A novel platform for virus-like particle-display of flaviviral envelope domain III: induction of Dengue and West Nile virus neutralizing antibodies
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- 作者：Anthony JS Chua (1) (2)
Cyrielle Vituret (3) (4)
Melvin LC Tan (1)
Ga?lle Gonzalez (3) (4)
Pierre Boulanger (3)
Mah-Lee Ng (1) (2) (5)
Saw-See Hong (3) (4) (6) - 关键词：Flavivirus envelope glycoprotein ; Domain III ; Retroviral Gag ; Virus ; like particles (VLPs) ; Pseudotyping ; VLP ; display ; CD16/Fc?RIγ chimera ; Recombinant baculovirus
- 刊名：Virology Journal
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：10
- 期：1
- 全文大小：1768KB
- 参考文献：1. Cox MM: Progress on baculovirus-derived influenza vaccines. / Curr Opin Mol Ther 2008, 10:56-1.
2. Schiller JT, Castellsagué X, Villa LL, Hildesheim A: An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. / Vaccine 2008, 26, Suppl. 10:K53-K61. 10.1016/j.vaccine.2008.06.002">CrossRef
3. Schiller JT, Nardelli-Haefliger D: Second generation HPV vaccines to prevent cervical cancer. / Vaccine 2006, 24, Suppl. 3:147-53. 10.1016/j.vaccine.2006.05.123">CrossRef
4. Wang CY, Miyazaki N, Yamashita T, Higashiura A, Nakagawa A, Li TC, Takeda N, Xing L, Hjalmarsson E, Friberg C: Crystallization and preliminary X-ray diffraction analysis of recombinant hepatitis E virus-like particle. / Acta Crystallogr Sect F Struct Biol Cryst Commun 2008, 64:318-22. 10.1107/S1744309108007197">CrossRef
5. Spohn G, Jennings GT, Martina BE, Keller I, Beck M, Pumpens P, Osterhaus AD, Bachmann MF: A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice. / Virol J 2010, 7:146. 10.1186/1743-422X-7-146">CrossRef
6. Patient R, Hourioux C, Roingeard P: Morphogenesis of hepatitis B virus and its subviral envelope particles. / Cell Microbiol 2009, 11:1561-570. 10.1111/j.1462-5822.2009.01363.x">CrossRef
7. Patient R, Hourioux C, Vaudin P, Pagès JC, Roingeard P: Chimeric hepatitis B and C viruses envelope proteins can form subviral particles: implications for the design of new vaccine strategies. / New Biotechnol 2009, 25:226-34. 10.1016/j.nbt.2009.01.001">CrossRef
8. Krammer F, Nakowitsch S, Messner P, Palmberger D, Ferko B, Grabherr R: Swine-origin pandemic H1N1 influenza virus-like particles produced in insect cells induce hemagglutination inhibiting antibodies in BALB/c mice. / Biotechnol J 2010, 5:17-3. 10.1002/biot.200900267">CrossRef
9. Adamson CS, Freed EO: Human immunodeficiency virus type 1 assembly, release and maturation. / Adv Pharmacol 2007, 55:347-87. 10.1016/S1054-3589(07)55010-6">CrossRef
10. Boulanger P, Jones I: Morphogenesis and maturation of Retroviruses. Use of heterologous expression systems to study retroviral morphogenesis. In / Curr Topics Microbiol Immunol, Volume 214. Edited by: Kr?usslich H-G. Berlin, Heidelberg, New York: Springer; 1996:237-60.
11. Carrière C, Gay B, Chazal N, Morin N, Boulanger P: Sequence requirement for encapsidation of deletion mutants and chimeras of human immunodeficiency virus type 1 Gag precursor into retrovirus-like particles. / J Virol 1995, 69:2366-377.
