期刊
NATURE
卷 593, 期 7859, 页码 424-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03461-y
关键词
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资金
- European Union's Horizon 2020 research and innovation programme [101003650]
- SNF [31003A_182270]
- Lions Club Monteceneri
- George Mason University Fast Grant
- IRB start-up funds
- NIH [U01 AI151698, P01-AI138398-S1, 2U19AI111825]
- Caltech Merkin Institute for Translational Research
- Czech Ministry of Agriculture [RVO 68378050, RVO0518]
- Czech Ministry of Education, Youth and Sports [LM2018126, CZ.1.05/2.1.00/19.0395, CZ.1.05/1.1.00/02.0109, CZ.02.1.01/0.0/0.0/15_003/0000495]
- European Regional Development Fund [LM2018126, CZ.1.05/2.1.00/19.0395, CZ.1.05/1.1.00/02.0109, CZ.02.1.01/0.0/0.0/15_003/0000495]
- Czech Science Foundation [20-14325S]
- Bulgari Women & Science Fellowship in COVID-19 Research
- EU Joint Research Centre Exploratory Research program
- Ricerca Finalizzata from Ministry of Health, Italy [GR-201302358399]
- Czech Academy of Sciences [RVO 68378050, RVO0518]
- [R37-AI64003]
- [R01AI78788]
- [P50 AI150464]
- Swiss National Science Foundation (SNF) [31003A_182270] Funding Source: Swiss National Science Foundation (SNF)
The bispecific IgG1-like molecule CoV-X2 can simultaneously bind two independent sites on the RBD, prevent spike binding to ACE2, neutralize SARS-CoV-2 and its variants, and protect mice from disease in a mouse model of SARS-CoV-2 infection. This demonstrates the feasibility and efficacy of targeting non-overlapping RBD epitopes with IgG-like bispecific antibodies.
Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-19(1,2). A bispecific IgG1-like molecule (CoV-X2) has been developed on the basis of C121 and C135, two antibodies derived from donors who had recovered from COVID-19(3). Here we show that CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable spike binding to the cellular receptor of the virus, angiotensin-converting enzyme 2 (ACE2). Furthermore, CoV-X2 neutralizes wild-type SARS-CoV-2 and its variants of concern, as well as escape mutants generated by the parental monoclonal antibodies. We also found that in a mouse model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, the simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, and combines the advantages of antibody cocktails with those of single-molecule approaches.
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