RT Journal Article
SR Electronic
T1 An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 351700
DO 10.1101/351700
A1 Wen-Fan Shen
A1 Jedhan Ucat Galula
A1 Jyung-Hurng Liu
A1 Mei-Ying Liao
A1 Chang-Hao Huang
A1 Yu-Chun Wang
A1 Han-Chung Wu
A1 Jian-Jong Liang
A1 Yi-Ling Lin
A1 Matthew T. Whitney
A1 Gwong-Jen J. Chang
A1 Sheng-Ren Chen
A1 Shang-Rung Wu
A1 Day-Yu Chao
YR 2018
UL http://biorxiv.org/content/early/2018/06/20/351700.abstract
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.