12. Gay B, Tournier J, Chazal N, Carrière C, Boulanger P: Morphopoietic determinants of HIV-1 GAG particles assembled in baculovirus-infected cells. / Virology 1998, 247:160-69. 10.1006/viro.1998.9237">CrossRef
13. Royer M, Cerutti M, Gay B, Hong SS, Devauchelle G, Boulanger P: Functional domains of HIV-1 gag -polyprotein expressed in baculovirus-infected cells. / Virology 1991, 184:417-22. 10.1016/0042-6822(91)90861-5">CrossRef
14. Royer M, Hong SS, Gay B, Cerutti M, Boulanger P: Expression and extracellular release of human immunodeficiency virus type 1 Gag precursors by recombinant baculovirus-infected cells. / J Virol 1992, 66:3230-235.
15. Wilk T, Gross I, Gowen BE, Rutten T, de Haas F, Welker R, Kr?usslich H-G, Boulanger P, Fuller SD: Organization of immature human immunodeficiency virus type 1. / J Virol 2001, 75:759-71. 10.1128/JVI.75.2.759-771.2001">CrossRef
16. Chazal N, Gerlier D: Virus entry, assembly, budding and membrane rafts. / Microbiol Molec Biol Rev 2003, 67:226-37. 10.1128/MMBR.67.2.226-237.2003">CrossRef
17. Granio O, Porcherot M, Corjon S, Kitidee K, Henning P, Eljaafari A, Cimarelli A, Lindholm L, Miossec P, Boulanger P, Hong SS: Improved adenovirus type 5 vector-mediated transduction of resistant cells by piggybacking on coxsackie B-adenovirus receptor-pseudotyped baculovirus. / J Virol 2009, 83:6048-066. 10.1128/JVI.00012-09">CrossRef
18. Hsu M, Zhang J, Flint M, Logvinoff C, Cheng-Mayer C, Rice CM, McKeating JA: Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. / Proc Natl Acad Sci USA 2003, 100:7271-276. 10.1073/pnas.0832180100">CrossRef
19. Johnson LG, Olsen JC, Naldini L, Boucher RC: Pseudotyped human lentiviral vector-mediated gene transfer to airway epithelia in vivo. / Gene Ther 2000, 7:568-74. 10.1038/sj.gt.3301138">CrossRef
20. Matsuura Y, Tani H, Suzuki K, Kimura-Someya T, Suzuki R, Aizaki H, Ishii K, Moriishi K, Robison CS, Whitt MA, Miyamura T: Characterization of pseudotype VSV possessing HCV envelope proteins. / Virology 2005, 286:263-75. 10.1006/viro.2001.0971">CrossRef
21. Sandrin V, Boulanger P, Penin F, Granier C, Cosset FL, Bartosch B: Assembly of functional hepatitis C virus glycoproteins on infectious pseudoparticles occurs intracellularly and requires concomitant incorporation of E1 and E2 glycoproteins. / J Gen Virol 2005, 86:3189-199. 10.1099/vir.0.81428-0">CrossRef
22. Sandrin V, Muriaux D, Darlix J-L, Cosset F-L: Intracellular trafficking of Gag and Env proteins and their interactions modulate pseudotyping of retroviruses. / J Virol 2004, 78:7153-164. 10.1128/JVI.78.13.7153-7164.2004">CrossRef
23. Deml L, Speth C, Dierich MP, Wolf H, Wagner R: Recombinant HIV-1 Pr55gag virus-like particles: potent stimulators of innate and acquired immune responses. / Mol Immunol 2005, 42:259-77. 10.1016/j.molimm.2004.06.028">CrossRef
24. Crill WD, Chang GJ: Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes. / J Virol 2004, 78:13975-3986. 10.1128/JVI.78.24.13975-13986.2004">CrossRef
25. Crill WD, Roehrig JT: Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. / J Virol 2001, 75:7769-773. 10.1128/JVI.75.16.7769-7773.2001">CrossRef
26. Bernardo L, Izquierdo A, Alvarez M, Rosario D, Prado I, López C, Martínez R, Castro J, Santana E, Hermida L: Immunogenicity and protective efficacy of a recombinant fusion protein containing the domain III of the dengue 1 envelope protein in non-human primates. / Antiviral Res 2008, 80:194-99. 10.1016/j.antiviral.2008.06.005">CrossRef
27. Chen YC, Huang HN, Lin CT, Chen YF, King CC, Wu HC: Generation and characterization of monoclonal antibodies against dengue virus type 1 for epitope mapping and serological detection by epitope-based peptide antigens. / Clin Vaccine Immunol 2007, 14:404-11. 10.1128/CVI.00249-06">CrossRef
28. Chin JF, Chu JJ, Ng ML: The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry. / Microbes Infect 2007, 9:1-. 10.1016/j.micinf.2006.09.009">CrossRef
29. Chu JH, Chiang CC, Ng ML: Immunization of flavivirus West Nile recombinant envelope domain III protein induced specific immune response and protection against West Nile virus infection. / J Immunol 2007, 178:2699-705.
