| Autor: |
Chang Hao Huang, Yi-Ling Lin, Han-Chung Wu, Matthew T. Whitney, Wen Fan Shen, Yu Chun Wang, Shang Rung Wu, Jyung-Hurng Liu, Gwong Jen J. Chang, Jian Jong Liang, Day-Yu Chao, Jedhan Ucat Galula, Sheng Ren Chen, Mei Ying Liao |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| DOI: |
10.1101/351700 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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