Epitope Resurfacing on Dengue Virus-like Particle Vaccine Preparation to Induce Broad Neutralizing Antibody

Overview

Journal Elife

Specialty Biology

Date 2018 Oct 19

PMID 30334522

Citations 17

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Octahedral small virus-like particles of dengue virus type 2.

Johnson A, Dodes Traian M, Walsh Jr R, Jenni S, Harrison S J Virol. 2025; 99(2):e0180924.

PMID: 39745459 PMC: 11853069. DOI: 10.1128/jvi.01809-24.

Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus.

Salem G, Galula J, Wu S, Liu J, Chen Y, Wang W Commun Biol. 2024; 7(1):15.

PMID: 38267569 PMC: 10808242. DOI: 10.1038/s42003-023-05661-w.

Lambda-free light chain: A serum marker of dengue disease via NS3 protease-mediated antibody cleavage.

Wang S, Kuo B, Ho T, Wan S, Yen K, Huang P Virulence. 2023; 14(1):2279355.

PMID: 37927064 PMC: 10766417. DOI: 10.1080/21505594.2023.2279355.

A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures.

Kuhn R, Barrett A, DeSilva A, Harris E, Kramer L, Montgomery R J Infect Dis. 2023; 228(Suppl 6):S398-S413.

PMID: 37849402 PMC: 10582523. DOI: 10.1093/infdis/jiad193.

N-linked glycosylation of flavivirus E protein contributes to viral particle formation.

Ishida K, Yagi H, Kato Y, Morita E PLoS Pathog. 2023; 19(10):e1011681.

PMID: 37819933 PMC: 10593244. DOI: 10.1371/journal.ppat.1011681.

References

Zhang S, Tan H, Hanson B, Ooi E . A simple method for Alexa Fluor dye labelling of dengue virus. J Virol Methods. 2010; 167(2):172-7. DOI: 10.1016/j.jviromet.2010.04.001. View

Fibriansah G, Ibarra K, Ng T, Smith S, Tan J, Lim X . DENGUE VIRUS. Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers. Science. 2015; 349(6243):88-91. PMC: 4672004. DOI: 10.1126/science.aaa8651. View

Katzelnick L, Coloma J, Harris E . Dengue: knowledge gaps, unmet needs, and research priorities. Lancet Infect Dis. 2017; 17(3):e88-e100. PMC: 5967882. DOI: 10.1016/S1473-3099(16)30473-X. View

Cherrier M, Kaufmann B, Nybakken G, Lok S, Warren J, Chen B . Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody. EMBO J. 2009; 28(20):3269-76. PMC: 2771083. DOI: 10.1038/emboj.2009.245. View

Chang G, HUNT A, Davis B . A single intramuscular injection of recombinant plasmid DNA induces protective immunity and prevents Japanese encephalitis in mice. J Virol. 2001; 74(9):4244-52. PMC: 111940. DOI: 10.1128/jvi.74.9.4244-4252.2000. View

Lok S, Kostyuchenko V, Nybakken G, Holdaway H, Battisti A, Sukupolvi-Petty S . Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol. 2008; 15(3):312-7. DOI: 10.1038/nsmb.1382. View

Halstead S . Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age. Vaccine. 2017; 35(47):6355-6358. DOI: 10.1016/j.vaccine.2017.09.089. View

Pierson T, Fremont D, Kuhn R, Diamond M . Structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development. Cell Host Microbe. 2008; 4(3):229-38. PMC: 2678546. DOI: 10.1016/j.chom.2008.08.004. View

Zhang X, Ge P, Yu X, Brannan J, Bi G, Zhang Q . Cryo-EM structure of the mature dengue virus at 3.5-Å resolution. Nat Struct Mol Biol. 2012; 20(1):105-10. PMC: 3593067. DOI: 10.1038/nsmb.2463. View

10.

Rey F, Stiasny K, Vaney M, Dellarole M, Heinz F . The bright and the dark side of human antibody responses to flaviviruses: lessons for vaccine design. EMBO Rep. 2017; 19(2):206-224. PMC: 5797954. DOI: 10.15252/embr.201745302. View

11.

Rodenhuis-Zybert I, van der Schaar H, da Silva Voorham J, van der Ende-Metselaar H, Lei H, Wilschut J . Immature dengue virus: a veiled pathogen?. PLoS Pathog. 2010; 6(1):e1000718. PMC: 2798752. DOI: 10.1371/journal.ppat.1000718. View

12.

Allison S, Stadler K, Mandl C, Kunz C, Heinz F . Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form. J Virol. 1995; 69(9):5816-20. PMC: 189449. DOI: 10.1128/JVI.69.9.5816-5820.1995. View

13.

Nelson S, Jost C, Xu Q, Ess J, Martin J, Oliphant T . Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization. PLoS Pathog. 2008; 4(5):e1000060. PMC: 2330159. DOI: 10.1371/journal.ppat.1000060. View

14.

Fibriansah G, Tan J, Smith S, de Alwis R, Ng T, Kostyuchenko V . A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins. Nat Commun. 2015; 6:6341. PMC: 4346626. DOI: 10.1038/ncomms7341. View

15.

Guy B, Jackson N . Dengue vaccine: hypotheses to understand CYD-TDV-induced protection. Nat Rev Microbiol. 2015; 14(1):45-54. DOI: 10.1038/nrmicro.2015.2. View

16.

Crowe Jr J . Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design. Cell Host Microbe. 2017; 22(2):193-206. PMC: 5700460. DOI: 10.1016/j.chom.2017.07.013. View

17.

Metz S, Thomas A, White L, Stoops M, Corten M, Hannemann H . Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope. Virol J. 2018; 15(1):60. PMC: 5879749. DOI: 10.1186/s12985-018-0970-2. View

18.

Kirkpatrick B, Whitehead S, Pierce K, Tibery C, Grier P, Hynes N . The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Sci Transl Med. 2016; 8(330):330ra36. DOI: 10.1126/scitranslmed.aaf1517. View

19.

Henein S, Swanstrom J, Byers A, Moser J, Shaik S, Bonaparte M . Dissecting Antibodies Induced by a Chimeric Yellow Fever-Dengue, Live-Attenuated, Tetravalent Dengue Vaccine (CYD-TDV) in Naive and Dengue-Exposed Individuals. J Infect Dis. 2016; 215(3):351-358. PMC: 6392503. DOI: 10.1093/infdis/jiw576. View

20.

Dejnirattisai W, Wongwiwat W, Supasa S, Zhang X, Dai X, Rouvinski A . A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus. Nat Immunol. 2014; 16(2):170-177. PMC: 4445969. DOI: 10.1038/ni.3058. View