30. Chu JJ, Leong PW, Ng ML: Analysis of the endocytic pathway mediating the infectious entry of mosquito-borne flavivirus West Nile into Aedes albopictus mosquito (C6/36) cells. / Virology 2006, 349:463-75. 10.1016/j.virol.2006.01.022">CrossRef
31. Chu JJ, Rajamanonmani R, Li J, Bhuvanakantham R, Lescar J, Ng ML: Inhibition of West Nile virus entry by using a recombinant domain III from the envelope glycoprotein. / J Gen Virol 2005, 86:405-12. 10.1099/vir.0.80411-0">CrossRef
32. Etemad B, Batra G, Raut R, Dahiya S, Khanam S, Swaminathan S, Khanna N: An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes. / AmJTrop Med Hyg 2008, 79:353-63.
33. Izquierdo A, Bernardo L, Martin J, Santana E, Hermida L, Guillén G, Guzmán MG: Serotype-specificity of recombinant fusion proteins containing domain III of dengue virus. / Virus Res 2008, 138:135-38. 10.1016/j.virusres.2008.08.008">CrossRef
34. Leng CH, Liu SJ, Tsai JP, Li YS, Chen MY, Liu HH, Lien SP AY, Hsiao KN, Lai LW: A novel dengue vaccine candidate that induces cross-neutralizing antibodies and memory immunity. / Microbes Infect 2009, 11:288-95. 10.1016/j.micinf.2008.12.004">CrossRef
35. Li L, Barrett AD, Beasley DW: Differential expression of domain III neutralizing epitopes on the envelope proteins of West Nile virus strains. / Virology 2005, 335:99-05. 10.1016/j.virol.2005.02.011">CrossRef
36. Marcos E, Gil L, Lazo L, Izquierdo A, Brown E, Suzarte E, Valdés I, García A, Méndez L, Guzmán MG: Purified and highly aggregated chimeric protein DIIIC-2 induces a functional immune response in mice against dengue 2 virus. / Arch Virol 2013, 158:225-30. 10.1007/s00705-012-1471-z">CrossRef
37. Beasley DW, Barrett AD: Identification of neutralizing epitopes within structural domain III of the West Nile virus envelope protein. / J Virol 2002, 76:13097-3100. 10.1128/JVI.76.24.13097-13100.2002">CrossRef
38. Clémenceau B, Congy-Jolivet N, Gallot G, Vivien R, Gaschet J, Thibault G, Vié H: Antibody-dependent cellular cytotoxicity (ADCC) is mediated by genetically modified antigen-specific human T lymphocytes. / Blood 2006, 107:4669-677. 10.1182/blood-2005-09-3775">CrossRef
39. Moretta L: Dissecting CD56dim human NK cells. / Blood 2010, 116:3689-691. 10.1182/blood-2010-09-303057">CrossRef
40. Freed EO: HIV-1 and the host cell: an intimate association. / Trends Microbiol 2004, 12:170-77. 10.1016/j.tim.2004.02.001">CrossRef
41. Hong SS, Boulanger P: Self-assembly-defective dominant mutants of HIV-1 Gag phenotypically expressed in baculovirus-infected cells. / J Virol 1993, 67:2787-798.
42. Chazal N, Carrière C, Gay B, Boulanger P: Phenotypic characterization of insertion mutants of the human immunodeficiency virus type 1 Gag precursor expressed in recombinant baculovirus-infected cells. / J Virol 1994, 68:111-22.
