Abstract
Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.
Keywords: emerging infectious disease, self-assembly, vaccine, virus, virus-like particle (VLP)
Footnotes
ORCID: 0000-0002-5385-083X
References
- Acuna R, Cifuentes-Munoz N, Marquez CL, Bulling M, Klingstrom J, Mancini R, Lozach PY, Tischler ND. Hantavirus Gn and Gc glycoproteins self-assemble into virus-like particles. J Virol. 2014;88:2344–2348. doi: 10.1128/JVI.03118-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Akahata W, Yang ZY, Andersen H, Sun S, Holdaway HA, Kong WP, Lewis MG, Higgs S, Rossmann MG, Rao S, Nabel GJ. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat Med. 2010;16:334–338. doi: 10.1038/nm.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen WH, Ferreira J, Estes MK, Graham DY, Opekun AR, Richardson C, Mendelman PM. Norovirus Vaccine against Experimental Human Norwalk Virus Illness. New Engl J Med. 2011;365:2178–2187. doi: 10.1056/NEJMoa1101245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bai B, Hu Q, Hu H, Zhou P, Shi Z, Meng J, Lu B, Huang Y, Mao P, Wang H. Virus-like particles of SARS-like coronavir-us formed by membrane proteins from different origins demon-strate stimulating activity in human dendritic cells. PLoS One. 2008;3:2685. doi: 10.1371/journal.pone.0002685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keita S, de Clerck H, Tiffany A, Dominguez G, Loua M, Traore A, Kolie M, Malano ER, Heleze E, Bocquin A, Mely S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, van Herp M, Gunther S. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014;371:1418–1425. doi: 10.1056/NEJMoa1404505. [DOI] [PubMed] [Google Scholar]
- Ball JM, Estes MK, Hardy ME, Conner ME, Opekun AR, Graham DY. Recombinant Norwalk virus-like particles as an oral vaccine. Arch Virol, Suppl. 1996;12:243–249. doi: 10.1007/978-3-7091-6553-9_26. [DOI] [PubMed] [Google Scholar]
- Ball JM, Hardy ME, Atmar RL, Conner ME, Estes MK. Oral immunization with recombinant Norwalk virus-like particles induces a systemic and mucosal immune response in mice. J Virol. 1998;72:1345–1353. doi: 10.1128/jvi.72.2.1345-1353.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Branco LM, Grove JN, Geske FJ, Boisen ML, Muncy IJ, Magliato SA, Henderson LA, Schoepp RJ, Cashman KA, Hensley LE, Garry RF. Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever. Virol J. 2010;7:279. doi: 10.1186/1743-422X-7-279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bright RA, Carter DM, Crevar CJ, Toapanta FR, Steckbeck JD, Cole KS, Kumar NM, Pushko P, Smith G, Tumpey TM, Ross TM. Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle. PLoS One. 2008;3:1501. doi: 10.1371/journal.pone.0001501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buonaguro L, Tagliamonte M, Tornesello ML, Buonaguro FM. Developments in virus-like particle-based vaccines for infectious diseases and cancer. Expert Rev Vaccines. 2011;10:1569–1583. doi: 10.1586/erv.11.135. [DOI] [PubMed] [Google Scholar]
- Buonaguro L, Visciano ML, Tornesello ML, Tagliamonte M, Biryahwaho B, Buonaguro FM. Induction of systemic and mucosal cross-clade neutralizing antibodies in BALB/c mice immunized with human immunodeficiency virus type 1 clade A virus -like particles administered by different routes of inoculation. J Virol. 2005;79:7059–7067. doi: 10.1128/JVI.79.11.7059-7067.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chackerian B, Lenz P, Lowy DR, Schiller JT. Determinants of autoantibody induction by conjugated papillomavirus virus-like particles. J Immunol. 2002;169:6120–6126. doi: 10.4049/jimmunol.169.11.6120. [DOI] [PubMed] [Google Scholar]
