PT  - JOURNAL ARTICLE
AU  - Wen-Fan Shen
AU  - Jedhan Ucat Galula
AU  - Jyung-Hurng Liu
AU  - Mei-Ying Liao
AU  - Chang-Hao Huang
AU  - Yu-Chun Wang
AU  - Han-Chung Wu
AU  - Jian-Jong Liang
AU  - Yi-Ling Lin
AU  - Matthew T. Whitney
AU  - Gwong-Jen J. Chang
AU  - Sheng-Ren Chen
AU  - Shang-Rung Wu
AU  - Day-Yu Chao
TI  - An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus
AID  - 10.1101/351700
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 351700
4099  - http://biorxiv.org/content/early/2018/06/20/351700.short
4100  - http://biorxiv.org/content/early/2018/06/20/351700.full
AB  - 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.