Related Experiment Video
Updated: Oct 25, 2025
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Broad betacoronavirus neutralization by a stem helix-specific human antibody
Dora Pinto1, Maximilian M Sauer2, Nadine Czudnochowski3
1Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
Abstract:
The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.
Insights
Researchers identified five potent monoclonal antibodies (mAbs) that target the stem helix of betacoronaviruses, including SARS-CoV-2. One antibody, S2P6, demonstrates broad neutralization capabilities and reduces viral load in animal models, offering a promising avenue for pan-betacoronavirus vaccines.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Betacoronaviruses, including SARS-CoV-2, pose significant public health threats due to human spillovers and rapid variant emergence.
- The need for broad-spectrum coronavirus countermeasures is critical for pandemic preparedness.
Purpose of the Study:
- To identify and characterize cross-reactive monoclonal antibodies targeting the spike glycoproteins of multiple betacoronaviruses.
- To elucidate the structural and functional basis of broad neutralization by these antibodies.
Main Methods:
- Isolation and characterization of monoclonal antibodies from COVID-19 convalescent individuals.
- Structural studies (e.g., cryo-EM, X-ray crystallography) to determine antibody-antigen interactions.
- In vitro neutralization assays using pseudotyped viruses and functional assays in animal models (hamsters).
Main Results:
- Five monoclonal antibodies (mAbs) were identified that cross-react with the stem helix of various betacoronavirus spike glycoproteins.
- The S2P6 mAb exhibited broad neutralization against viruses from three subgenera by inhibiting membrane fusion.
- Structural analysis revealed the molecular basis for S2P6's extensive cross-reactivity.
- S2P6 demonstrated efficacy in reducing SARS-CoV-2 viral burden in hamsters via neutralization and Fc-mediated functions.
Conclusions:
- Stem helix antibodies, though rare and often narrow in specificity, can achieve broad neutralization through mechanisms like somatic mutation.
- These findings provide a foundation for structure-guided development of pan-betacoronavirus vaccines for widespread protection against diverse coronaviruses.