43. Chazal N, Gay B, Carrière C, Tournier J, Boulanger P: Human immunodeficiency virus type 1 MAp17 deletion mutants expressed in baculovirus-infected cells: cis and trans effects on the Gag precursor assembly pathway. / J Virol 1995, 69:365-75.
44. DaFonseca S, Blommaert A, Coric P, Hong SS, Bouaziz S, Boulanger P: The 3-O-(3-3-dimethylsuccinyl) derivative of betulinic acid (DSB) inhibits the assembly of virus-like particles in HIV-1 Gag precursor-expressing cells. / Antiviral Ther 2007, 12:1185-203.
45. Royer M, Bardy M, Gay B, Tournier J, Boulanger P: Proteolytic activity in vivo and encapsidation of recombinant HIV-1 proteinase expressed in baculovirus-infected cells. / J Gen Virol 1997, 78:131-42.
46. Bardy M, Gay B, Pébernard S, Chazal N, Courcoul M, Vigne R, Decroly E, Boulanger P: Interaction of human immunodeficiency virus type 1 Vif with Gag and Gag-Pol precursors: co-encapsidation and interference with viral protease-mediated Gag processing. / J Gen Virol 2001, 82:2719-733.
47. DaFonseca S, Coric P, Gay B, Hong SS, Bouaziz S, Boulanger P: The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3-3-dimethylsuccinyl) betulinic acid (DSB) is counteracted by Vif and requires its Zinc-binding domain. / Virol J 2008, 5:162. 10.1186/1743-422X-5-162">CrossRef
48. Westaway EG: Assessment and application of a cell line from pig kidney for plaque assay and neutralization tests with 12 group B arboviruses. / Am J Epidemiol 1966, 84:439-56.
49. Huvent I, Hong SS, Fournier C, Gay B, Tournier J, Carriere C, Courcoul M, Vigne R, Spire B, Boulanger P: Interaction and co-encapsidation of HIV-1 Vif and Gag recombinant proteins. / J Gen Virol 1998, 79:1069-081.
50. Briggs JA, Johnson MC, Simon MN, Fuller SD, Vogt VM: Cryo-electron microscopy reveals conserved and divergent features of gag packing in immature particles of Rous sarcoma virus and human immunodeficiency virus. / J Mol Biol 2006, 355:157-68. 10.1016/j.jmb.2005.10.025">CrossRef
51. Briggs JA, Riches JD, Glass B, Bartonova V, Zanetti G, Kr?usslich HG: Structure and assembly of immature HIV. / Proc Natl Acad Sci USA 2009, 106:11090-1095. 10.1073/pnas.0903535106">CrossRef
52. Briggs JA, Simon MN, Gross I, Kr?usslich H-G, Fuller SD, Vogt VM, Johnson MC: The stoichiometry of Gag protein in HIV-1. / Nat Struct Mol Biol 2004, 11:672-75. 10.1038/nsmb785">CrossRef
53. Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, Sundquist WI, Hill CP, Yeager M: X-ray structures of the hexameric building block of the HIV capsid. / Cell 2009, 137:1282-292. 10.1016/j.cell.2009.04.063">CrossRef
54. Chertova E, Chertov O, Coren LV, Roser JD, Trubey CM, Bess JWJ, Sowder RC, Barsov E, Hood BL, Fisher RJ: Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages. / J Virol 2006, 80:9039-052. 10.1128/JVI.01013-06">CrossRef
55. Lee JW, Chu JJ, Ng ML: Quantifying the specific binding between West Nile virus envelope domain III protein and the cellular receptor alphaVbeta3 integrin. / J Biol Chem 2006, 281:1352-360. 10.1074/jbc.M506614200">CrossRef
56. Chua JJ, Bhuvanakantham R, Chow VT, Ng ML: Recombinant non-structural 1 (NS1) protein of dengue-2 virus interacts with human STAT3beta protein. / Virus Res 2005, 112:85-4. 10.1016/j.virusres.2005.03.025">CrossRef
