Comparative Assessment of the Binding and Neutralisation Activity of Bispecific Antibodies Against SARS-CoV-2 Variants

Alexis Q Dean; Charles B Stauft; Julianne D Twomey; Joshua Tan; Luca Varani; Tony T Wang; Baolin Zhang

doi:10.1093/abt/tbac032

Comparative Assessment of the Binding and Neutralisation Activity of Bispecific Antibodies Against SARS-CoV-2 Variants

Antib Ther. 2022 Dec 29;6(1):49-58. doi: 10.1093/abt/tbac032. eCollection 2023 Jan.

Authors

Alexis Q Dean¹, Charles B Stauft², Julianne D Twomey¹, Joshua Tan³, Luca Varani⁴, Tony T Wang², Baolin Zhang¹

Affiliations

¹ Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
² Laboratory of Vector-Borne Viral Diseases, Division of Viral Products, Office of Vaccine Research and Review, Food and Drug Administration, White Oak, MD 20993, USA.
³ Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
⁴ Institute for Research in Biomedicine, University of Switzerland, CH-1015 Lausanne, Switzerland.

Abstract

Background: Neutralising 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 that require appropriate bioassays to ensure product quality and manufacturing consistency.

Methods: We developed procedures for biolayer interferometry (BLI) and a cell-based virus neutralisation assay, the focus reduction neutralisation test (FRNT). Using both assays, we tested a panel of five BsAbs against different spike variants (Ancestral, Delta and Omicron) to evaluate the use of these analytical methods in assessing binding and neutralisation activities of anti-SARS-CoV-2 therapeutics.

Results: We found comparable trends between BLI-derived binding affinity and FRNT-based virus neutralisation activity. Antibodies that displayed high binding affinity against a variant were often followed by potent neutralisation at lower concentrations, whereas those with low binding affinity also demonstrated reduced neutralisation activity.

Conclusion: The results support the utility of BLI and FRNT assays in measuring variant-specific binding and virus neutralisation activity of anti-SARS-CoV-2 antibodies.

Keywords: COVID-19; SARS-CoV-2; bioassay; bispecific antibody; product quality.