- Cox RG, Erickson JJ, Hastings AK, Becker JC, Johnson M, Craven RE, Tollefson SJ, Boyd KL, Williams JV. Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model. J Virol. 2014;88:6368–6379. doi: 10.1128/JVI.00332-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- D’Aoust MA, Couture MM, Charland N, Trepanier S, Landry N, Ors F, Vezina LP. The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza. Plant Biotechnol J. 2010;8:607–619. doi: 10.1111/j.1467-7652.2009.00496.x. [DOI] [PubMed] [Google Scholar]
- de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, Enjuanes L, Fouchier RAM, Galiano M, Gorbalenya AE, Memish ZA, Perlman S, Poon LLM, Snijder EJ, Stephens GM, Woo PCY, Zaki AM, Zambon M, Ziebuhr J. Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group. J Virol. 2013;87:7790–7792. doi: 10.1128/JVI.01244-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Du R, Yin F, Wang M, Hu Z, Wang H, Deng F. Glycoprotein E of the Japanese encephalitis virus forms virus-like particles and induces syncytia when expressed by a baculovirus. J Gen Virol. 2015;96:1006–1014. doi: 10.1099/vir.0.000052. [DOI] [PubMed] [Google Scholar]
- El-Kamary SS, Pasetti MF, Mendelman PM, Frey SE, Bernstein DI, Treanor JJ, Ferreira J, Chen WH, Sublett R, Richardson C, Bargatze RF, Sztein MB, Tacket CO. Adjuvanted Intranasal Norwalk Virus-Like Particle Vaccine Elicits Antibodies and Antibody- Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues. J Infect Dis. 2010;202:1649–1658. doi: 10.1086/657087. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garcia-Sastre A, Mena I. Novel vaccine strategies against emerging viruses. Curr Opin Virol. 2013;3:210–216. doi: 10.1016/j.coviro.2013.02.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrington PR, Yount B, Johnston RE, Davis N, Moe C, Baric RS. Systemic, mucosal, and heterotypic immune induction in mice inoculated with Venezuelan equine encephalitis replicons expressing Norwalk virus-like particles. J Virol. 2002;76:730–742. doi: 10.1128/JVI.76.2.730-742.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrison MS, Sakaguchi T, Schmitt AP. Paramyxovirus assembly and budding: building particles that transmit infections. Int J Biochem Cell Biol. 2010;42:1416–1429. doi: 10.1016/j.biocel.2010.04.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herbst-Kralovetz M, Mason HS, Chen Q. Norwalk virus-like particles as vaccines. Expert Rev Vaccines. 2010;9:299–307. doi: 10.1586/erv.09.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes DA, Purdy DE, Chao DY, Noga AJ, Chang GJ. Comparative analysis of immunoglobulin M (IgM) capture enzymelinked immunosorbent assay using virus-like particles or virusinfected mouse brain antigens to detect IgM antibody in sera from patients with evident flaviviral infections. J Clin Microbiol. 2005;43:3227–3236. doi: 10.1128/JCM.43.7.3227-3236.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kang SM, Song JM, Quan FS, Compans RW. Influenza vaccines based on virus-like particles. Virus Res. 2009;143:140–146. doi: 10.1016/j.virusres.2009.04.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Khurana S, Wu J, Verma N, Verma S, Raghunandan R, Manischewitz J, King LR, Kpamegan E, Pincus S, Smith G, Glenn G, Golding H. H5N1 virus-like particle vaccine elicits crossreactive neutralizing antibodies that preferentially bind to the oligomeric form of influenza virus hemagglutinin in humans. J Virol. 2011;85:10945–10954. doi: 10.1128/JVI.05406-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kong D, Wen Z, Su H, Ge J, Chen W, Wang X, Wu C, Yang C, Chen H, Bu Z. Newcastle disease virus-vectored Nipah encephalitis vaccines induce B and T cell responses in mice and long-lasting neutralizing antibodies in pigs. Virology. 2012;432:327–335. doi: 10.1016/j.virol.2012.06.001. [DOI] [PubMed] [Google Scholar]
