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Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We identified two regions within the envelope protein, a structural component of chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner and is thus capable of inducing strong immune responses against any inserted antigen. Furthermore, by mimicking the structure of the immature form of the virus, we altered our VLP's<jats:italic>in vivo<\/jats:italic>dynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of the<jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>malaria parasite as an antigen and demonstrated that our VLP-based vaccine elicits strong immune responses against CSP in animals. The sera from immunized monkeys protected mice from malaria infection. Likewise, mice vaccinated with<jats:named-content content-type=\"genus-species\">P. yoelii<\/jats:named-content>CSP-containing VLPs were protected from an infectious sporozoite challenge. Hence, our uniquely engineered VLP platform can serve as a blueprint for the development of vaccines against other pathogens and diseases.<\/jats:p>","DOI":"10.1128\/cvi.00090-17","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:40:23Z","timestamp":1495068023000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus"],"prefix":"10.1128","volume":"24","author":[{"given":"Akane","family":"Urakami","sequence":"first","affiliation":[{"name":"VLP Therapeutics, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Sakurai","sequence":"additional","affiliation":[{"name":"VLP Therapeutics, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoko","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"VLP Therapeutics, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moh Lan","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevel","family":"Flores-Garcia","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunari","family":"Haseda","sequence":"additional","affiliation":[{"name":"Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Aoshi","sequence":"additional","affiliation":[{"name":"Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fidel P.","family":"Zavala","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Rossmann","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Kuno","sequence":"additional","affiliation":[{"name":"VLP Therapeutics, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Ueno","sequence":"additional","affiliation":[{"name":"VLP Therapeutics, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Akahata","sequence":"additional","affiliation":[{"name":"VLP Therapeutics, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(03)00208-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.6.3.381"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.10.115"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.10.083"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.119"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009809"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19234"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400065"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"404","DOI":"10.4049\/jimmunol.140.2.404","article-title":"Receptor-mediated B cell antigen processing. 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