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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized
Ruei-Min Lu1, Kang-Hao Liang1, Hsiao-Ling Chiang1
1Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei, Taiwan.
Abstract:
The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.
Insights
New monoclonal antibodies targeting SARS-CoV-2 Omicron variants were developed. These antibodies show broad neutralization against multiple variants, offering potential as universal treatments for COVID-19.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- The COVID-19 pandemic persists due to emerging SARS-CoV-2 variants like Omicron.
- Omicron variants exhibit immune evasion, necessitating novel therapeutic antibodies.
- Existing antibody therapies are often ineffective against current SARS-CoV-2 strains.
Purpose of the Study:
- To develop broadly neutralizing monoclonal antibodies against SARS-CoV-2 variants, particularly Omicron.
- To identify novel antibody targets within the spike protein receptor-binding domain (RBD).
- To assess the therapeutic potential of these antibodies against current and future SARS-CoV-2 strains.
Main Methods:
- mRNA-lipid nanoparticle immunization to generate monoclonal antibodies.
- Binding and neutralization assays against various SARS-CoV-2 variants of concern.
- Epitope mapping of antibody binding sites on the spike protein RBD.
- Chimeric and humanized antibody development and efficacy testing.
Main Results:
- Five novel K-RBD-mAbs demonstrated potent binding and neutralization of all tested SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Omicron).
- Antibody epitopes were mapped to overlapping regions around Y453 and F486 on the spike protein RBD.
- Chimeric antibodies (K-RBD-chAbs) effectively neutralized Omicron BA.1 and BA.2 with low IC50 values (5.7-12.9 ng/mL).
- Humanized antibodies (K-RBD-hAb-60, -62) retained significant neutralizing activity against Omicron.
Conclusions:
- The developed therapeutic antibodies show broad efficacy against current and emerging SARS-CoV-2 variants, including Omicron sublineages.
- These antibodies represent promising candidates for universal COVID-19 treatments.
- Targeting specific RBD epitopes provides a strategy for developing next-generation antiviral therapies.
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