57. Dunn MD, Rossi SL, Carter DM, Vogt MR, Mehlhop E, Diamond MS, Ross TM: Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice. / Virol J 2010, 7:95. 10.1186/1743-422X-7-95">CrossRef
58. Bahuon C, Desprès P, Pardigon N, Panthier JJ, Cordonnier N, Lowenski S, Richardson J, Zientara S, Lecollinet S: IS-98-ST1 West Nile virus derived from an infectious cDNA clone retains neuroinvasiveness and neurovirulence properties of the original virus. / PLoS One 2012, 7:e47666. 10.1371/journal.pone.0047666">CrossRef
59. Lanciotti RS: Molecular amplification assays for the detection of flaviviruses. / Adv Virus Res 2003, 61:67-9. 10.1016/S0065-3527(03)61002-X">CrossRef
60. Kaufmann B, Vogt MR, Goudsmit J, Holdaway HA, Aksyuk AA, Chipman PR, Kuhn RJ, Diamond MS, Rossmann MG: Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354. / Proc Natl Acad Sci USA 2010, 107:18950-8955. 10.1073/pnas.1011036107">CrossRef
61. Muriaux D, Mirro J, Harvin D, Rein A: RNA is a structural element in retrovirus particles. / Proc Natl Acad Sci USA 2001, 98:5246-251. 10.1073/pnas.091000398">CrossRef
62. Freed EO, Martin MA: Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions. / J Virol 1996, 70:341-51.
63. Miller RK, Qadota H, Stark TJ, Mercer KB, Wortham TS, Anyanful A, Benian GM: CSN-5, a component of the COP9 signalosome complex, regulates the levels of UNC-96 and UNC-98, two components of M-lines in Caenorhabditis elegans muscle. / Mol Biol Cell 2009, 20:3608-616. 10.1091/mbc.E09-03-0208">CrossRef
64. Kaufmann B, Chipman PR, Holdaway HA, Johnson S, Fremont DH, Kuhn RJ, Diamond MS, Rossmann MG: Capturing a Flavivirus Pre-Fusion Intermediate. / PLoS Pathog 2010, 5:e1000672. 10.1371/journal.ppat.1000672">CrossRef
65. Dowd KA, Jost CA, Durbin AP, Whitehead SS, Pierson TC: A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. / PLoS Pathog 2011, 7:e1002111. 10.1371/journal.ppat.1002111">CrossRef
66. Mukhopadhyay S, Kim BS, Chipman PR, Rossman MG, Kuhn RJ: Structure of West Nile virus. / Science 2003, 302:248. 10.1126/science.1089316">CrossRef
67. Zhang W, Chipman PR, Corver J, Johnson PR, Zhang Y, Mukhopadhyay S, Baker TS, Strauss JH, Rossmann MG, Kuhn RJ: Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. / Nat Struct Biol 2003, 10:907-12. 10.1038/nsb990">CrossRef
68. Ludolfs D, Niedrig M, Paweska JT, Schmitz H: Reverse ELISA for the detection of anti West Nile virus IgG antibodies in humans. / Eur J Clin Microbiol Infect Dis 2007, 26:467-73. 10.1007/s10096-007-0309-1">CrossRef
69. Oliphant T, Engle M, Nybakken GE, Doane C, Johnson S, Huang L, Gorlatov S, Mehlhop E, Marri A, Chung KM: Development of a humanized monoclonal antibody with therapeutic potential against West Nile virus. / Nat Med 2005, 11:522-30. 10.1038/nm1240">CrossRef
70. Pattnaik P, Babu JP, Verma SK, Tak V, Rao PV: Bacterially expressed and refolded envelope protein (domain III) of dengue virus type-4 binds heparan sulfate. / J Chromatogr B Analyt Technol Biomed Life Sci 2007, 846:184-94. 10.1016/j.jchromb.2006.08.051">CrossRef
71. Tripathi NK, Babu JP, Shrivastva A, Parida M, Jana AM, Rao PVL: Production and characterization of recombinant dengue virus type 4 serotype envelope domain III protein. / J Biotechnol 2008, 134:278-86. 10.1016/j.jbiotec.2008.02.001">CrossRef
72. Tripathi NK, Shrivastva A, Pattnaik P, Parida M, Dash PK, Jana AM, Rao PVL: Production, purification and characterization of recombinant dengue multiepitope protein. / Biotechnol Appl Biochem 2007, 46:105-13. 10.1042/BA20060090">CrossRef
