Publication date: Sep 05, 2025
Bispecific antibodies (bsAbs) offer an alternative to monoclonal antibody (mAb) cocktails for addressing the loss of efficacy due to the rapid emergence of SARS-CoV-2 mutants. The structure and specificity of the parental antibodies influence the development of a highly neutralizing bsAb. To design an effective bsAb, the recognition of 44 single-chain fragment variable (scFv) antibodies against variants of SARS-CoV-2 was evaluated, along with an assessment of their ability to competitively bind to the receptor-binding domain (RBD) compared to the most potent neutralizing mAbs. From this analysis, three antibodies – 19n01, 01n21, and 01n27 – were identified for their broad recognition and non-competitive binding behavior. These antibodies were selected as the parental antibodies for the design of two bsAb. The bsAb bis L and bis H were engineered as IgG-scFv constructs, each with the secondary domain oriented differently to introduce new specificities. Both bsAbs retained the neutralizing capabilities of their parental antibodies in live-virus assays, neutralizing the Omicron variants BQ. 1.1 and XBB. 1.
| Concepts | Keywords |
|---|---|
| 01n21 | Bispecific antibodies |
| Antibodies | monoclonal antibodies |
| Cocktails | Omicron |
| Competitively | SARS-CoV-2 |
| Mutants |