{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:44:23Z","timestamp":1783604663374,"version":"3.55.0"},"reference-count":121,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Flaviviruses include several medically important viruses, such as Zika virus (ZIKV), Dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). They have expanded in geographic distribution and refocused international attention in recent years. Vaccination is one of the most effective public health strategies for combating flavivirus infections. In this review, we summarized virus-like particle (VLP)-based vaccines against the above four mentioned flaviviruses. Potential strategies to improve the efficacy of VLP-based flavivirus vaccines were also illustrated. The applications of flavivirus VLPs as tools for viral detection and antiviral drug screening were finally proposed.<\/jats:p>","DOI":"10.3390\/vaccines8030481","type":"journal-article","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T08:05:18Z","timestamp":1598515518000},"page":"481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-1453","authenticated-orcid":false,"given":"Naru","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-7135","authenticated-orcid":false,"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Fudan University, Shanghai 200433, China"},{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Du","sequence":"additional","affiliation":[{"name":"Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jcv.2018.09.020","article-title":"CD4 T cell responses to flaviviruses","volume":"108","author":"Aberle","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Viennet, E., Frentiu, F.D., Williams, C.R., Mincham, G., Jansen, C.C., Montgomery, B.L., Flower, R.L.P., and Faddy, H.M. (2020). Estimation of mosquito-borne and sexual transmission of Zika virus in Australia: Risks to blood transfusion safety. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008438"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.htct.2018.01.011","article-title":"Risk of Zika virus transmission by blood donations in Brazil","volume":"40","author":"Magnus","year":"2018","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000446219","article-title":"West Nile virus in Europe and safety of blood transfusion","volume":"43","author":"Pisani","year":"2016","journal-title":"Transfus. Med. Hemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.15585\/mmwr.mm6508e2","article-title":"Transmission of Zika Virus Through Sexual Contact with Travelers to Areas of Ongoing Transmission-Continental United States, 2016","volume":"65","author":"Hills","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/QCO.0000000000000414","article-title":"Zika virus as a sexually transmitted pathogen","volume":"31","author":"Mead","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Holbrook, M.R. (2017). Historical Perspectives on Flavivirus Research. Viruses, 9.","DOI":"10.3390\/v9050097"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1038\/nm1144","article-title":"Emerging flaviviruses: The spread and resurgence of Japanese encephalitis, West Nile and dengue viruses","volume":"10","author":"Mackenzie","year":"2004","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0092-8674(02)00660-8","article-title":"Structure of dengue virus: Implications for flavivirus organization, maturation, and fusion","volume":"108","author":"Kuhn","year":"2002","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.mi.44.100190.003245","article-title":"Flavivirus genome organization, expression, and replication","volume":"44","author":"Chambers","year":"1990","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1128\/JVI.76.10.4773-4784.2002","article-title":"Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles","volume":"76","author":"Kummerer","year":"2002","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7804","DOI":"10.1128\/JVI.77.14.7804-7813.2003","article-title":"Molecular and functional analyses of Kunjin virus infectious cDNA clones demonstrate the essential roles for NS2A in virus assembly and for a nonconservative residue in NS3 in RNA replication","volume":"77","author":"Liu","year":"2003","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1128\/JVI.79.3.1343-1350.2005","article-title":"West Nile virus inhibits the signal transduction pathway of alpha interferon","volume":"79","author":"Guo","year":"2005","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14333","DOI":"10.1073\/pnas.2335168100","article-title":"Inhibition of interferon signaling by dengue virus","volume":"100","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nsmb.2463","article-title":"Cryo-EM structure of the mature dengue virus at 3.5-A resolution","volume":"20","author":"Zhang","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8475","DOI":"10.1128\/jvi.71.11.8475-8481.1997","article-title":"Proteolytic activation of tick-borne encephalitis virus by furin","volume":"71","author":"Stadler","year":"1997","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of the Zika virus envelope protein and its complex with a flavivirus broadly protective antibody","volume":"19","author":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11467","DOI":"10.1128\/JVI.01125-06","article-title":"Crystal structure of the West Nile virus envelope glycoprotein","volume":"80","author":"Nybakken","year":"2006","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1128\/JVI.06072-11","article-title":"Crystal structure of the Japanese encephalitis virus envelope protein","volume":"86","author":"Luca","year":"2012","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1128\/JVI.79.2.1223-1231.2005","article-title":"Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein","volume":"79","author":"Modis","year":"2005","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0140-6736(17)33106-9","article-title":"Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: Phase 1, randomised, double-blind, placebo-controlled clinical trials","volume":"391","author":"Modjarrad","year":"2018","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Stephenson, K.E., Tan, C.S., Walsh, S.R., Hale, A., Ansel, J.L., Kanjilal, D.G., Jaegle, K., Peter, L., Borducchi, E.N., and Nkolola, J.P. (2020). Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: A single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial. Lancet Infect. Dis., S1473\u2013S3099.","DOI":"10.1016\/S1473-3099(20)30085-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0140-6736(17)33105-7","article-title":"Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: Randomised, open-label, phase 1 clinical trials","volume":"391","author":"Gaudinski","year":"2018","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.3389\/fimmu.2020.01055","article-title":"Challenges in Dengue vaccines development: Pre-existing infections and cross-reactivity","volume":"11","author":"Izmirly","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1016\/j.vaccine.2017.08.066","article-title":"Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness","volume":"35","author":"Wichmann","year":"2017","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41467-017-00737-8","article-title":"A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage","volume":"8","author":"Shan","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11908-017-0566-9","article-title":"Live attenuated yellow fever 17D vaccine: A legacy vaccine still controlling outbreaks in modern day","volume":"19","author":"Collins","year":"2017","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1080\/21645515.2017.1414763","article-title":"Immunogenicity and safety of inactivated chromatographically purified Vero cell-derived Japanese encephalitis vaccine in Thai children","volume":"14","author":"Chanthavanich","year":"2018","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s12250-019-00090-8","article-title":"Electroporation-mediated immunization of a candidate DNA vaccine expressing dengue virus serotype 4 prM-E antigen confers long-term protection in mice","volume":"34","author":"Sheng","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6911","DOI":"10.1016\/j.vaccine.2018.10.022","article-title":"Amphiphilic block copolymer delivery of a DNA vaccine against Zika virus","volume":"36","author":"Hraber","year":"2018","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12360","DOI":"10.1038\/s41598-018-30258-3","article-title":"Oral delivery of a DNA vaccine expressing the PrM and E genes: A promising vaccine strategy against flavivirus in ducks","volume":"8","author":"Huang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e01485-18","DOI":"10.1128\/JVI.01485-18","article-title":"A measles virus-based vaccine candidate mediates protection against Zika virus in an allogeneic mouse pregnancy model","volume":"93","author":"Nurnberger","year":"2019","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1128\/CVI.00249-07","article-title":"Comparative efficacies of three commercially available vaccines against West Nile Virus (WNV) in a short-duration challenge trial involving an equine WNV encephalitis model","volume":"14","author":"Seino","year":"2007","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.vetimm.2008.02.002","article-title":"A West Nile virus (WNV) recombinant canarypox virus vaccine elicits WNV-specific neutralizing antibodies and cell-mediated immune responses in the horse","volume":"123","author":"Garch","year":"2008","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"420","DOI":"10.4269\/ajtmh.16-0293","article-title":"Plant-produced subunit vaccine candidates against yellow fever induce virus neutralizing antibodies and confer protection against viral challenge in animal models","volume":"98","author":"Tottey","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.ijbiomac.2018.09.071","article-title":"Vaccination and immunization strategies to design Aedes aegypti salivary protein based subunit vaccine tackling flavivirus infection","volume":"122","author":"Pandey","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1038\/s41467-018-05276-4","article-title":"A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein","volume":"9","author":"Li","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1080\/21645515.2019.1658503","article-title":"A review of Dengvaxia\u00ae: Development to deployment","volume":"15","author":"Thomas","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12250-018-0030-5","article-title":"Zika virus baculovirus-expressed virus-like particles induce neutralizing antibodies in mice","volume":"33","author":"Dai","year":"2018","journal-title":"Virol. Sin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1086\/590915","article-title":"Safety concerns with regard to live attenuated flavivirus vaccines","volume":"198","author":"Seligman","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_42","unstructured":"Tebas, P., Roberts, C.C., Muthumani, K., Reuschel, E.L., Kudchodkar, S.B., Zaidi, F.I., White, S., Khan, A.S., Racine, T., and Choi, H. (2017). Safety and immunogenicity of an anti-Zika virus DNA vaccine-Preliminary report. N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1099\/jgv.0.001351","article-title":"Use of Adeno-associated viral vectors to improve delivery of a DNA vaccine against dengue virus","volume":"101","author":"Poggianella","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s12275-017-7058-3","article-title":"Exploiting virus-like particles as innovative vaccines against emerging viral infections","volume":"55","author":"Jeong","year":"2017","journal-title":"J. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ymeth.2006.07.018","article-title":"Virus-like particles: Passport to immune recognition","volume":"40","author":"Grgacic","year":"2006","journal-title":"Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1128\/JVI.75.5.2204-2212.2001","article-title":"Generation and characterization of a mammalian cell line continuously expressing Japanese encephalitis virus subviral particles","volume":"75","author":"Konishi","year":"2001","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S0966-842X(03)00208-7","article-title":"Virus-like particles as immunogens","volume":"11","author":"Noad","year":"2003","journal-title":"Trends Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12985-018-0970-2","article-title":"Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope","volume":"15","author":"Metz","year":"2018","journal-title":"Virol. J."},{"key":"ref_49","first-page":"335","article-title":"Expression of tick-borne encephalitis virus prM-E protein in insect cells and studies on its antigenicity","volume":"19","author":"Liu","year":"2005","journal-title":"Chin. J. Exp. Clin. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e01181-17","DOI":"10.1128\/JVI.01181-17","article-title":"An envelope-modified tetravalent dengue virus-like-particle vaccine has implications for flavivirus vaccine design","volume":"91","author":"Urakami","year":"2017","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S1097-2765(01)00206-4","article-title":"Molecular organization of a recombinant subviral particle from tick-borne encephalitis virus","volume":"7","author":"Ferlenghi","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhou, J., Yu, Z., Fang, D., Fu, C., Zhu, X., He, Z., Yan, H., and Jiang, L. (2014). Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: Immunological properties. BMC Microbiol., 14.","DOI":"10.1186\/s12866-014-0233-3"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Boigard, H., Alimova, A., Martin, G.R., Katz, A., Gottlieb, P., and Galarza, J.M. (2017). Zika virus-like particle (VLP) based vaccine. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005608"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/978-1-4939-3389-1_25","article-title":"Production of Japanese encephalitis virus-like particles using insect cell expression systems","volume":"1404","author":"Yamaji","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.virol.2016.06.006","article-title":"Production of immunogenic West Nile virus-like particles using a herpes simplex virus 1 recombinant vector","volume":"496","author":"Taylor","year":"2016","journal-title":"Virology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.tibtech.2019.03.013","article-title":"Production and biomedical application of flavivirus-like particles","volume":"37","author":"Krol","year":"2019","journal-title":"Trends Biotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dai, S., Zhang, Y., Zhang, T., Zhang, B., Wang, H., and Deng, F. (2018). Establishment of baculovirus-expressed VLPs induced syncytial formation assay for flavivirus antiviral screening. Viruses, 10.","DOI":"10.3390\/v10070365"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.tibs.2017.02.009","article-title":"Structural biology of the Zika virus","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"ref_59","first-page":"61","article-title":"Passive transfer of immune sera induced by a Zika virus-like particle vaccine protects AG129 mice against lethal Zika virus challenge","volume":"27","author":"Espinosa","year":"2018","journal-title":"EBio Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Salvo, M.A., Kingstad-Bakke, B., Salas-Quinchucua, C., Camacho, E., and Osorio, J.E. (2018). Zika virus like particles elicit protective antibodies in mice. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006210"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.bbrc.2020.05.161","article-title":"Zika Virus-Like Particle (VLP) vaccine displaying Envelope (E) protein CD loop antigen elicits protective and specific immune response in a murine model","volume":"529","author":"Cimica","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.virusres.2016.10.005","article-title":"The flavivirus capsid protein: Structure, function and perspectives towards drug design","volume":"227","author":"Oliveira","year":"2017","journal-title":"Virus Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e00834-17","DOI":"10.1128\/JVI.00834-17","article-title":"Development of virus-like-particle vaccine and reporter assay for Zika virus","volume":"91","author":"Garg","year":"2017","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"ftz026","DOI":"10.1093\/femspd\/ftz026","article-title":"Pichia pastoris-expressed Zika virus envelope domain III on a virus-like particle platform: Design, production and immunological evaluation","volume":"77","author":"Shanmugam","year":"2019","journal-title":"Pathog. