tetano
Editor, Senior Moderator
Nat Immunol
. 2022 Feb 28.
doi: 10.1038/s41590-022-01138-w. Online ahead of print.
An engineered bispecific human monoclonal antibody against SARS-CoV-2
Zhaohui Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Shihua Li[SUP] #[/SUP][SUP] 1 [/SUP], Gen Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Weiyu Peng[SUP] #[/SUP][SUP] 1 3 [/SUP], Zhen Chang[SUP] 4 [/SUP], Xue Zhang[SUP] 4 [/SUP], Zheng Fan[SUP] 1 [/SUP], Yan Chai[SUP] 1 [/SUP], Feiran Wang[SUP] 1 5 [/SUP], Xin Zhao[SUP] 1 [/SUP], Dedong Li[SUP] 1 3 [/SUP], Rong Zhang[SUP] 1 6 [/SUP], Zhanlong He[SUP] 7 [/SUP], Weiwei Zou[SUP] 4 [/SUP], Ke Xu[SUP] 8 [/SUP], Wenwen Lei[SUP] 8 [/SUP], Peipei Liu[SUP] 8 [/SUP], Junfeng Hao[SUP] 9 [/SUP], Jingjing Zhang[SUP] 10 [/SUP], Litao Sun[SUP] 10 [/SUP], Guizhen Wu[SUP] 8 [/SUP], Shuguang Tan[SUP] 11 [/SUP], George Fu Gao[SUP] 12 [/SUP], Feng Gao[SUP] 13 14 [/SUP], Yan Wu[SUP] 15 16 [/SUP]
Affiliations
Abstract
The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires effective therapies against coronavirus disease 2019 (COVID-19), and neutralizing antibodies are a promising therapy. A noncompeting pair of human neutralizing antibodies (B38 and H4) blocking SARS-CoV-2 binding to its receptor, ACE2, have been described previously. Here, we develop bsAb15, a bispecific monoclonal antibody (bsAb) based on B38 and H4. bsAb15 has greater neutralizing efficiency than these parental antibodies, results in less selective pressure and retains neutralizing ability to most SARS-CoV-2 variants of concern (with more potent neutralizing activity against the Delta variant). We also selected for escape mutants of the two parental mAbs, a mAb cocktail and bsAb15, demonstrating that bsAb15 can efficiently neutralize all single-mAb escape mutants. Furthermore, prophylactic and therapeutic application of bsAb15 reduced the viral titer in infected nonhuman primates and human ACE2 transgenic mice. Therefore, this bsAb is a feasible and effective strategy to treat and prevent severe COVID-19.
. 2022 Feb 28.
doi: 10.1038/s41590-022-01138-w. Online ahead of print.
An engineered bispecific human monoclonal antibody against SARS-CoV-2
Zhaohui Li[SUP] #[/SUP][SUP] 1 2 [/SUP], Shihua Li[SUP] #[/SUP][SUP] 1 [/SUP], Gen Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Weiyu Peng[SUP] #[/SUP][SUP] 1 3 [/SUP], Zhen Chang[SUP] 4 [/SUP], Xue Zhang[SUP] 4 [/SUP], Zheng Fan[SUP] 1 [/SUP], Yan Chai[SUP] 1 [/SUP], Feiran Wang[SUP] 1 5 [/SUP], Xin Zhao[SUP] 1 [/SUP], Dedong Li[SUP] 1 3 [/SUP], Rong Zhang[SUP] 1 6 [/SUP], Zhanlong He[SUP] 7 [/SUP], Weiwei Zou[SUP] 4 [/SUP], Ke Xu[SUP] 8 [/SUP], Wenwen Lei[SUP] 8 [/SUP], Peipei Liu[SUP] 8 [/SUP], Junfeng Hao[SUP] 9 [/SUP], Jingjing Zhang[SUP] 10 [/SUP], Litao Sun[SUP] 10 [/SUP], Guizhen Wu[SUP] 8 [/SUP], Shuguang Tan[SUP] 11 [/SUP], George Fu Gao[SUP] 12 [/SUP], Feng Gao[SUP] 13 14 [/SUP], Yan Wu[SUP] 15 16 [/SUP]
Affiliations
- PMID: 35228696
- DOI: 10.1038/s41590-022-01138-w
Abstract
The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires effective therapies against coronavirus disease 2019 (COVID-19), and neutralizing antibodies are a promising therapy. A noncompeting pair of human neutralizing antibodies (B38 and H4) blocking SARS-CoV-2 binding to its receptor, ACE2, have been described previously. Here, we develop bsAb15, a bispecific monoclonal antibody (bsAb) based on B38 and H4. bsAb15 has greater neutralizing efficiency than these parental antibodies, results in less selective pressure and retains neutralizing ability to most SARS-CoV-2 variants of concern (with more potent neutralizing activity against the Delta variant). We also selected for escape mutants of the two parental mAbs, a mAb cocktail and bsAb15, demonstrating that bsAb15 can efficiently neutralize all single-mAb escape mutants. Furthermore, prophylactic and therapeutic application of bsAb15 reduced the viral titer in infected nonhuman primates and human ACE2 transgenic mice. Therefore, this bsAb is a feasible and effective strategy to treat and prevent severe COVID-19.