tetano
Editor, Senior Moderator
Small Methods
. 2022 Oct 27;e2200932.
doi: 10.1002/smtd.202200932. Online ahead of print.
An Engineered IgG-VHH Bispecific Antibody against SARS-CoV-2 and Its Variants
Hang Chi[SUP] 1 [/SUP], Lei Wang[SUP] 2 3 [/SUP], Chanjuan Liu[SUP] 4 [/SUP], Xiaohe Cheng[SUP] 1 [/SUP], Hailiang Zheng[SUP] 4 [/SUP], Lilang Lv[SUP] 5 [/SUP], Yongcong Tan[SUP] 4 [/SUP], Nana Zhang[SUP] 1 [/SUP], Suoqun Zhao[SUP] 1 [/SUP], Mei Wu[SUP] 1 [/SUP], Dan Luo[SUP] 1 [/SUP], Hongying Qiu[SUP] 1 [/SUP], Rui Feng[SUP] 2 [/SUP], Wangjun Fu[SUP] 2 3 [/SUP], Jie Zhang[SUP] 5 [/SUP], Xiaochuan Xiong[SUP] 1 [/SUP], Yifei Zhang[SUP] 1 [/SUP], Shulong Zu[SUP] 1 [/SUP], Qi Chen[SUP] 1 [/SUP], Qing Ye[SUP] 1 [/SUP], Xintian Yan[SUP] 4 [/SUP], Yuhao Hu[SUP] 4 [/SUP], Zhen Zhang[SUP] 4 [/SUP], Run Yan[SUP] 4 [/SUP], Jiangfeng Yin[SUP] 4 [/SUP], Pan Lei[SUP] 4 [/SUP], Wanjing Wang[SUP] 4 [/SUP], Guojun Lang[SUP] 4 [/SUP], Junbin Shao[SUP] 5 [/SUP], Yongqiang Deng[SUP] 1 [/SUP], Xiangxi Wang[SUP] 2 3 [/SUP], Chengfeng Qin[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies are shown to be effective therapeutics for providing coronavirus disease 2019 (COVID-19) protection. However, recurrent variants arise and facilitate significant escape from current antibody therapeutics. Bispecific antibodies (bsAbs) represent a unique platform to increase antibody breadth and to reduce neutralization escape. Herein, a novel immunoglobulin G-variable domains of heavy-chain-only antibody (IgG-VHH) format bsAb derived from a potent human antibody R15-F7 and a humanized nanobody P14-F8-35 are rationally engineered. The resulting bsAb SYZJ001 efficiently neutralizes wild-type SARS-CoV-2 as well as the alpha, beta, gamma, and delta variants, with superior efficacy to its parental antibodies. Cryo-electron microscopy structural analysis reveals that R15-F7 and P14-F8-35 bind to nonoverlapping epitopes within the RBD and sterically hindered ACE2 receptor binding. Most importantly, SYZJ001 shows potent prophylactic and therapeutic efficacy against SARS-CoV-2 in three established mouse models. Collectively, the current results demonstrate that the novel bsAb format is feasible and effective, suggesting great potential as an inspiring antiviral strategy.
Keywords: IgG; SARS-CoV-2; VHH; bispecific antibody; novel format.
. 2022 Oct 27;e2200932.
doi: 10.1002/smtd.202200932. Online ahead of print.
An Engineered IgG-VHH Bispecific Antibody against SARS-CoV-2 and Its Variants
Hang Chi[SUP] 1 [/SUP], Lei Wang[SUP] 2 3 [/SUP], Chanjuan Liu[SUP] 4 [/SUP], Xiaohe Cheng[SUP] 1 [/SUP], Hailiang Zheng[SUP] 4 [/SUP], Lilang Lv[SUP] 5 [/SUP], Yongcong Tan[SUP] 4 [/SUP], Nana Zhang[SUP] 1 [/SUP], Suoqun Zhao[SUP] 1 [/SUP], Mei Wu[SUP] 1 [/SUP], Dan Luo[SUP] 1 [/SUP], Hongying Qiu[SUP] 1 [/SUP], Rui Feng[SUP] 2 [/SUP], Wangjun Fu[SUP] 2 3 [/SUP], Jie Zhang[SUP] 5 [/SUP], Xiaochuan Xiong[SUP] 1 [/SUP], Yifei Zhang[SUP] 1 [/SUP], Shulong Zu[SUP] 1 [/SUP], Qi Chen[SUP] 1 [/SUP], Qing Ye[SUP] 1 [/SUP], Xintian Yan[SUP] 4 [/SUP], Yuhao Hu[SUP] 4 [/SUP], Zhen Zhang[SUP] 4 [/SUP], Run Yan[SUP] 4 [/SUP], Jiangfeng Yin[SUP] 4 [/SUP], Pan Lei[SUP] 4 [/SUP], Wanjing Wang[SUP] 4 [/SUP], Guojun Lang[SUP] 4 [/SUP], Junbin Shao[SUP] 5 [/SUP], Yongqiang Deng[SUP] 1 [/SUP], Xiangxi Wang[SUP] 2 3 [/SUP], Chengfeng Qin[SUP] 1 [/SUP]
Affiliations
- PMID: 36300882
- DOI: 10.1002/smtd.202200932
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies are shown to be effective therapeutics for providing coronavirus disease 2019 (COVID-19) protection. However, recurrent variants arise and facilitate significant escape from current antibody therapeutics. Bispecific antibodies (bsAbs) represent a unique platform to increase antibody breadth and to reduce neutralization escape. Herein, a novel immunoglobulin G-variable domains of heavy-chain-only antibody (IgG-VHH) format bsAb derived from a potent human antibody R15-F7 and a humanized nanobody P14-F8-35 are rationally engineered. The resulting bsAb SYZJ001 efficiently neutralizes wild-type SARS-CoV-2 as well as the alpha, beta, gamma, and delta variants, with superior efficacy to its parental antibodies. Cryo-electron microscopy structural analysis reveals that R15-F7 and P14-F8-35 bind to nonoverlapping epitopes within the RBD and sterically hindered ACE2 receptor binding. Most importantly, SYZJ001 shows potent prophylactic and therapeutic efficacy against SARS-CoV-2 in three established mouse models. Collectively, the current results demonstrate that the novel bsAb format is feasible and effective, suggesting great potential as an inspiring antiviral strategy.
Keywords: IgG; SARS-CoV-2; VHH; bispecific antibody; novel format.