- L’Vov D K, Al’khovskii SV, Shchelkanov M, Shchetinin AM, Deriabin PG, Aristova VA, Gitel’man AK, Samokhvalov EI, Botikov AG. Taxonomic status of the Tyulek virus (TLKV) (Orthomyxoviridae, Quaranjavirus, Quaranfil group) isolated from the ticks Argas vulgaris Filippova, 1961 (Argasidae) from the birds burrow nest biotopes in the Kyrgyzstan. Vopr Virusol. 2014;59:28–32. [PubMed] [Google Scholar]
- López-Macías C, Ferat-Osorio E, Tenorio-Calvo A, Isibasi A, Talavera J, Arteaga-Ruiz O, Arriaga-Pizano L, Hickman SP, Allende M, Lenhard K, Pincus S, Connolly K, Raghunandan R, Smith G, Glenn G. Safety and immunogenicity of a viruslike particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico. Vaccine. 2011;29:7826–7834. doi: 10.1016/j.vaccine.2011.07.099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Landry N, Ward BJ, Trépanier S, Montomoli E, Dargis M, Lapini G, Vézina L-P. Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza. PLoS One. 2010;5:15559. doi: 10.1371/journal.pone.0015559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li C, Liu F, Liang M, Zhang Q, Wang X, Wang T, Li J, Li D. Hantavirus-like particles generated in CHO cells induce specific immune responses in C57BL/6 mice. Vaccine. 2010;28:4294–4300. doi: 10.1016/j.vaccine.2010.04.025. [DOI] [PubMed] [Google Scholar]
- Lindesmith LC, Ferris MT, Mullan CW, Ferreira J, Debbink K, Swanstrom J, Richardson C, Goodwin RR, Baehner F, Mendelman PM, Bargatze RF, Baric RS. Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial. PLoS Med. 2015;12:32. doi: 10.1371/journal.pmed.1001807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu Y, Zhou J, Yu Z, Fang D, Fu C, Zhu X, He Z, Yan H, Jiang L. Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties. BMC Microbiol. 2014;14:233. doi: 10.1186/s12866-014-0233-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lu B, Huang Y, Huang L, Li B, Zheng Z, Chen Z, Chen J, Hu Q, Wang H. Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice. Immunology. 2010;130:254–261. doi: 10.1111/j.1365-2567.2010.03231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandell RB, Koukuntla R, Mogler LJ, Carzoli AK, Freiberg AN, Holbrook MR, Martin BK, Staplin WR, Vahanian NN, Link CJ, Flick R. A replication-incompetent Rift Valley fever vaccine: chimeric virus-like particles protect mice and rats against lethal challenge. Virology. 2010;397:187–198. doi: 10.1016/j.virol.2009.11.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mani S, Tripathi L, Raut R, Tyagi P, Arora U, Barman T, Sood R, Galav A, Wahala W, de Silva A, Swaminathan S, Khanna N. Pichia pastoris-expressed dengue 2 envelope forms viruslike particles without pre-membrane protein and induces high titer neutralizing antibodies. PLoS One. 2013;8:64595. doi: 10.1371/journal.pone.0064595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGinnes LW, Gravel KA, Finberg RW, Kurt-Jones EA, Massare MJ, Smith G, Schmidt MR, Morrison TG. Assembly and immunological properties of Newcastle disease virus-like particles containing the respiratory syncytial virus F and G proteins. J Virol. 2011;85:366–377. doi: 10.1128/JVI.01861-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metz SW, Gardner J, Geertsema C, Le TT, Goh L, Vlak JM, Suhrbier A, Pijlman GP. Effective chikungunya virus-like particle vaccine produced in insect cells. PLoS Negl Trop Dis. 2013;7:2124. doi: 10.1371/journal.pntd.0002124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore MD, Goulter RM, Jaykus LA. Human norovirus as a foodborne pathogen: challenges and developments. Annu Rev Food Sci Technol. 2015;6:411–433. doi: 10.1146/annurev-food-022814-015643. [DOI] [PubMed] [Google Scholar]
