Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody.
Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody.
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DOI：
10.1172/jci162282
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发表时间：
2022-12-01
影响因子：
15.9
通讯作者：
Penaloza-MacMaster, Pablo
中科院分区：
文献类型：
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作者：
Dangi, Tanushree;Sanchez, Sarah;Class, Jacob;Richner, Michelle;Visvabharathy, Lavanya;Chung, Young Rock;Bentley, Kirsten;Stanton, Richard J.;Koralnik, Igor J.;Richner, Justin M.;Penaloza-MacMaster, Pablo
严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）的刺突蛋白是所有获批的新冠病毒疫苗中的主要抗原，也是单克隆抗体（mAb）疗法的唯一靶点。感染SARS - CoV - 2后会产生针对其他病毒抗原的免疫反应，但其对抗病毒反应的贡献仍不明确。在此，我们探究了核衣壳特异性抗体是否能够提高对SARS - CoV - 2的防护。我们首先用一种基于核衣壳的疫苗免疫小鼠，然后将这些小鼠的血清转移到未免疫的小鼠体内，接着用SARS - CoV - 2进行攻毒。我们发现，接受核衣壳特异性血清或核衣壳特异性单克隆抗体的小鼠对SARS - CoV - 2的控制能力增强。核衣壳特异性抗体引发了自然杀伤细胞介导的、抗体依赖的细胞毒性作用（ADCC）来对抗感染细胞。据我们所知，这些发现首次在冠状病毒相关文献中证明，针对核衣壳蛋白的抗体反应能够提高病毒清除率，为基于核衣壳的单克隆抗体疗法治疗新冠病毒的临床评估提供了理论依据。
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and is also the only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution to the antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine and then transferred sera from these mice into naive mice, followed by challenge with SARS-CoV-2. We show that mice that received nucleocapsid-specific sera or a nucleocapsid-specific mAb exhibited enhanced control of SARS-CoV-2. Nucleocapsid-specific antibodies elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) against infected cells. To our knowledge, these findings provide the first demonstration in the coronavirus literature that antibody responses specific to the nucleocapsid protein can improve viral clearance, providing a rationale for the clinical evaluation of nucleocapsid-based mAb therapies to treat COVID-19.