AUTHOR=Xie Jiajia , Ding Chengchao , He Jun , Zhang Yuqing , Ni Shuangshuang , Zhang Xiangyu , Chen Qingqing , Wang Jing , Huang Lina , He Hongliang , Li Wenting , Ma Huan , Jin Tengchuan , Zhang Siping , Gao Yong 

TITLE=Novel Monoclonal Antibodies and Recombined Antibodies Against Variant SARS-CoV-2

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.715464

DOI=10.3389/fimmu.2021.715464

ISSN=1664-3224

ABSTRACT=The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with 9 nAbs that were reconstructed by published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they are different from any of the 9 nAbs. Compared with XG81, XG83 exhibited high RBD binding affinity, neutralization potency against wild-typed pseudovirus, variant pseudoviruses with mutated spike proteins, such as D614G, E484Q and A475V, as well as authentic SARS-CoV-2 virus. To explore potential broadly neutralizing antibodies, heavy and light chains from all 18 nAbs (16 published nAbs, XG81 and XG83) were recombined, and studied for their RBD binding and affinity characteristics, neutralizing activity to pseudovirus and authentic SARS-CoV-2 virus. Interestingly, several recombined antibodies showed more potent neutralization activity to variant pseudoviruses than original paired Abs. Taken together, the novel neutralizing antibodies identified in this study are addition of candidate antibodies for development of clinical therapeutic agents against SARS-CoV-2 to minimize mutational escape.