Protective Potential and Functional Role of Antibodies Against SARS-CoV-2 Nucleocapsid Protein

Background/Objectives: Cases of the new COVID-19 coronavirus 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 the 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. Methods: Protective effect of anti-N antibodies was studied in Syrian hamsters passively immunized with polyclonal sera raised to N(B.1) recombinant protein. Animals were infected with 105 or 104 TCID50 of SARS-CoV-2 (B.1, Wuhan or BA.2.86.1.1.18, Omicron) 6 hours after serum passive transfer, and protection was assessed by weight loss, clinical manifestation of disease, viral titers in respiratory tract, as well as by histopathological evaluation of lung tissues. Functional activity of anti-N (B.1) antibodies was evaluated by complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC) assays. Results: Protection of anti-N antibodies was evident only against 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 CDC and ADCC. Conclusions: 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.