- Mortola E, Roy P. Efficient assembly and release of SARS coronavirus-like particles by a heterologous expression system. FEBS Lett. 2004;576:174–178. doi: 10.1016/j.febslet.2004.09.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Noranate N, Takeda N, Chetanachan P, Sittisaman P A A, Anantapreecha S. Characterization of chikungunya viruslike particles. PLoS One. 2014;9:108169. doi: 10.1371/journal.pone.0108169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oldstone MBA. Arenaviruses I -The epidemiology, molecular and cell biology of arenaviruses -Preface. Arenaviruses I. 2002;262:V–Xii. [PubMed] [Google Scholar]
- Overby AK, Popov V, Neve EP, Pettersson RF. Generation and analysis of infectious virus-like particles of uukuniemi virus (bunyaviridae): a useful system for studying bunyaviral packaging and budding. J Virol. 2006;80:10428–10435. doi: 10.1128/JVI.01362-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel MM, Hall AJ, Vinje J, Parashara UD. Noroviruses: A comprehensive review. J Clin Virol. 2009;44:1–8. doi: 10.1016/j.jcv.2008.10.009. [DOI] [PubMed] [Google Scholar]
- Purdy DE, Chang GJ. Secretion of noninfectious dengue viruslike particles and identification of amino acids in the stem region involved in intracellular retention of envelope protein. Virology. 2005;333:239–250. doi: 10.1016/j.virol.2004.12.036. [DOI] [PubMed] [Google Scholar]
- Quan FS, Huang C, Compans RW, Kang SM. Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus. J Virol. 2007;81:3514–3524. doi: 10.1128/JVI.02052-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quan FS, Kim Y, Lee S, Yi H, Kang SM, Bozja J, Moore ML, Compans RW. Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice. J Infect Dis. 2011;204:987–995. doi: 10.1093/infdis/jir474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ramani S, Atmar RL, Estes MK. Epidemiology of human noroviruses and updates on vaccine development. Curr Opin Gastroenterol. 2014;30:25–33. doi: 10.1097/MOG.0000000000000022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rodriguez-Limas WA, Sekar K, Tyo KE. Virus-like particles: the future of microbial factories and cell-free systems as platforms for vaccine development. Curr Opin Biotechnol. 2013;24:1089–1093. doi: 10.1016/j.copbio.2013.02.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roldão A, Mellado MCM, Castilho LR, Carrondo MJT, Alves PM. Virus-like particles in vaccine development. Expert Rev Vaccines. 2010;9:1149–1176. doi: 10.1586/erv.10.115. [DOI] [PubMed] [Google Scholar]
- Schmeisser F, Adamo JE, Blumberg B, Friedman R, Muller J, Soto J, Weir JP. Production and characterization of mammalian virus-like particles from modified vaccinia virus Ankara vectors expressing influenza H5N1 hemagglutinin and neuraminidase. Vaccine. 2012;30:3413–3422. doi: 10.1016/j.vaccine.2012.03.033. [DOI] [PubMed] [Google Scholar]
- Schweitzer BK, Chapman NM, Iwen PC. Overview of the Flaviviridae With an Emphasis on the Japanese Encephalitis Group Viruses. Lab Medicine. 2009;40:493–499. doi: 10.1309/LM5YWS85NJPCWESW. [DOI] [Google Scholar]
- Scotti N, Rybicki EP. Virus-like particles produced in plants as potential vaccines. Expert Rev Vaccines. 2013;12:211–224. doi: 10.1586/erv.12.147. [DOI] [PubMed] [Google Scholar]
- Singh G, Kumar A, Singh K, Kaur J. Rev Med Virol. 2015. Ebola virus: an introduction and its pathology. [DOI] [PubMed] [Google Scholar]
- Staples JE, Breiman RF, Powers AM. Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis. 2009;49:942–948. doi: 10.1086/605496. [DOI] [PubMed] [Google Scholar]
