Broad-Spectrum Engineered Multivalent Nanobodies Against SARS-CoV-1/2.

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• SARS-CoV-2 Omicron sublineages exhibit significant immune escape from existing neutralizing antibodies.
• Current antibody screening methods are insufficient against rapidly mutating coronaviruses.
• There is a critical need for broad-spectrum neutralizing antibodies effective against multiple SARS-CoV strains.

Purpose of the Study:

• To develop a comprehensive strategy for designing broad-spectrum neutralizing nanobodies against SARS-CoV-1 and SARS-CoV-2.
• To create novel nanobody libraries targeting conserved viral epitopes.
• To engineer multivalent nanobodies for enhanced neutralization efficacy.

Main Methods:

• De novo design of a fully human nanobody library.
• Camel immunization to generate a nanobody library.
• Construction of trivalent nanobodies by linking multiple nanobodies targeting non-overlapping epitopes.
• In vitro neutralization assays and in vivo animal model studies.

Main Results:

• A trivalent nanobody, B11-E8-F3, demonstrated broad-spectrum neutralization activity against SARS-CoV-1 and diverse SARS-CoV-2 variants.
• B11-E8-F3 exhibited potent preventive and therapeutic effects in animal models infected with authentic SARS-related viruses.
• The designed nanobodies effectively targeted conserved epitopes, enhancing their broad applicability.

Conclusions:

• The trivalent nanobody B11-E8-F3 represents a promising candidate for broad-spectrum prevention and treatment of SARS-CoV-1 and SARS-CoV-2 infections.
• This approach offers a viable strategy for developing effective antibody therapies, particularly for high-risk populations.
• Nanobody engineering targeting conserved epitopes is a powerful tool against rapidly evolving viruses.