Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody
- National Chung-Hsing University, Taiwan, Republic of China
- Academia Sinica, Taiwan, Republic of China
- Centers for Disease Control and Prevention, United States
- National Cheng Kung University, Taiwan, Republic of China
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 ~31nm forming the major population under cryo-electron microscopy examination. Furthermore, mD2VLP particles of 31nm 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.
Data availability
The cryo-EM density map of mD2VLP has been deposited to Electron Microscopy Data Bank under accession number EMDB6926. All data generated or analyzed during this study are included in the manuscript and supporting files.
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Funding
Ministry of Science and Technology, Taiwan (104-2320-B-006-027)
- Shang-Rung Wu
Ministry of Science and Technology, Taiwan (105-2320-B-006-017-MY3)
- Shang-Rung Wu
Ministry of Science and Technology, Taiwan (104-2633-B-005-001)
- Day-Yu Chao
Ministry of Science and Technology, Taiwan (MOST 106-2313-B-005-029)
- Jyung-Hurng Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was carried out in compliance with the guidelines for the care and use of laboratory animals of the National Laboratory Animal Center, Taiwan. The animal use protocol has been reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of National Chung Hsing University (Approval Number: 101-58). All efforts were made to minimize suffering of mice.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody
eLife 7:e38970.
https://doi.org/10.7554/eLife.38970
