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Updated: Sep 29, 2025
Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate
Franck Touret1, Cécile Baronti2, Hawa Sophia Bouzidi2
1Unité des Virus Émergents (UVE: Aix-Marseille University-IRD 190-Inserm 1207), Marseille, France. franck.touret@univ-amu.fr.
Abstract:
The emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6-fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.
Insights
The Omicron variant significantly reduces the effectiveness of most monoclonal antibody treatments for SARS-CoV-2. Sotrovimab retains some neutralizing activity, but Evusheld shows a substantial loss of efficacy.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- The Omicron variant of SARS-CoV-2 possesses numerous spike glycoprotein mutations, impacting therapeutic antibody effectiveness.
- Existing vaccines and antibody therapies face challenges due to Omicron's rapid global spread.
Purpose of the Study:
- To evaluate the neutralizing activity of eight monoclonal antibodies against the Omicron variant.
- To compare antibody efficacy against Omicron versus the ancestral SARS-CoV-2 strain.
Main Methods:
- Utilized a clinical strain of the Omicron variant for neutralization assays.
- Compared the activity of eight therapeutic monoclonal antibodies against Omicron and the B.1 BavPat1 D614G strain.
Main Results:
- Six of the eight tested monoclonal antibodies lost neutralizing activity against the Omicron variant.
- Sotrovimab demonstrated the least reduction in activity (3.1-fold change).
- Evusheld (cilgavimab/tixagevimab cocktail) showed a significant 42.6-fold reduction in efficacy, with tixagevimab retaining minimal activity.
Conclusions:
- Current monoclonal antibody therapies may have compromised clinical efficacy against the Omicron variant.
- Re-evaluation of therapeutic doses and consideration of alternative or combination therapies are warranted.
