A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus

• Published in: Virus research 2024-07, Vol.345, p.199383-199383, Article 199383
• Main Authors: Lee, Ji Hyun, Kim, Ji Woong, Lee, Hee Eon, Song, Jin Young, Cho, Ah Hyun, Hwang, Jae Hyeon, Heo, Kyun, Lee, Sukmook
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Bispecific - chemistry; Antibodies, Bispecific - genetics; Antibodies, Bispecific - immunology; Antibodies, Bispecific - pharmacology; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Bispecific antibody; Coronavirus Infections - immunology; Coronavirus Infections - virology; Dipeptidyl Peptidase 4 - immunology; Humans; MERS-CoV; Mice; Middle East Respiratory Syndrome Coronavirus - immunology; Neutralization Tests; Neutralizing antibody; Phage display; Protein Binding; Receptor-binding domain; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2024.199383

•Isolation of human monoclonal antibodies (mAbs) against MERS-CoV RBD through phage display.•Development of potent bispecific antibodies (bsAbs) targeting the MERS-CoV RBD.•The efficacy of the parental mAb is surpassed by the enhanced neutralization of MERS-CoV achieved by the bsAb K207.C.•The dual-targeting strategy for the effective management of MERS-CoV. The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization. [Display omitted]