Effective in vivo therapeutic IgG antibody against VP3 of enterovirus 71 with receptor-competing activity
| Autor: | Qiang Jia, Tao Meng, Qingyong Ng, Cheng-I Wang, Fang He, Vincent T. K. Chow, Jimmy Kwang, Wenjie Chin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular 030106 microbiology Virus Attachment Antibodies Viral Virus Neutralization Article 03 medical and health sciences Epitopes Mice Antigen Neutralization Tests Enterovirus 71 Enterovirus Infections Animals Humans Neutralizing antibody Antigens Viral Multidisciplinary biology Chemistry Immunization Passive Antibodies Monoclonal biology.organism_classification Virology Antibodies Neutralizing Enterovirus A Human Disease Models Animal 030104 developmental biology Capsid Immunoglobulin G biology.protein Receptors Virus Capsid Proteins Antibody Conformational epitope |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Passive immunization is an effective option for treatment against hand, foot and mouth disease caused by EV71, especially with cross-neutralizing IgG monoclonal antibodies. In this study, an EV71-specific IgG2a antibody designated 5H7 was identified and characterized. 5H7 efficiently neutralizes the major EV71 genogroups (A, B4, C2, C4). The conformational epitope of 5H7 was mapped to the highly conserved amino acid position 74 on VP3 capsid protein using escape mutants. Neutralization with 5H7 is mediated by the inhibition of viral attachment, as revealed by virus-binding and post-attachment assays. In a competitive pull-down assay with SCARB2, 5H7 blocks the receptor-binding site on EV71 for virus neutralization. Passive immunization of chimeric 5H7 protected 100% of two-week-old AG129 mice from lethal challenge with an EV71 B4 strain for both prophylactic and therapeutic treatments. In contrast, 10D3, a previously reported neutralizing antibody that takes effect after virus attachment, could only confer prophylactic protection. These results indicate that efficient interruption of viral attachment is critical for effective therapeutic activity with 5H7. This report documents a novel universal neutralizing IgG antibody for EV71 therapeutics and reveals the underlying mechanism. |
| Databáze: | OpenAIRE |
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