tetano
Editor, Senior Moderator
Virus Res
. 2024 Apr 30:199383.
doi: 10.1016/j.virusres.2024.199383. Online ahead of print. A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus
Ji Hyun Lee[SUP] 1 [/SUP], Ji Woong Kim[SUP] 1 [/SUP], Hee Eon Lee[SUP] 1 [/SUP], Jin Young Song[SUP] 1 [/SUP], Ah Hyun Cho[SUP] 1 [/SUP], Jae Hyeon Hwang[SUP] 1 [/SUP], Kyun Heo[SUP] 2 [/SUP], Sukmook Lee[SUP] 3 [/SUP]
Affiliations
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.
Keywords: Bispecific antibody; MERS-CoV; Neutralizing antibody; Phage display; Receptor-binding domain.
. 2024 Apr 30:199383.
doi: 10.1016/j.virusres.2024.199383. Online ahead of print. A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus
Ji Hyun Lee[SUP] 1 [/SUP], Ji Woong Kim[SUP] 1 [/SUP], Hee Eon Lee[SUP] 1 [/SUP], Jin Young Song[SUP] 1 [/SUP], Ah Hyun Cho[SUP] 1 [/SUP], Jae Hyeon Hwang[SUP] 1 [/SUP], Kyun Heo[SUP] 2 [/SUP], Sukmook Lee[SUP] 3 [/SUP]
Affiliations
- PMID: 38697296
- DOI: 10.1016/j.virusres.2024.199383
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.
Keywords: Bispecific antibody; MERS-CoV; Neutralizing antibody; Phage display; Receptor-binding domain.