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Title | Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody. |
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Journal, issue, pages | Elife, Vol. 7, Year 2018 |
Publish date | Oct 18, 2018 |
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 / |
PubMed 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 ...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. |
External links | Elife / PubMed:30334522 / PubMed Central |
Methods | EM (single particle) |
Resolution | 13.0 Å |
Structure data | EMDB-6926: |