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7679","DOI":"10.1038\/s41598-017-08247-9","article-title":"Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.vaccine.2018.01.056","article-title":"Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells","volume":"36","author":"Basu","year":"2018","journal-title":"Vaccine"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1099\/0022-1317-78-8-1861","article-title":"Expression of the dengue virus structural proteins in Pichia pastoris leads to the generation of virus-like particles","volume":"78","author":"Sugrue","year":"1997","journal-title":"J. Gen. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7728","DOI":"10.1016\/j.vaccine.2018.10.072","article-title":"Dengue-2 virus-like particle (VLP) based vaccine elicits the highest titers of neutralizing antibodies when produced at reduced temperature","volume":"36","author":"Boigard","year":"2018","journal-title":"Vaccine"},{"key":"ref_69","first-page":"1986","article-title":"Induction of virus-neutralizing antibodies and T cell responses by dengue virus type 1 virus-like particles prepared from Pichia pastoris","volume":"125","author":"Tang","year":"2012","journal-title":"Chin. Med. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"126","DOI":"10.4269\/ajtmh.16-0503","article-title":"Recombinant dengue virus 4 envelope glycoprotein virus-like particles derived from Pichia pastoris are capable of eliciting homotypic domain III-directed neutralizing antibodies","volume":"96","author":"Khetarpal","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/1743-422X-8-333","article-title":"Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice","volume":"8","author":"Zhang","year":"2011","journal-title":"Virol. J."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Mani, S., Tripathi, L., Raut, R., Tyagi, P., Arora, U., Barman, T., Sood, R., Galav, A., Wahala, W., and de Silva, A. (2013). Pichia pastoris-expressed dengue 2 envelope forms virus-like particles without pre-membrane protein and induces high titer neutralizing antibodies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064595"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.1016\/j.vaccine.2015.08.090","article-title":"Generation and preclinical immunogenicity study of dengue type 2 virus-like particles derived from stably transfected mosquito cells","volume":"33","author":"Suphatrakul","year":"2015","journal-title":"Vaccine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/14760584.2019.1562909","article-title":"Next generation designer virus-like particle vaccines for dengue","volume":"18","author":"Shukla","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.vaccine.2016.02.004","article-title":"Protective and immunological behavior of chimeric yellow fever dengue vaccine","volume":"34","author":"Halstead","year":"2016","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6803098","DOI":"10.1155\/2016\/6803098","article-title":"Dengue Fever: Causes, complications, and vaccine strategies","volume":"2016","author":"Khetarpal","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Crill, W.D., Hughes, H.R., Delorey, M.J., and Chang, G.J. (2009). Humoral immune responses of dengue fever patients using epitope-specific serotype-2 virus-like particle antigens. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004991"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Poddar, A., Ramasamy, V., Shukla, R., Rajpoot, R.K., Arora, U., Jain, S.K., Swaminathan, S., and Khanna, N. (2016). Virus-like particles derived from Pichia pastoris-expressed dengue virus type 1 glycoprotein elicit homotypic virus-neutralizing envelope domain III-directed antibodies. BMC Biotechnol., 16.","DOI":"10.1186\/s12896-016-0280-y"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.vaccine.2012.12.016","article-title":"Virus-like particles displaying envelope domain III of dengue virus type 2 induce virus-specific antibody response in mice","volume":"31","author":"Arora","year":"2013","journal-title":"Vaccine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1477-3155-10-30","article-title":"Chimeric Hepatitis B core antigen virus-like particles displaying the envelope domain III of dengue virus type 2","volume":"10","author":"Arora","year":"2012","journal-title":"J. Nanobiotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3389\/fmicb.2015.01005","article-title":"Pichia pastoris-expressed dengue 3 envelope-based virus-like particles elicit predominantly domain III-focused high titer neutralizing antibodies","volume":"6","author":"Tripathi","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.3389\/fmicb.2017.02644","article-title":"Pichia pastoris-expressed bivalent virus-like particulate vaccine induces domain III-focused bivalent neutralizing antibodies without antibody-dependent enhancement in vivo","volume":"8","author":"Shukla","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8643","DOI":"10.1038\/s41598-018-26904-5","article-title":"Dengue envelope-based \u2018four-in-one\u2019 virus-like particles produced using Pichia pastoris induce enhancement-lacking, domain III-directed tetravalent neutralising antibodies in mice","volume":"8","author":"Rajpoot","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10813","DOI":"10.1128\/JVI.00810-14","article-title":"Virus-like particle secretion and genotype-dependent immunogenicity of dengue virus serotype 2 DNA vaccine","volume":"88","author":"Galula","year":"2014","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jviromet.2014.04.019","article-title":"An optimized expression vector for improving the yield of dengue virus-like particles from transfected insect cells","volume":"205","author":"Charoensri","year":"2014","journal-title":"J. Virol. Methods"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ramasamy, V., Arora, U., Shukla, R., Poddar, A., Shanmugam, R.K., White, L.J., Mattocks, M.M., Raut, R., Perween, A., and Tyagi, P. (2018). A tetravalent virus-like particle vaccine designed to display domain III of dengue envelope proteins induces multi-serotype neutralizing antibodies in mice and macaques which confer protection against antibody dependent enhancement in AG129 mice. