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A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants
Yanyun Du1, Rui Shi2, Ying Zhang3
1Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Nature Communications
|August 18, 2021
Summary
A new monoclonal antibody, h11B11, effectively blocks SARS-CoV-2 and SARS-CoV by targeting ACE2. This antibody shows promise in preventing and treating COVID-19 and future coronavirus threats.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Emerging SARS-CoV-2 variants and resistance to therapeutics pose significant COVID-19 pandemic risks.
- Broadly effective therapies are crucial for limiting morbidity, mortality, and future transmissions of SARS-related coronaviruses.
Purpose of the Study:
- To isolate and characterize a humanized monoclonal antibody (h11B11) with potent inhibitory activity against SARS-CoV and SARS-CoV-2.
- To evaluate the therapeutic and prophylactic potential of h11B11 against SARS-CoV-2 in a preclinical model.
Main Methods:
- Isolation and humanization of an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), h11B11.
- Therapeutic and prophylactic administration of h11B11 in the hACE2 mouse model.
- Toxicology studies in cynomolgus monkeys and structural analysis of MAb/receptor complexes.
Main Results:
- h11B11 demonstrated potent inhibitory activity against SARS-CoV and global SARS-CoV-2 lineages.
- In vivo studies showed h11B11 alleviated and prevented SARS-CoV-2 replication and associated pathology.
- No significant adverse effects were observed in toxicology studies in non-human primates.
Conclusions:
- h11B11 effectively neutralizes SARS-CoV and SARS-CoV-2 by blocking ACE2 receptor binding.
- The antibody shows potential as a therapeutic countermeasure against current and future SARS-related coronavirus threats, including escape variants.
