Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody.
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| 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.
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| Authors | Wen-Fan Shen, Jedhan Ucat Galula, Jyung-Hurng Liu, Mei-Ying Liao, Cheng-Hao Huang, Yu-Chun Wang, Han-Chung Wu, Jian-Jong Liang, Yi-Ling Lin, Matthew T Whitney, Gwong-Jen J Chang, Sheng-Ren Chen, Shang-Rung Wu, Day-Yu Chao |
| Journal | eLife (Elife) Vol. 7 (10 18 2018) ISSN: 2050-084X [Electronic] England |
| PMID | 30334522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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