Rak Alexandra, Bazhenova Ekaterina, Prokopenko Polina, Matyushenko Victoria, Orshanskaya Yana, Sivak Konstantin V, Kostromitina Arina, Rudenko Larisa, Isakova-Sivak Irina
Institute of Experimental Medicine, St. Petersburg 197022, Russia.
Smorodintsev Research Institute of Influenza, St. Petersburg 197376, Russia.
Antibodies (Basel). 2025 May 28;14(2):45. doi: 10.3390/antib14020045.
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 or 10 TCID 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.
2019年出现并引发全球社会经济危机的新型冠状病毒感染病例在全球范围内仍有登记。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的高突变活性导致该病毒出现新的抗原变体，这显著降低了新型冠状病毒肺炎（COVID-19）疫苗的有效性，以及基于可变病毒抗原的诊断检测系统的敏感性。通过关注高度保守的冠状病毒抗原，例如核衣壳（N）蛋白，这些问题可能会得到解决，该蛋白由冠状病毒感染的细胞积极表达，并作为产生病毒特异性抗体和T细胞反应的靶点。已知抗N抗体不具有中和作用，但其保护潜力和功能活性尚未得到充分研究。在此，研究了用针对N（B.1）重组蛋白产生的多克隆血清被动免疫的叙利亚仓鼠中抗N抗体的保护作用。在血清被动转移6小时后，用10或10半数组织培养感染剂量（TCID）的SARS-CoV-2（B.1、武汉株或BA.2.86.1.1.18、奥密克戎株）感染动物，并通过体重减轻、疾病临床表现、呼吸道病毒滴度以及肺组织的组织病理学评估来评估保护作用。通过补体依赖性细胞毒性（CDC）和抗体依赖性细胞毒性（ADCC）试验评估抗N（B.1）抗体的功能活性。抗N抗体的保护作用仅在较低剂量的SARS-CoV-2（B.1）攻击下明显，而对BA.2.86.1.1.18变体几乎没有保护作用。抗N（B.1）单克隆抗体能够刺激CDC和ADCC。因此，抗N（B.1）抗体对同源攻击感染具有保护活性，这可能是由先天性Fc介导的免疫反应介导的。这些数据可能为基于N的广泛保护性COVID-19疫苗的开发提供信息。
