Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• SARS-CoV-2 Omicron subvariants exhibit significant immune evasion from existing monoclonal antibodies (mAbs).
• Development of broad-spectrum neutralizing antibodies is critical for combating evolving viral threats.

Purpose of the Study:

• To isolate and characterize novel neutralizing antibodies against SARS-CoV-2 variants.
• To develop a potent, broad-spectrum antibody therapeutic for COVID-19.

Main Methods:

• Isolation of human monoclonal antibodies (mAbs) from engineered mice.
• Characterization of neutralizing activity against diverse SARS-CoV-2 variants.
• Cryo-electron microscopy for structural analysis.
• In vivo efficacy studies in mouse models.

Main Results:

• Two antibodies, BA7125 and BA7208, were identified with distinct neutralization profiles.
• A biparatopic antibody, BA7208/7125, demonstrated potent neutralization against all tested SARS-CoV-2 variants, including Omicron.
• Structural analysis revealed conserved binding sites on the spike protein.
• BA7208/7125 showed significant therapeutic and prophylactic efficacy in mouse models.

Conclusions:

• The biparatopic antibody BA7208/7125 offers broad-spectrum neutralization against current and emerging SARS-CoV-2 variants.
• BA7208/7125 represents a promising therapeutic candidate for COVID-19 prevention and treatment.