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A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants
- Title
- A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants
- Authors
- Kim, Ji Woong; Kim, Hyun Jung; Heo, Kyun; Lee, Yoonwoo; Jang, Hui Jeong; Lee, Ho-Young; Park, Jun Won; Cho, Yea Bin; Lee, Ji Hyun; Shin, Ha Gyeong; Yang, Ha Rim; Choi, Hye Lim; Shim, Hyun Bo; Lee, Sukmook
- Ewha Authors
- 심현보
- SCOPUS Author ID
- 심현보
- Issue Date
- 2023
- Journal Title
- FRONTIERS IN IMMUNOLOGY
- ISSN
- 1664-3224
- Citation
- FRONTIERS IN IMMUNOLOGY vol. 14
- Keywords
- bispecific antibody; fusion peptide; phage display; receptor-binding domain; SARS-CoV-2
- Publisher
- FRONTIERS MEDIA SA
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.3389/fimmu.2023.1271508
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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fimmu-14-1271508.pdf(2.16 MB)
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