Development of a neutralization monoclonal antibody with a broad neutralizing effect against SARS-CoV-2 variants
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Published:2023-12-01
Issue:1
Volume:20
Page:
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ISSN:1743-422X
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Container-title:Virology Journal
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language:en
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Short-container-title:Virol J
Author:
Ko Hae Li,Lee Deuk-ki,Kim Younghyeon,Jang Hui Jeong,Lee Youn Woo,Lee Ho-Young,Seok Sang-Hyuk,Park Jun Won,Limb Jin-Kyung,On Da In,Yun Jun-Won,Lyoo Kwang-Soo,Song Daesub,Yeom Minjoo,Lee Hanbyeul,Seong Je Kyung,Lee Sungjin
Abstract
Abstract
Background
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has challenged the effectiveness of current therapeutic regimens. Here, we aimed to develop a potent SARS-CoV-2 antibody with broad neutralizing effect by screening a scFv library with the spike protein receptor-binding domain (RBD) via phage display.
Methods
SKAI-DS84 was identified through phage display, and we performed pseudovirus neutralization assays, authentic virus neutralization assays, and in vivo neutralization efficacy evaluations. Furthermore, surface plasmon resonance (SPR) analysis was conducted to assess the physical characteristics of the antibody, including binding kinetics and measure its affinity for variant RBDs.
Results
The selected clones were converted to human IgG, and among them, SKAI-DS84 was selected for further analyses based on its binding affinity with the variant RBDs. Using pseudoviruses, we confirmed that SKAI-DS84 was strongly neutralizing against wild-type, B.1.617.2, B.1.1.529, and subvariants of SARS-CoV-2. We also tested the neutralizing effect of SKAI-DS84 on authentic viruses, in vivo and observed a reduction in viral replication and improved lung pathology. We performed binding and epitope mapping experiments to understand the mechanisms underlying neutralization and identified quaternary epitopes formed by the interaction between RBDs as the target of SKAI-DS84.
Conclusions
We identified, produced, and tested the neutralizing effect of SKAI-DS84 antibody. Our results highlight that SKAI-DS84 could be a potential neutralizing antibody against SARS-CoV-2 and its variants.
Funder
National Research Foundation of Korea Science and Industrial Technology in Gwangwon-do
Publisher
Springer Science and Business Media LLC
Subject
Infectious Diseases,Virology
Reference33 articles.
1. Cutler DM, Summers LH. The COVID-19 pandemic and the $16 trillion virus. JAMA. 2020;324:1495–6. 2. Gallagher KME, Leick MB, Larson RC, Berger TR, Katsis K, Yam JY, Brini G, Grauwet K. Collection MC-, processing T, Maus MV: SARS-CoV-2 T-cell immunity to variants of concern following vaccination. bioRxiv. 2021;27:113. 3. Liu L, Iketani S, Guo Y, Chan JF, Wang M, Liu L, Luo Y, Chu H, Huang Y, Nair MS, et al. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature. 2022;602:676–81. 4. VanBlargan LA, Errico JM, Halfmann PJ, Zost SJ, Crowe JE Jr, Purcell LA, Kawaoka Y, Corti D, Fremont DH, Diamond MS. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med. 2022;28:490–5. 5. Sun J, Yang ZD, Xie X, Li L, Zeng HS, Gong B, Xu JQ, Wu JH, Qu BB, Song GW. Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19. World J Clin Cases. 2023;11:2168–80.
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