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Updated: Jul 21, 2025
Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS
Wan Ni Chia1, Chee Wah Tan1, Aaron Wai Kit Tan1
1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
Abstract:
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope.
Insights
New monoclonal antibodies (mAbs) targeting SARS-CoV-2 variants offer broad-spectrum protection. One antibody, E7, demonstrates superior neutralizing potency and breadth against sarbecoviruses, addressing a critical need for effective therapeutics.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants like Omicron exhibit immune escape, complicating pandemic control.
- Existing monoclonal antibodies (mAbs) often lack broad neutralizing activity against diverse sarbecoviruses, including animal strains.
Purpose of the Study:
- To isolate and characterize potent human monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of huACE2-dependent sarbecoviruses.
- To identify mAbs with broad-spectrum neutralizing activity against SARS-CoV-2 and related sarbecoviruses.
Main Methods:
- Isolation and characterization of mAbs from a SARS-CoV survivor vaccinated with BNT162b2.
- Assessment of neutralizing potency and breadth against huACE2-dependent sarbecoviruses.
- Mutagenesis studies and cryo-electron microscopy to determine antibody epitope and binding interactions.
Main Results:
- Six potent mAbs targeting the SARS-CoV-2 RBD were identified.
- One mAb, E7, demonstrated superior neutralizing potency and breadth against huACE2-dependent sarbecoviruses compared to previously reported mAbs.
- Structural studies revealed a unique RBD contact footprint for these mAbs, with E7 binding a quaternary structure-dependent epitope.
Conclusions:
- The identified mAbs, particularly E7, represent promising candidates for broad-spectrum therapeutics against sarbecoviruses.
- E7's unique binding mode offers a potential strategy for overcoming antibody resistance in SARS-CoV-2 variants and related viruses.
