Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Microbiology and Immunology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, USA.
J Clin Invest. 2022 Dec 1;132(23):e162282. doi: 10.1172/JCI162282.
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.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白是所有已批准的 COVID-19 疫苗中的主要抗原，也是单克隆抗体（mAb）治疗的唯一靶标。在 SARS-CoV-2 感染后会产生针对其他病毒抗原的免疫反应，但它们对抗病毒反应的贡献尚不清楚。在这里，我们探讨了核衣壳特异性抗体是否可以改善对 SARS-CoV-2 的保护作用。我们首先用核衣壳疫苗免疫小鼠，然后将来自这些小鼠的血清转移到未感染的小鼠中，然后用 SARS-CoV-2 进行挑战。我们表明，接受核衣壳特异性血清或核衣壳特异性 mAb 的小鼠对 SARS-CoV-2 的控制得到了增强。核衣壳特异性抗体引起 NK 介导的、针对感染细胞的抗体依赖性细胞毒性（ADCC）。据我们所知，这些发现首次在冠状病毒文献中证明，针对核衣壳蛋白的抗体反应可以改善病毒清除，为评估基于核衣壳的 mAb 治疗 COVID-19 的临床应用提供了依据。
