The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210008, China.
Commun Biol. 2023 Apr 3;6(1):364. doi: 10.1038/s42003-023-04759-5.
Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future.
由于 SARS-CoV-2 的不断进化，出现了奥密克戎变异株，并表现出严重的免疫逃逸。刺突蛋白上关键抗原位点的大量突变，使得大量现有的抗体和疫苗对该变异株无效。因此，迫切需要开发高效的广谱中和治疗药物。在这里，我们描述了一种兔单克隆抗体（RmAb）1H1，它对奥密克戎亚谱系具有广谱中和效力，包括 BA.1、BA.1.1、BA.2、BA.2.12.1、BA.2.75、BA.3 和 BA.4/5。对 BA.1 刺突-1H1 Fab 复合物的低温电子显微镜（cryo-EM）结构测定表明，1H1 靶向 RBD 的一个高度保守区域，避开了大多数循环的奥密克戎突变，解释了其广谱中和效力。我们的研究结果表明 1H1 是一种有前途的 RmAb 模型，可用于设计广谱中和抗体，并为未来针对新出现的变异株开发治疗药物和有效疫苗提供了思路。
