Development of a humanized antibody with high therapeutic potential against dengue virus type 2.

PLoS Neglected Tropical Diseases
Pi-Chun LiHan-Chung Wu

Abstract

Dengue virus (DENV) is a significant public health threat in tropical and subtropical regions of the world. A therapeutic antibody against the viral envelope (E) protein represents a promising immunotherapy for disease control. We generated seventeen novel mouse monoclonal antibodies (mAbs) with high reactivity against E protein of dengue virus type 2 (DENV-2). The mAbs were further dissected using recombinant E protein domain I-II (E-DI-II) and III (E-DIII) of DENV-2. Using plaque reduction neutralization test (PRNT) and mouse protection assay with lethal doses of DENV-2, we identified four serotype-specific mAbs that had high neutralizing activity against DENV-2 infection. Of the four, E-DIII targeting mAb DB32-6 was the strongest neutralizing mAb against diverse DENV-2 strains. Using phage display and virus-like particles (VLPs) we found that residue K310 in the E-DIII A-strand was key to mAb DB32-6 binding E-DIII. We successfully converted DB32-6 to a humanized version that retained potency for the neutralization of DENV-2 and did not enhance the viral infection. The DB32-6 showed therapeutic efficacy against mortality induced by different strains of DENV-2 in two mouse models even in post-exposure trials. We used novel epi...Continue Reading

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Citations

Jan 12, 2013·Applied Microbiology and Biotechnology·Yao-Shen ChenTsung-Hsien Chang
Mar 8, 2013·Applied Microbiology and Biotechnology·Xiao-Feng LiCheng-Feng Qin
Nov 28, 2015·International Journal of Molecular Sciences·Yin-Liang TangHan-Chung Wu
Jan 21, 2016·Journal of Biomedical Science·Chien-Hsun WuHan-Chung Wu
Mar 31, 2015·Applied Microbiology and Biotechnology·Yayan LuoLifang Jiang
Jul 17, 2014·The Journal of Infectious Diseases·Yogy SimanjuntakYi-Ling Lin
Jan 5, 2014·PLoS Neglected Tropical Diseases·Petra EmmerichHerbert Schmitz
Aug 29, 2014·Journal of Virology·Maria ViskovskaB V Venkataram Prasad
Jul 3, 2015·PLoS Neglected Tropical Diseases·Chung-Tao TangHan-Chung Wu
Oct 16, 2013·Current Opinion in Infectious Diseases·Catherine H RobertsGavin Screaton
Jul 12, 2013·Advanced Healthcare Materials·Hsi-Kai WangChao-Min Cheng
Feb 27, 2014·Biotechnology & Genetic Engineering Reviews·Yaghoub SafdariMasoumeh Khalili

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Datasets Mentioned

BETA
DI084180
PM33974

Methods Mentioned

BETA
ELISA
affinity purification
flow cytometry
phage display
PCR
surface plasmon resonance
chip
Dissection
fluorescence microscopy

Software Mentioned

BIAevaluation

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