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006191"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00253-015-6973-7","article-title":"Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences","volume":"100","author":"Mareze","year":"2016","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3390\/vaccines3030503","article-title":"Immunogenic Subviral Particles Displaying Domain III of Dengue 2 Envelope Protein Vectored by Measles Virus","volume":"3","author":"Valle","year":"2015","journal-title":"Vaccines"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/1743-422X-10-129","article-title":"A novel platform for virus-like particle-display of flaviviral envelope domain III: Induction of dengue and West Nile virus neutralizing antibodies","volume":"10","author":"Chua","year":"2013","journal-title":"Virol. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7072","DOI":"10.1128\/JVI.00224-12","article-title":"Mutagenesis of the DI\/DIII linker in dengue virus envelope protein impairs viral particle assembly","volume":"86","author":"Yang","year":"2012","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.virol.2007.12.041","article-title":"A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles","volume":"374","author":"Hsieh","year":"2008","journal-title":"Virology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1086\/425933","article-title":"Induction of sterilizing immunity against West Nile Virus (WNV), by immunization with WNV-like particles produced in insect cells","volume":"190","author":"Qiao","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6588","DOI":"10.1016\/j.vaccine.2010.07.055","article-title":"Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate","volume":"28","author":"Ohtaki","year":"2010","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/1743-422X-7-146","article-title":"A VLP-based vaccine targeting domain III of the West Nile virus E protein protects from lethal infection in mice","volume":"7","author":"Spohn","year":"2010","journal-title":"Virol. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s12033-014-9743-3","article-title":"Mosaic RNA phage VLPs carrying domain III of the West Nile virus E protein","volume":"56","author":"Cielens","year":"2014","journal-title":"Mol. Biotechnol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.diagmicrobio.2018.02.003","article-title":"Diagnostic aptitude of West Nile virus-like particles expressed in insect cells","volume":"91","author":"Rebollo","year":"2018","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.virol.2012.07.011","article-title":"Mutations in the West Nile prM protein affect VLP and virion secretion in vitro","volume":"433","author":"Calvert","year":"2012","journal-title":"Virology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1099\/vir.0.82640-0","article-title":"A detailed mutagenesis study of flavivirus cross-reactive epitopes using West Nile virus-like particles","volume":"88","author":"Crill","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.micinf.2009.07.009","article-title":"Effects of the number of amino acid residues in the signal segment upstream or downstream of the NS2B-3 cleavage site on production and secretion of prM\/M-E virus-like particles of West Nile virus","volume":"11","author":"Takahashi","year":"2009","journal-title":"Microbes Infect"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3201\/eid1501.080311","article-title":"Past, present, and future of Japanese encephalitis","volume":"15","author":"Erlanger","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2471\/BLT.10.085233","article-title":"Estimated global incidence of Japanese encephalitis: A systematic review","volume":"89","author":"Campbell","year":"2011","journal-title":"Bull. World Health Organ."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Hua, R.H., Li, Y.N., Chen, Z.S., Liu, L.K., Huo, H., Wang, X.L., Guo, L.P., Shen, N., Wang, J.F., and Bu, Z.G. (2014). Generation and characterization of a new mammalian cell line continuously expressing virus-like particles of Japanese encephalitis virus for a subunit vaccine candidate. BMC Biotechnol., 14.","DOI":"10.1186\/1472-6750-14-62"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1016\/j.vaccine.2003.12.008","article-title":"Japanese encephalitis subunit vaccine composed of virus-like envelope antigen particles purified from serum-free medium of a high-producer J12#26 cell clone","volume":"22","author":"Mutoh","year":"2004","journal-title":"Vaccine"},{"key":"ref_104","first-page":"863","article-title":"Secreted expression of Japanese encephalitis virus prME in Pichia pastoris and immunogenicity evaluation of the virus-like particles in mice","volume":"33","author":"Zhao","year":"2017","journal-title":"Chin. J. Biotechnol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"438","DOI":"10.4161\/bioe.24514","article-title":"Production of Japanese encephalitis virus-like particles in insect cells","volume":"4","author":"Yamaji","year":"2013","journal-title":"Bioengineered"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.jbiosc.2012.06.012","article-title":"Production of Japanese encephalitis virus-like particles using the baculovirus-insect cell system","volume":"114","author":"Yamaji","year":"2012","journal-title":"J. Biosci. Bioeng."