Potent Neutralization Ability of a Human Monoclonal Antibody Against Serotype 1 Dengue Virus
| Autor: | Yun-Zhou Yu, Zhixin Yang, Jiansheng Lu, Peitang Huang, Binghui Xia, Xiaowei Zhou, Wang Rong |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.drug_class viruses 030106 microbiology lcsh:QR1-502 Dengue virus Monoclonal antibody medicine.disease_cause Microbiology lcsh:Microbiology Virus Neutralization 03 medical and health sciences antibody neutralization medicine Antibody-dependent enhancement antibody-dependent enhancement biology Chemistry virus diseases biochemical phenomena metabolism and nutrition Virology Fragment crystallizable region envelope protein 1G5 030104 developmental biology biology.protein dengue virus serotype 1 human monoclonal antibody Antibody Conformational epitope |
| Zdroj: | Frontiers in Microbiology, Vol 9 (2018) |
| ISSN: | 1664-302X |
| Popis: | The incidence of dengue virus (DENV) infections has been escalating in tropical and subtropical countries, but there are still no effective therapeutic options. In the present study, a DENV-1-specific human monoclonal antibody (HMAb), 1G5, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of dengue patients was found to have potent neutralization activity against serotype 1 DENV (DENV-1). Its neutralization activity against DENV-2 was not as strong, and it was almost absent for DENV-3 and DENV-4. The results showed that HMAb 1G5 only binds to the envelop protein of intact DENV-1 or the envelop protein under unheated and non-reducing conditions, and that it does not bind to recombinant envelope protein. This could mean that the antibody recognizes a conformational epitope of the envelope protein. Further, the findings showed that HMAb 1G5 potently neutralizes DENV-1 in both the pre- and post-attachment phases of the virus at low concentrations. In vivo studies showed that HMAb 1G5 provides protection from DENV-1 infection in a murine model. In addition, antibody-dependent enhancement that occurs at lower doses of the antibody was completely abrogated by the introduction of Leu-to-Ala mutations (1G5-LALA) or deletion of nine amino acids (1G5-9del) in the Fc region. Therefore, HMAb 1G5 shows promise as a safe and effective agent for prophylactic and therapeutic treatment of DENV-1 infection. |
| Databáze: | OpenAIRE |
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