tetano
Editor, Senior Moderator
Antiviral Res
. 2020 Jul 10;104868.
doi: 10.1016/j.antiviral.2020.104868. Online ahead of print.
Immunoglobulin fragment F(ab') [SUB]2[/SUB] against RBD potently neutralizes SARS-CoV-2 in vitro
Xiaoyan Pan[SUP] 1 [/SUP], Pengfei Zhou[SUP] 2 [/SUP], Tiejiong Fan[SUP] 3 [/SUP], Yan Wu[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Xiaoyue Shi[SUP] 3 [/SUP], Weijuan Shang[SUP] 1 [/SUP], Lijuan Fang[SUP] 2 [/SUP], Xiaming Jiang[SUP] 4 [/SUP], Jian Shi[SUP] 2 [/SUP], Yuan Sun[SUP] 4 [/SUP], Shaojuan Zhao[SUP] 5 [/SUP], Rui Gong[SUP] 6 [/SUP], Ze Chen[SUP] 7 [/SUP], Gengfu Xiao[SUP] 8 [/SUP]
Affiliations
Abstract
COVID-19, which is caused by the emerging human coronavirus SARS-CoV-2, has become a global pandemic that poses a serious threat to human health. To date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. Herein, therapeutic antibodies for SARS-CoV-2 were obtained from hyperimmune equine plasma. First, a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) was obtained in gram-level quantities through high-cell density fermentation of Chinese hamster ovary cells. Then, the binding of the RBD to the SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, was verified by several biochemical methods. The efficacy of the RBD in triggering antibody response in vivo was subsequently tested in both mice and equines, and the results showed that the RBD triggered high-titer neutralizing antibody production in vivo. Immunoglobulin F(ab')[SUB]2[/SUB] fragments were prepared from equine antisera via removal of the Fc region from the immunoglobulins. Finally, a neutralization test with live virus demonstrated that RBD-specific F(ab')[SUB]2[/SUB] inhibited SARS-CoV-2 with an EC[SUB]50[/SUB] of 0.07 μg/ml and an EC[SUB]80[/SUB] of 0.18 μg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlight RBD-specific equine immunoglobulin F(ab')[SUB]2[/SUB] fragment as a candidate for the treatment of SARS-CoV-2.
Keywords: COVID-19; SARS-CoV-2; immunoglobulin fragment; neutralizing antibody; receptor-binding domain.
. 2020 Jul 10;104868.
doi: 10.1016/j.antiviral.2020.104868. Online ahead of print.
Immunoglobulin fragment F(ab') [SUB]2[/SUB] against RBD potently neutralizes SARS-CoV-2 in vitro
Xiaoyan Pan[SUP] 1 [/SUP], Pengfei Zhou[SUP] 2 [/SUP], Tiejiong Fan[SUP] 3 [/SUP], Yan Wu[SUP] 1 [/SUP], Jing Zhang[SUP] 2 [/SUP], Xiaoyue Shi[SUP] 3 [/SUP], Weijuan Shang[SUP] 1 [/SUP], Lijuan Fang[SUP] 2 [/SUP], Xiaming Jiang[SUP] 4 [/SUP], Jian Shi[SUP] 2 [/SUP], Yuan Sun[SUP] 4 [/SUP], Shaojuan Zhao[SUP] 5 [/SUP], Rui Gong[SUP] 6 [/SUP], Ze Chen[SUP] 7 [/SUP], Gengfu Xiao[SUP] 8 [/SUP]
Affiliations
- PMID: 32659292
- DOI: 10.1016/j.antiviral.2020.104868
Abstract
COVID-19, which is caused by the emerging human coronavirus SARS-CoV-2, has become a global pandemic that poses a serious threat to human health. To date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. Herein, therapeutic antibodies for SARS-CoV-2 were obtained from hyperimmune equine plasma. First, a recombinant SARS-CoV-2 spike protein receptor-binding domain (RBD) was obtained in gram-level quantities through high-cell density fermentation of Chinese hamster ovary cells. Then, the binding of the RBD to the SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, was verified by several biochemical methods. The efficacy of the RBD in triggering antibody response in vivo was subsequently tested in both mice and equines, and the results showed that the RBD triggered high-titer neutralizing antibody production in vivo. Immunoglobulin F(ab')[SUB]2[/SUB] fragments were prepared from equine antisera via removal of the Fc region from the immunoglobulins. Finally, a neutralization test with live virus demonstrated that RBD-specific F(ab')[SUB]2[/SUB] inhibited SARS-CoV-2 with an EC[SUB]50[/SUB] of 0.07 μg/ml and an EC[SUB]80[/SUB] of 0.18 μg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlight RBD-specific equine immunoglobulin F(ab')[SUB]2[/SUB] fragment as a candidate for the treatment of SARS-CoV-2.
Keywords: COVID-19; SARS-CoV-2; immunoglobulin fragment; neutralizing antibody; receptor-binding domain.