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Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research
Published on: September 8, 2023
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A Multivalent and Thermostable Nanobody Neutralizing SARS-CoV-2 Omicron (B.1.1.529)
Yuying Lu1,2,3,4,5, Qianlin Li1,2,3,4,5, Huahao Fan6
1One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.
International Journal of Nanomedicine
|January 26, 2023
Summary
Nanobodies targeting SARS-CoV-2 Omicron variants were developed and enhanced using a nanoplatform. The multivalent nanobody LS-B-B2 shows potent neutralization activity against Omicron, offering a potential therapeutic strategy.
Area of Science:
- Virology and Immunology
- Nanotechnology
- Protein Engineering
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants possess numerous spike protein mutations, reducing the effectiveness of current vaccines and monoclonal antibodies.
- Nanobodies derived from high-throughput screening of naïve libraries present a promising avenue for developing novel preventive and therapeutic antibodies against emerging viral strains.
Purpose of the Study:
- To screen and characterize nanobodies with neutralizing activity against SARS-CoV-2.
- To engineer multivalent nanobodies using the Aquifex aeolicus lumazine synthase (AaLS) nanoplatform.
- To evaluate the enhanced potency and potential therapeutic application of engineered nanobodies against SARS-CoV-2 Omicron variants.
Main Methods:
- Screening of four nanobodies specific to the SARS-CoV-2 receptor-binding domain (RBD) from a naïve phage display library.
- Evaluation of nanobody affinity and neutralization capacity using surface plasmon resonance, surrogate virus neutralization tests, and pseudovirus assays.
- Engineering of multivalent nanobodies by conjugating monovalent nanobodies to the AaLS protein cage nanoplatform.
Main Results:
- Three out of four nanobodies retained significant inhibitory activity against the Omicron (B.1.1.529) variant.
- Nanobody B-B2 demonstrated the highest neutralizing activity against Omicron pseudovirus (IC50 = 1.658 μg/mL).
- The multivalent nanobody LS-B-B2 exhibited improved antiviral potency against Omicron pseudovirus (IC50 = 0.653 μg/mL), potentially targeting conserved RBD epitopes.
Conclusions:
- The AaLS nanoplatform effectively presents nanobodies, enhancing their potency against SARS-CoV-2.
- The multivalent nanobody LS-B-B2 demonstrates significant potential as a therapeutic agent for neutralizing SARS-CoV-2 variants, including Omicron.
