tetano
Editor, Senior Moderator
J Med Virol
. 2024 Mar;96(3):e29506.
doi: 10.1002/jmv.29506. Empowering SARS-CoV-2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides
Ji Woong Kim[SUP] 1 [/SUP], Ji Hyun Lee[SUP] 1 [/SUP], Hyun Jung Kim[SUP] 1 [/SUP], Kyun Heo[SUP] 1 2 3 [/SUP], Yoonwoo Lee[SUP] 4 [/SUP], Hui Jeong Jang[SUP] 4 [/SUP], Ho-Young Lee[SUP] 4 [/SUP], Jun Won Park[SUP] 5 [/SUP], Yea Bin Cho[SUP] 1 [/SUP], Ha Gyeong Shin[SUP] 1 [/SUP], Ha Rim Yang[SUP] 1 [/SUP], Hee Eon Lee[SUP] 1 [/SUP], Jin Young Song[SUP] 1 [/SUP], Sukmook Lee[SUP] 1 2 3 [/SUP]
Affiliations
With the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS-CoV-2 to host cell membranes and viral fusion. We developed pioneering IgG4-(HR2)[SUB]4[/SUB] bifunctional antibodies by creating immunoglobulin G4-based and phage display-derived human monoclonal antibodies (mAbs) that specifically bind to the SARS-CoV-2 receptor-binding domain, engineered with four heptad repeat 2 (HR2) peptides. Our in vitro experiments demonstrate the superior neutralization efficacy of these engineered antibodies against various SARS-CoV-2 variants, ranging from original SARS-CoV-2 strain to the recently emerged Omicron variants, as well as SARS-CoV, outperforming the parental mAb. Notably, intravenous monotherapy with the bifunctional antibody neutralizes a SARS-CoV-2 variant in a murine model without causing significant toxicity. In summary, this study unveils the significant potential of HR2 peptide-driven bifunctional antibodies as a potent and versatile strategy for mitigating SARS-CoV-2 infections. This approach offers a promising avenue for rapid development and management in the face of the continuously evolving SARS-CoV-2 variants, holding substantial promise for pandemic control.
Keywords: SARS-CoV-2; bifunctional antibody; heptad repeat 2 peptide; phage display; receptor-binding domain.
. 2024 Mar;96(3):e29506.
doi: 10.1002/jmv.29506. Empowering SARS-CoV-2 variant neutralization with a bifunctional antibody engineered with tandem heptad repeat 2 peptides
Ji Woong Kim[SUP] 1 [/SUP], Ji Hyun Lee[SUP] 1 [/SUP], Hyun Jung Kim[SUP] 1 [/SUP], Kyun Heo[SUP] 1 2 3 [/SUP], Yoonwoo Lee[SUP] 4 [/SUP], Hui Jeong Jang[SUP] 4 [/SUP], Ho-Young Lee[SUP] 4 [/SUP], Jun Won Park[SUP] 5 [/SUP], Yea Bin Cho[SUP] 1 [/SUP], Ha Gyeong Shin[SUP] 1 [/SUP], Ha Rim Yang[SUP] 1 [/SUP], Hee Eon Lee[SUP] 1 [/SUP], Jin Young Song[SUP] 1 [/SUP], Sukmook Lee[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 38445718
- DOI: 10.1002/jmv.29506
With the global pandemic and the continuous mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the need for effective and broadly neutralizing treatments has become increasingly urgent. This study introduces a novel strategy that targets two aspects simultaneously, using bifunctional antibodies to inhibit both the attachment of SARS-CoV-2 to host cell membranes and viral fusion. We developed pioneering IgG4-(HR2)[SUB]4[/SUB] bifunctional antibodies by creating immunoglobulin G4-based and phage display-derived human monoclonal antibodies (mAbs) that specifically bind to the SARS-CoV-2 receptor-binding domain, engineered with four heptad repeat 2 (HR2) peptides. Our in vitro experiments demonstrate the superior neutralization efficacy of these engineered antibodies against various SARS-CoV-2 variants, ranging from original SARS-CoV-2 strain to the recently emerged Omicron variants, as well as SARS-CoV, outperforming the parental mAb. Notably, intravenous monotherapy with the bifunctional antibody neutralizes a SARS-CoV-2 variant in a murine model without causing significant toxicity. In summary, this study unveils the significant potential of HR2 peptide-driven bifunctional antibodies as a potent and versatile strategy for mitigating SARS-CoV-2 infections. This approach offers a promising avenue for rapid development and management in the face of the continuously evolving SARS-CoV-2 variants, holding substantial promise for pandemic control.
Keywords: SARS-CoV-2; bifunctional antibody; heptad repeat 2 peptide; phage display; receptor-binding domain.