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A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability

BACKGROUND: Human adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use. METHODS: Herein, a monoclonal antibody sp...

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Autores principales: Chen, Lei, Lu, Jiansheng, Yue, Junjie, Wang, Rong, Du, Peng, Yu, Yunzhou, Guo, Jiazheng, Wang, Xi, Jiang, Yujia, Cheng, Kexuan, Yang, Zhixin, Zheng, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060833/
https://www.ncbi.nlm.nih.gov/pubmed/37006289
http://dx.doi.org/10.3389/fimmu.2023.1132822
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author Chen, Lei
Lu, Jiansheng
Yue, Junjie
Wang, Rong
Du, Peng
Yu, Yunzhou
Guo, Jiazheng
Wang, Xi
Jiang, Yujia
Cheng, Kexuan
Yang, Zhixin
Zheng, Tao
author_facet Chen, Lei
Lu, Jiansheng
Yue, Junjie
Wang, Rong
Du, Peng
Yu, Yunzhou
Guo, Jiazheng
Wang, Xi
Jiang, Yujia
Cheng, Kexuan
Yang, Zhixin
Zheng, Tao
author_sort Chen, Lei
collection PubMed
description BACKGROUND: Human adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use. METHODS: Herein, a monoclonal antibody specific for HAdV55, mAb 9-8, was isolated from an scFv-phage display library derived from mice immunized with the purified inactived-HAdV55 virions. By using ELISA and a virus micro-neutralization assay, we evaluated the binding and neutralizing activity of mAb 9-8 following humanization. Western blotting analysis and antigen-antibody molecular docking analysis were used to identify the antigenic epitopes that the humanized monoclonal antibody 9-8-h2 recognized. After that, their thermal stability was determined. RESULTS: MAb 9-8 showed potent neutralization activity against HAdV55. After humanization, the humanized neutralizing monoclonal antibody (9-8-h2) was identified to neutralize HAdV55 infection with an IC50 of 0.6050 nM. The mAb 9-8-h2 recognized HAdV55 and HAdV7 virus particles, but not HAdV4 particles. Although mAb 9-8-h2 could recognize HAdV7, it could not neutralize HAdV7. Furthermore, mAb 9-8-h2 recognized a conformational neutralization epitope of the fiber protein and the crucial amino acid residues (Arg 288, Asp 157, and Asn 200) were identified. MAb 9-8-h2 also showed favorable general physicochemical properties, including good thermostability and pH stability. CONCLUSIONS: Overall, mAb 9-8-h2 might be a promising molecule for the prevention and treatment of HAdV55.
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spelling pubmed-100608332023-03-31 A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability Chen, Lei Lu, Jiansheng Yue, Junjie Wang, Rong Du, Peng Yu, Yunzhou Guo, Jiazheng Wang, Xi Jiang, Yujia Cheng, Kexuan Yang, Zhixin Zheng, Tao Front Immunol Immunology BACKGROUND: Human adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use. METHODS: Herein, a monoclonal antibody specific for HAdV55, mAb 9-8, was isolated from an scFv-phage display library derived from mice immunized with the purified inactived-HAdV55 virions. By using ELISA and a virus micro-neutralization assay, we evaluated the binding and neutralizing activity of mAb 9-8 following humanization. Western blotting analysis and antigen-antibody molecular docking analysis were used to identify the antigenic epitopes that the humanized monoclonal antibody 9-8-h2 recognized. After that, their thermal stability was determined. RESULTS: MAb 9-8 showed potent neutralization activity against HAdV55. After humanization, the humanized neutralizing monoclonal antibody (9-8-h2) was identified to neutralize HAdV55 infection with an IC50 of 0.6050 nM. The mAb 9-8-h2 recognized HAdV55 and HAdV7 virus particles, but not HAdV4 particles. Although mAb 9-8-h2 could recognize HAdV7, it could not neutralize HAdV7. Furthermore, mAb 9-8-h2 recognized a conformational neutralization epitope of the fiber protein and the crucial amino acid residues (Arg 288, Asp 157, and Asn 200) were identified. MAb 9-8-h2 also showed favorable general physicochemical properties, including good thermostability and pH stability. CONCLUSIONS: Overall, mAb 9-8-h2 might be a promising molecule for the prevention and treatment of HAdV55. Frontiers Media S.A. 2023-03-16 /pmc/articles/PMC10060833/ /pubmed/37006289 http://dx.doi.org/10.3389/fimmu.2023.1132822 Text en Copyright © 2023 Chen, Lu, Yue, Wang, Du, Yu, Guo, Wang, Jiang, Cheng, Yang and Zheng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chen, Lei
Lu, Jiansheng
Yue, Junjie
Wang, Rong
Du, Peng
Yu, Yunzhou
Guo, Jiazheng
Wang, Xi
Jiang, Yujia
Cheng, Kexuan
Yang, Zhixin
Zheng, Tao
A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
title A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
title_full A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
title_fullStr A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
title_full_unstemmed A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
title_short A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
title_sort humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060833/
https://www.ncbi.nlm.nih.gov/pubmed/37006289
http://dx.doi.org/10.3389/fimmu.2023.1132822
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