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An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus

Authors :
Chang Hao Huang
Yi-Ling Lin
Han-Chung Wu
Matthew T. Whitney
Wen Fan Shen
Yu Chun Wang
Shang Rung Wu
Jyung-Hurng Liu
Gwong Jen J. Chang
Jian Jong Liang
Day-Yu Chao
Jedhan Ucat Galula
Sheng Ren Chen
Mei Ying Liao
Publication Year :
2018
Publisher :
Cold Spring Harbor Laboratory, 2018.

Abstract

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....cf1d8c494a43f617d4ab07f4b8b9a19f
Full Text :
https://doi.org/10.1101/351700