Novel bispecific human antibody platform specifically targeting a fully open spike conformation potently neutralizes multiple SARS-CoV-2 variants

Kim, Ji Woong; Heo, Kyun; Kim, Hyun Jung; Yoo, Youngki; Cho, Hyun-Soo; Jang, Hui Jeong; Lee, Ho‐Young; Ko, In Young; Woo, Ju Rang; Cho, Yea Bin; Lee, Ji Hyun; Yang, Ha Rim; Shin, Ha Gyeong; Choi, Hye Lim; Hwang, Kyusang; Kim, Sokho; Kim, Hanseong; Chun, Kwangrok; Lee, Sukmook

doi:10.1016/j.antiviral.2023.105576

Cited by 8 publications

(6 citation statements)

References 47 publications

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“…While numerous bsAbs have been developed in the field of oncology to enhance antitumor activity, recent research focusing on bsAbs targeting the SARS-CoV-2 RBD indicates their potential effectiveness in the field of virology for enhanced virus neutralization ( De Gasparo et al, 2021 ; Yuan et al, 2022 ). In a previous study, we developed a bsAb for SARS-CoV-2, confirming its outstanding neutralizing efficacy and highlighting its potential as an efficient antibody platform ( Kim et al, 2023b ). This strategy, involving the simultaneous targeting of distinct viral antigens or epitopes using a combination of antibodies within a single bsAb, shows promise for effective virus management.…”

Section: Discussionmentioning

confidence: 72%

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

Lee,

Kim,

Lee

et al. 2024

Virus Research

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Section: Discussionmentioning

confidence: 72%

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

Lee,

Kim,

Lee

et al. 2024

Virus Research

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“…Another approach is to investigate different antibody formats, bispecific or multispecific, that can simultaneously and synergistically bind to multiple epitopes. 42 , 43 , 44 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 …”

Section: Discussionmentioning

confidence: 99%

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

Inoue,

Yamamoto,

Sato

et al. 2024

iScience

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“…In response to the ongoing emergence of new SARS-CoV-2 variants, the development of bsAbs targeting distinct regions within the spike protein represents a favorable strategy for managing COVID-19 (46)(47)(48). In this study, we introduced K203.A, a novel IgG4-based bsAb with several promising characteristics for therapeutic application.…”

Section: Discussionmentioning

confidence: 99%

A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants

Kim,

Heo

et al. 2023

Front. Immunol.

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IntroductionThe emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has caused unprecedented health and socioeconomic crises, necessitating the immediate development of highly effective neutralizing antibodies. Despite recent advancements in anti-SARS-CoV-2 receptor-binding domain (RBD)-specific monoclonal antibodies (mAbs) derived from convalescent patient samples, their efficacy against emerging variants has been limited. In this study, we present a novel dual-targeting strategy using bispecific antibodies (bsAbs) that specifically recognize both the SARS-CoV-2 RBD and fusion peptide (FP), crucial domains for viral attachment to the host cell membrane and fusion in SARS-CoV-2 infection. MethodsUsing phage display technology, we rapidly isolated FP-specific mAbs from an established human recombinant antibody library, identifying K107.1 with a nanomolar affinity for SARS-CoV-2 FP. Furthermore, we generated K203.A, a new bsAb built in immunoglobulin G4-(single-chain variable fragment)2 forms and demonstrating a high manufacturing yield and nanomolar affinity to both the RBD and FP, by fusing K102.1, our previously reported RBD-specific mAb, with K107.1. ResultsOur comprehensive in vitro functional analyses revealed that the K203.A bsAb significantly outperformed the parental RBD-specific mAb in terms of neutralization efficacy against SARS-CoV-2 variants. Furthermore, intravenous monotherapy with K203.A demonstrated potent in vivo neutralizing activity without significant in vivo toxicity in a mouse model infected with a SARS-CoV-2 variant. ConclusionThese findings present a novel bsAb dual-targeting strategy, directed at SARS-CoV-2 RBD and FP, as an effective approach for rapid development and management against continuously evolving SARS-CoV-2 variants.

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Novel bispecific human antibody platform specifically targeting a fully open spike conformation potently neutralizes multiple SARS-CoV-2 variants

Cited by 8 publications

References 47 publications

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

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

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants

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