Potent Neutralization Ability of a Human Monoclonal Antibody Against Serotype 1 Dengue Virus
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 peripher...
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Published in | Frontiers in microbiology Vol. 9; p. 1214 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
06.06.2018
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Dongsheng Zhou, Beijing Institute of Microbiology and Epidemiology, China This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology Reviewed by: Silvia Beatriz Boscardin, Universidade de São Paulo, Brazil; Alec Jay Hirsch, Oregon Health & Science University, United States; Zhaochun Chen, National Institutes of Health, United States; Ying Wang, Shanghai Institute of Immunology, China |
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2018.01214 |