73. Throsby M, Ter Meulen J, Geuijen C, Goudsmit J, de Kruif J: Mapping and analysis of West Nile virus-specific monoclonal antibodies: prospects for vaccine development. / Expert Rev Vaccine 2007, 6:183-91. 10.1586/14760584.6.2.183">CrossRef
74. Dowd KA, Pierson TC: Antibody-mediated neutralization of flaviviruses: a reductionist view. / Virology 2011, 411:306-15. 10.1016/j.virol.2010.12.020">CrossRef
75. Cockburn JJ, Navarro Sanchez ME, Fretes N, Urvoas A, Staropoli I, Kikuti CM, Coffey LL, Arenzana Seisdedos F, Bedouelle H, Rey FA: Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. / Structure 2012, 20:303-14. 10.1016/j.str.2012.01.001">CrossRef - 作者单位：Anthony JS Chua (1) (2)
Cyrielle Vituret (3) (4)
Melvin LC Tan (1)
Ga?lle Gonzalez (3) (4)
Pierre Boulanger (3)
Mah-Lee Ng (1) (2) (5)
Saw-See Hong (3) (4) (6)
1. Flavivirology Laboratory, Department of Microbiology, National University of Singapore, 5 Science Drive 2, Singapore, 117597, Singapore
2. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore
3. University Lyon I & UMS-3444 Biosciences Gerland-Lyon Sud, 50, avenue Tony Garnier, Lyon, 69366, France
4. Retroviruses and Comparative Pathology, Université Lyon I & INRA UMR-754, 50, avenue Tony Garnier, Lyon Cedex 07, 69366, France
5. Flavivirology Laboratory, Department of Microbiology, National University Health System, 1E, Kent Ridge Road, Singapore, 119228, Singapore
6. Institut National de la Santé et de la Recherche Médicale, 101, rue de Tolbiac, Paris, 75013, France - ISSN：1743-422X
文摘
CD16-RIgE is a chimeric human membrane glycoprotein consisting of the CD16 ectodomain fused to the transmembrane domain and cytoplasmic tail of the gamma chain of the high affinity receptor of IgE (RIgE). Coexpression of CD16-RIgE and HIV-1 Pr55Gag polyprotein precursor (Pr55GagHIV) in insect cells resulted in the incorporation of CD16-RIgE glycoprotein into the envelope of extracellular virus-like particles (VLPs), a phenomenon known as pseudotyping. Taking advantage of this property, we replaced the CD16 ectodomain of CD16-RIgE by the envelope glycoprotein domain III (DIII) of dengue virus serotype 1 (DENV1) or West Nile virus Kunjin (WNVKun). The two resulting chimeric proteins, DIII-DENV1-RIgE and DIII-WNVKun-RIgE, were addressed to the plasma membrane, exposed at the surface of human and insect cells, and incorporated into extracellular VLPs when coexpressed with Pr55GagHIV in insect cells. The DIII domains were accessible at the surface of retroviral VLPs, as shown by their reactivity with specific antibodies, and notably antibodies from patient sera. The DIII-RIgE proteins were found to be incorporated in VLPs made of SIV, MLV, or chimeric MLV-HIV Gag precursors, indicating that DIII-RIgE could pseudotype a wide variety of retroviral VLPs. VLP-displayed DIII were capable of inducing specific neutralizing antibodies against DENV and WNV in mice. Although the neutralization response was modest, our data confirmed the capability of DIII to induce a flavivirus neutralization response, and suggested that our VLP-displayed CD16-RIgE-based platform could be developed as a vaccine vector against different flaviviruses and other viral pathogens.