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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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Detalles Bibliográficos
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
Descripción
Sumario: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.