In:
eLife, eLife Sciences Publications, Ltd, Vol. 7 ( 2018-10-18)
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 VLP derived from DENV serotype-2 were engineered becoming highly matured (mD2VLP) and showed variable size distribution with diameter of ~31 nm forming the major population under cryo-electron microscopy examination. Furthermore, mD2VLP particles of 31 nm diameter 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. Mice vaccinated with mD2VLP generated higher cross-reactive (CR) neutralization antibodies (NtAbs) and were fully protected against all 4 serotypes of DENV. Our results highlight the potential of ‘epitope-resurfaced’ mature-form D2VLPs in inducing quaternary structure-recognizing broad CR NtAbs to guide future dengue vaccine design.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.38970.001
DOI:
10.7554/eLife.38970.002
DOI:
10.7554/eLife.38970.003
DOI:
10.7554/eLife.38970.004
DOI:
10.7554/eLife.38970.005
DOI:
10.7554/eLife.38970.006
DOI:
10.7554/eLife.38970.007
DOI:
10.7554/eLife.38970.008
DOI:
10.7554/eLife.38970.009
DOI:
10.7554/eLife.38970.010
DOI:
10.7554/eLife.38970.011
DOI:
10.7554/eLife.38970.012
DOI:
10.7554/eLife.38970.013
DOI:
10.7554/eLife.38970.014
DOI:
10.7554/eLife.38970.015
DOI:
10.7554/eLife.38970.020
DOI:
10.7554/eLife.38970.016
DOI:
10.7554/eLife.38970.017
DOI:
10.7554/eLife.38970.018
DOI:
10.7554/eLife.38970.019
DOI:
10.7554/eLife.38970.021
DOI:
10.7554/eLife.38970.025
DOI:
10.7554/eLife.38970.022
DOI:
10.7554/eLife.38970.023
DOI:
10.7554/eLife.38970.024
DOI:
10.7554/eLife.38970.026
DOI:
10.7554/eLife.38970.027
DOI:
10.7554/eLife.38970.028
DOI:
10.7554/eLife.38970.029
DOI:
10.7554/eLife.38970.033
DOI:
10.7554/eLife.38970.034
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2018
detail.hit.zdb_id:
2687154-3