Expression and functional study of chimeric antibodies targeting SARS-CoV-2 receptor binding domain

SHI Huichun1, JIAO Fanke2, 3, XU Wei2, 3, CHEN Yongkang2, 3, LU Lu2, 3, ZOU Peng1

Journal of Microbes and Infections ›› 2023, Vol. 18 ›› Issue (1) : 2-12.

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Journal of Microbes and Infections ›› 2023, Vol. 18 ›› Issue (1) : 2-12. DOI: 10.3969/j.issn.1673-6184.2023.01.001
Original Article

Expression and functional study of chimeric antibodies targeting SARS-CoV-2 receptor binding domain

  • SHI Huichun1, JIAO Fanke2, 3, XU Wei2, 3, CHEN Yongkang2, 3, LU Lu2, 3, ZOU Peng1
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Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a serious impact on people’s health and lives. At present, SARS-CoV-2 is still widely spread, but effective treatments for SARS-CoV-2 are still limited. Therefore, it is of great significance to find broad-spectrum neutralizing antibodies to block SARS-CoV-2 infection. In this study, we successfully expressed and purified three human-mouse chimeric antibodies targeting receptor-binding domain (RBD) of SARS-CoV-2, and then the neutralizing activities of these antibodies against a variety of SARS-CoV-2 pseudoviruses and authentic virus were tested. The results showed that these three antibodies could specifically neutralize SARS-CoV-2 wild-type pseudovirus, and the IC50 values were 0.03 μg/mL, 0.06 μg/mL and 0.03 μg/mL, respectively. Furthermore, these antibodies exhibited broad-spectrum neutralizing activity against Alpha, Delta and Lambda pseudoviruses, and could also inhibit the replication of SARS-CoV-2 Delta authentic virus. Mechanism studies showed that these antibodies could block cell-cell fusion mediated by SARS-CoV-2 S protein, and K417, E484 and N501 on receptor-binding domain (RBD) may be the key sites for binding with these three antibodies.

Key words

Severe acute respiratory syndrome coronavirus 2 / Receptor-binding domain / Chimeric antibody / Neutralizing antibody

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SHI Huichun1, JIAO Fanke2, 3, XU Wei2, 3, CHEN Yongkang2, 3, LU Lu2, 3, ZOU Peng1. Expression and functional study of chimeric antibodies targeting SARS-CoV-2 receptor binding domain[J]. Journal of Microbes and Infections. 2023, 18(1): 2-12 https://doi.org/10.3969/j.issn.1673-6184.2023.01.001

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