},{"key":"ref_107","first-page":"150","article-title":"Generation of Japanese Encephalitis Virus-like Particle Vaccine and Preliminary Evaluation of Its Protective Efficiency","volume":"32","author":"Zhang","year":"2016","journal-title":"Bing Du Xue Bao"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"8745","DOI":"10.1128\/JVI.77.16.8745-8755.2003","article-title":"Stable high-producer cell clone expressing virus-like particles of the Japanese encephalitis virus e protein for a second-generation subunit vaccine","volume":"77","author":"Kojima","year":"2003","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1128\/CVI.05412-11","article-title":"Poly-gamma-glutamic acid nanoparticles and aluminum adjuvant used as an adjuvant with a single dose of Japanese encephalitis virus-like particles provide effective protection from Japanese encephalitis virus","volume":"19","author":"Okamoto","year":"2012","journal-title":"Clin. Vacc. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e00286","DOI":"10.1016\/j.heliyon.2017.e00286","article-title":"Development of a Japanese encephalitis virus-like particle vaccine in silkworms using codon-optimised prM and envelope genes","volume":"3","author":"Matsuda","year":"2017","journal-title":"Heliyon"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1099\/jgv.0.001081","article-title":"Development of a Japanese encephalitis virus genotype V virus-like particle vaccine in silkworms","volume":"99","author":"Nerome","year":"2018","journal-title":"J. Gen. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1038\/s41598-018-25596-1","article-title":"Genotype I of Japanese encephalitis virus virus-like particles elicit sterilizing immunity against genotype I and III viral challenge in swine","volume":"8","author":"Fan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1128\/JVI.77.6.3487-3494.2003","article-title":"A Japanese encephalitis virus peptide present on Johnson grass mosaic virus-like particles induces virus-neutralizing antibodies and protects mice against lethal challenge","volume":"77","author":"Saini","year":"2003","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"De Wispelaere, M., Ricklin, M., Souque, P., Frenkiel, M.P., Paulous, S., Garcia-Nicolas, O., Summerfield, A., Charneau, P., and Despres, P. (2015). A lentiviral vector expressing Japanese encephalitis virus-like particles elicits broad neutralizing antibody response in pigs. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004081"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1099\/vir.0.82824-0","article-title":"Construction and application of chimeric virus-like particles of tick-borne encephalitis virus and mosquito-borne Japanese encephalitis virus","volume":"89","author":"Yoshii","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4149\/av_2013_01_27","article-title":"N-glycosylation of the premembrane protein of Japanese encephalitis virus is critical for folding of the envelope protein and assembly of virus-like particles","volume":"57","author":"Zai","year":"2013","journal-title":"Acta Virol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"7846","DOI":"10.1128\/JVI.00789-08","article-title":"A single N-linked glycosylation site in the Japanese encephalitis virus prM protein is critical for cell type-specific prM protein biogenesis, virus particle release, and pathogenicity in mice","volume":"82","author":"Kim","year":"2008","journal-title":"J. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1099\/jgv.0.000833","article-title":"A relevant in vitro human model for the study of Zika virus antibody-dependent enhancement","volume":"98","author":"Troupin","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1128\/JCM.43.7.3227-3236.2005","article-title":"Comparative analysis of immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay using virus-like particles or virus-infected mouse brain antigens to detect IgM antibody in sera from patients with evident flaviviral infections","volume":"43","author":"Holmes","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.antiviral.2010.02.313","article-title":"A high-throughput assay using dengue-1 virus-like particles for drug discovery","volume":"86","author":"Qing","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1128\/AAC.49.12.4980-4988.2005","article-title":"High-throughput assays using a luciferase-expressing replicon, virus-like particles, and full-length virus for West Nile virus drug discovery","volume":"49","author":"Deas","year":"2005","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/3\/481\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:07:37Z","timestamp":1760177257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/3\/481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,27]]},"references-count":121,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["vaccines8030481"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8030481","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,27]]}}}