Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 심현보 | - |
dc.date.accessioned | 2024-02-15T16:31:05Z | - |
dc.date.available | 2024-02-15T16:31:05Z | - |
dc.date.issued | 2023 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.other | OAK-34292 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/267945 | - |
dc.description.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. | - |
dc.language | English | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.subject | bispecific antibody | - |
dc.subject | fusion peptide | - |
dc.subject | phage display | - |
dc.subject | receptor-binding domain | - |
dc.subject | SARS-CoV-2 | - |
dc.title | A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants | - |
dc.type | Article | - |
dc.relation.volume | 14 | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.journaltitle | FRONTIERS IN IMMUNOLOGY | - |
dc.identifier.doi | 10.3389/fimmu.2023.1271508 | - |
dc.identifier.wosid | WOS:001078023000001 | - |
dc.author.google | Kim, Ji Woong | - |
dc.author.google | Kim, Hyun Jung | - |
dc.author.google | Heo, Kyun | - |
dc.author.google | Lee, Yoonwoo | - |
dc.author.google | Jang, Hui Jeong | - |
dc.author.google | Lee, Ho-Young | - |
dc.author.google | Park, Jun Won | - |
dc.author.google | Cho, Yea Bin | - |
dc.author.google | Lee, Ji Hyun | - |
dc.author.google | Shin, Ha Gyeong | - |
dc.author.google | Yang, Ha Rim | - |
dc.author.google | Choi, Hye Lim | - |
dc.author.google | Shim, Hyun Bo | - |
dc.author.google | Lee, Sukmook | - |
dc.contributor.scopusid | 심현보(26635827900) | - |
dc.date.modifydate | 20240215124542 | - |