Chapman Asheley P, Tang Xiaoling, Lee Joo R, Chida Asiya, Mercer Kristina, Wharton Rebekah E, Kainulainen Markus, Harcourt Jennifer L, Martines Roosecelis B, Schroeder Michelle, Zhao Liangjun, Bryksin Anton, Zhou Bin, Bergeron Eric, Bollweg Brigid C, Tamin Azaibi, Thornburg Natalie, Wentworth David E, Petway David, Bagarozzi Dennis A, Finn M G, Goldstein Jason M
School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr., Atlanta, GA, 30306, USA.
Immunodiagnostic Development Team/Reagent Diagnostic Services Branch (RDSB)/DSR/NCEZID/CDC, 1600 Clifton Rd NE., Atlanta, GA, 30333, USA.
Sci Rep. 2021 May 6;11(1):9682. doi: 10.1038/s41598-021-88809-0.
The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.
面对全球新冠疫情，对高亲和力、针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的单克隆抗体（mAb）的需求至关重要，因为此类试剂可具有重要的诊断、研究和治疗应用。由于其与许多细胞类型（尤其是肺上皮细胞）上存在的人类血管紧张素转换酶2（hACE2）受体的关键相互作用，刺突蛋白S1亚基内约300个氨基酸的受体结合域（RBD）最受关注。我们在此报告通过加速免疫和杂交瘤筛选过程产生的亲和力为29 nM的小鼠SARS-CoV-2单克隆抗体的开发和功能表征。不同的功能，包括与多种蛋白质表位的结合、病毒中和、对RBD-hACE2结合的影响以及对感染肺组织的免疫组织化学染色，与可变的基因使用和序列相关。
