Piepenbrink Michael S, Khalil Ahmed Magdy, Chang Ana, Mostafa Ahmed, Basu Madhubanti, Sarkar Sanghita, Panjwani Simran, Ha Yaelyn H, Ma Yao, Ye Chengjin, Wang Qian, Green Todd J, Kizziah James L, Erdmann Nathaniel B, Goepfert Paul A, Liu Lihong, Ho David D, Martinez-Sobrido Luis, Walter Mark R, Kobie James J
Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL USA.
Department of Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX USA.
Npj Viruses. 2024;2(1):55. doi: 10.1038/s44298-024-00063-z. Epub 2024 Nov 14.
SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. By increasing herd immunity, current vaccines have improved infection outcomes for many. However, prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a differential staining strategy with a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) - ACE2 fusion protein and a native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan-1, the more recent Omicron JN.1 strain, and SARS-CoV. 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain. Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）仍然是一项公共卫生负担，部分原因是其抗原不断多样化并导致新变种出现。通过提高群体免疫力，目前的疫苗改善了许多人的感染情况。然而，仍需要不受刺突蛋白病毒进化影响的预防和治疗干预措施。我们采用差异染色策略，使用合理设计的SARS-CoV-2受体结合域（RBD）-血管紧张素转换酶2（ACE2）融合蛋白和天然奥密克戎RBD蛋白，从一名感染SARS-CoV-2奥密克戎后的康复个体中开发出一种重组人单克隆抗体（hmAb）。所产生的hmAb 1301B7能有效中和多种SARS-CoV-2变种，包括原始的武汉-1株、较新的奥密克戎JN.1毒株以及SARS-CoV。1301B7仅通过其VH1-69重链与RBD的ACE2结合位点接触。通过1301B7与奥密克戎变种的许多保守残基（包括Y501和H505）结合，实现了广泛的特异性。与其广泛的结合表位一致，1301B7能够有效降低上、下呼吸道的病毒载量，并保护小鼠免受奥密克戎XBB1.5和奥密克戎JN.1病毒的攻击。这些结果表明，1301B7在预防或治疗临床SARS-CoV-2感染以及指导基于RBD的通用SARS-CoV-2预防性疫苗和治疗方法的开发方面具有广阔潜力。
