B.1) monoclonal antibodies were able to stimulate both CDC and ADCC. Thus, anti-N(B.1) antibodies possess protective activity against homologous challenge infection, which is possibly mediated by innate Fc-mediated immune reactions. These data may be informative for the development of N-based broadly protective COVID-19 vaccines.https://www.mdpi.com/2073-4468/14/2/45COVID-19 vaccineSARS-CoV-2Syrian hamsternucleocapsid proteinantiviral antibodies |
| spellingShingle | Alexandra Rak Ekaterina Bazhenova Polina Prokopenko Victoria Matyushenko Yana Orshanskaya Konstantin V. Sivak Arina Kostromitina Larisa Rudenko Irina Isakova-Sivak Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein Antibodies COVID-19 vaccine SARS-CoV-2 Syrian hamster nucleocapsid protein antiviral antibodies |
| title | Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein |
| title_full | Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein |
| title_fullStr | Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein |
| title_full_unstemmed | Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein |
| title_short | Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein |
| title_sort | protective potential and functional role of antibodies against sars cov 2 nucleocapsid protein |
| topic | COVID-19 vaccine SARS-CoV-2 Syrian hamster nucleocapsid protein antiviral antibodies |
| url | https://www.mdpi.com/2073-4468/14/2/45 |
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