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標題: Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody
作者: Shen, Wen-Fan
Galula, Jedhan Ucat
Liu, Jyung-Hurng
Liao, Mei-Ying
Huang, Cheng-Hao
Wang, Yu-Chun
Wu, Han-Chung
Liang, Jian-Jong
Lin, Yi-Ling
Whitney, Matthew T
Chang, Gwong-Jen J
Chen, Sheng-Ren
Wu, Shang-Rung
Chao, Day-Yu
關鍵字: broad antibody response;cryoEM;dengue;infectious disease;microbiology;molecular biophysics;mouse;structural biology;vaccine;virus;virus-like particle;Amino Acid Sequence;Animals;Antibodies, Monoclonal;Antibodies, Neutralizing;Dengue Vaccines;Dengue Virus;Epitopes;Female;Immunization;Mice, Inbred BALB C;Serotyping;Solvents;Survival Analysis;Vaccines, Virus-Like Particle;Viral Envelope Proteins;Virion
Project: eLife, Volume 7
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.
DOI: 10.7554/eLife.38970
Appears in Collections:微生物暨公共衛生學研究所

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