Journal of virological methods · 2025
Evaluation of two IgG-scFv bispecific antibodies for neutralizing Omicron variants of SARS-CoV-2.
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Hinojosa-Trujillo Diana, Dehesa-Canseco Freddy, García-Vega Melissa, Mata-Haro Verónica, Solís-Hernández Mario, Reséndiz-Sandoval Mónica, Zuo Fanglei, Marcotte Harold, Hernández Jesús
Аннотация
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.