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Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody.
- Source :
-
ELife [Elife] 2018 Oct 18; Vol. 7. Date of Electronic Publication: 2018 Oct 18. - Publication Year :
- 2018
-
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.<br />Competing Interests: WS, JG, JL, ML, CH, YW, HW, JL, YL, MW, GC, SC, SW, DC No competing interests declared
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal immunology
Dengue Virus classification
Dengue Virus ultrastructure
Epitopes chemistry
Female
Immunization
Mice, Inbred BALB C
Serotyping
Solvents
Survival Analysis
Vaccines, Virus-Like Particle ultrastructure
Viral Envelope Proteins chemistry
Viral Envelope Proteins metabolism
Virion metabolism
Virion ultrastructure
Antibodies, Neutralizing immunology
Dengue Vaccines immunology
Dengue Virus immunology
Epitopes immunology
Vaccines, Virus-Like Particle immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 30334522
- Full Text :
- https://doi.org/10.7554/eLife.38970