Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody

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

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9 Citations (Scopus)

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.

Original languageEnglish
Article numbere38970
JournaleLife
Volume7
DOIs
Publication statusPublished - 2018 Oct

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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