- Strecker T, Eichler R, Meulen J, Weissenhorn W D, Klenk H, Garten W, Lenz O. Lassa virus Z protein is a matrix protein sufficient for the release of virus-like particles. J Virol. 2003;77:10700–10705. doi: 10.1128/JVI.77.19.10700-10705.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swayne DE, Suarez DL. Highly pathogenic avian influenza. Rev Sci Tech. 2000;19:463–482. doi: 10.20506/rst.19.2.1230. [DOI] [PubMed] [Google Scholar]
- Swenson DL, Warfield KL, Kuehl K, Larsen T, Hevey MC, Schmaljohn A, Bavari S, Aman MJ. Generation of Marburg virus-like particles by co-expression of glycoprotein and matrix protein. FEMS Immunol Med Microbiol. 2004;40:27–31. doi: 10.1016/S0928-8244(03)00273-6. [DOI] [PubMed] [Google Scholar]
- Wagner R, Deml L, Schirmbeck R, Reimann J, Wolf H. Induction of a MHC class I-restricted, CD8 positive cytolytic T-cell response by chimeric HIV-1 virus-like particles in vivo: implications on HIV vaccine development. Behring Inst Mitt. 1994;95:23–34. [PubMed] [Google Scholar]
- Walpita P, Barr J, Sherman M, Basler CF, Wang L. Vaccine Potential of Nipah Virus-Like Particles. PLoS One. 2011;6:18437. doi: 10.1371/journal.pone.0018437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warfield KL, Aman MJ. Advances in virus-like particle vaccines for filoviruses. J Infect Dis. 2011;204:S1053–S1059. doi: 10.1093/infdis/jir346. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warfield KL, Bosio CM, Welcher BC, Deal EM, Mohamadzadeh M, Schmaljohn A, Aman MJ, Bavari S. Ebola virus-like particles protect from lethal Ebola virus infection. Proc Natl Acad Sci U S A. 2003;100:15889–15894. doi: 10.1073/pnas.2237038100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warfield KL, Posten NA, Swenson DL, Olinger GG, Esposito D, Gillette WK, Hopkins RF, Costantino J, Panchal RG, Hartley JL, Aman MJ, Bavari S. Filovirus-like particles produced in insect cells: immunogenicity and protection in rodents. J Infect Dis. 2007;196:S421–S429. doi: 10.1086/520612. [DOI] [PubMed] [Google Scholar]
- WHO 2015. Ebola Situation Report 21 Oct 2015. http://apps.who. int/iris/bitstream/10665/190067/1/ebolasitrep21Oct2015_eng.pdf
- WHO 2016. Middle East respiratory syndrome coronavirus (MERSCoV)–Saudi Arabia. 22 June 2016. http://www.who.int/csr/don/22-june-2016-mers-saudi-arabia/en/
- Yamaji H, Nakamura M, Kuwahara M, Takahashi Y, Katsuda T, Konishi E. Efficient production of Japanese encephalitis virus-like particles by recombinant lepidopteran insect cells. Appl Microbiol Biotechnol. 2013;97:1071–1079. doi: 10.1007/s00253-012-4371-y. [DOI] [PubMed] [Google Scholar]
- Yang L, Song Y, Li X, Huang X, Liu J, Ding H, Zhu P, Zhou P. HIV-1 virus-like particles produced by stably transfected Drosophila S2 cells: a desirable vaccine component. J Virol. 2012;86:7662–7676. doi: 10.1128/JVI.07164-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeltins A. Construction and characterization of virus-like particles: a review. Mol Biotechnol. 2013;53:92–107. doi: 10.1007/s12033-012-9598-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhang S, Liang M, Gu W, Li C, Miao F, Wang X, Jin C, Zhang L, Zhang F, Zhang Q, Jiang L, Li M, Li D. Vaccination with dengue virus-like particles induces humoral and cellular immune responses in mice. Virol J. 2011;8:333. doi: 10.1186/1743-422X-8-333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhao Q, Li S, Yu H, Xia N, Modis Y. Virus-like particlebased human vaccines: quality assessment based on structural and functional properties. Trends Biotechnol. 2013;31:654–663. doi: 10.1016/j.tibtech.2013.09.002. [DOI] [PubMed] [Google Scholar]
- Zhou ZR, Wang ML, Deng F, Li TX, Hu ZH, Wang HL. Production of CCHF virus-like particle by a baculovirus-insect cell expression system. Virol Sin. 2011;26:338–346. doi: 10.1007/s12250-011-3209-6. [DOI] [PMC free article] [PubMed] [Google Scholar]