Comparative assessment of the binding and neutralization activity of bispecific antibodies against SARS-CoV-2 variants


 
 
 Neutralizing antibodies against SARS-CoV-2 are a vital component in the fight against COVID-19 pandemic, having the potential of both therapeutic and prophylactic applications. Bispecific antibodies (BsAbs) against SARS-CoV-2 are particularly promising given their ability to bind simultaneously to two distinct sites of the receptor binding domain (RBD) of the viral spike protein. Such antibodies are complex molecules associated with multi-faceted mechanisms of action (MoA) which require appropriate bioassays to ensure product quality and manufacturing consistency.
 
 
 
 We developed procedures for biolayer interferometry (BLI) and a cell-based virus neutralization assay, the focus reduction neutralization test (FRNT). Using both assays, we tested a panel of five bispecific antibodies (BsAbs) against different spike variants (Ancestral, Delta, and Omicron) to evaluate the use of these analytical methods in assessing binding and neutralization activities of anti-SARS-CoV-2 therapeutics.
 
 
 
 We found comparable trends between BLI-derived binding affinity and FRNT-based virus neutralization activity. Antibodies that displayed high binding affinity against a variant were often followed by potent neutralization at lower concentrations whereas those with low binding affinity also demonstrated reduced neutralization activity.
 
 
 
 The results support the utility of BLI and FRNT assays in measuring variant-specific binding and virus neutralization activity of anti-SARS-CoV-2 antibodies.
 
 
 
 Bispecific antibodies are a promising class of therapeutics against SARS-CoV-2. BLI coupled with FRNT assays can be used to characterize the binding and neutralization activity of these antibodies against specific SARS-CoV-2 variants.
