{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:27:32Z","timestamp":1785220052356,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T00:00:00Z","timestamp":1503446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["# R33AI101329"],"award-info":[{"award-number":["# R33AI101329"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Plant Biotechnology Journal"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The global Zika virus (<jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content>) outbreak and its link to foetal and newborn microcephaly and severe neurological complications in adults call for the urgent development of <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> vaccines. In response, we developed a subunit vaccine based on the <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> envelope (E) protein and investigated its immunogenicity in mice. Transient expression of <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> E (<jats:styled-content style=\"fixed-case\">zE<\/jats:styled-content>) resulted in its rapid accumulation in leaves of <jats:italic>Nicotiana benthamiana<\/jats:italic> plants. Biochemical analysis revealed that plant\u2010produced <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> E (PzE) exhibited specific binding to a panel of monoclonal antibodies that recognize various <jats:styled-content style=\"fixed-case\">zE<\/jats:styled-content> conformational epitopes. Furthermore, PzE can be purified to &gt;90% homogeneity with a one\u2010step Ni<jats:sup>2+<\/jats:sup> affinity chromatography process. PzE are found to be highly immunogenic, as two doses of PzE elicited both potent <jats:styled-content style=\"fixed-case\">zE<\/jats:styled-content>\u2010specific antibody and cellular immune responses in mice. The delivery of PzE with alum induced a mixed Th1\/Th2 immune response, as the antigen\u2010specific IgG isotypes were a mixture of high levels of IgG1\/IgG2c and splenocyte cultures from immunized mice secreted significant levels of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010gamma, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106. Most importantly, the titres of <jats:styled-content style=\"fixed-case\">zE<\/jats:styled-content>\u2010specific and neutralizing antibodies exceeded the threshold that correlates with protective immunity against multiple strains of <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content>. Thus, our results demonstrated the feasibility of plant\u2010produced <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> protein antigen as effective, safe and affordable vaccines against ZIKV.<\/jats:p>","DOI":"10.1111\/pbi.12796","type":"journal-article","created":{"date-parts":[[2017,7,15]],"date-time":"2017-07-15T08:42:48Z","timestamp":1500108168000},"page":"572-580","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Plant\u2010produced Zika virus envelope protein elicits neutralizing immune responses that correlate with protective immunity against Zika virus in mice"],"prefix":"10.1111","volume":"16","author":[{"given":"Ming","family":"Yang","sequence":"first","affiliation":[{"name":"The Biodesign Institute Arizona State University Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Sun","sequence":"additional","affiliation":[{"name":"The Biodesign Institute Arizona State University Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafang","family":"Lai","sequence":"additional","affiliation":[{"name":"The Biodesign Institute Arizona State University Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Hurtado","sequence":"additional","affiliation":[{"name":"School of Life Sciences Arizona State University Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-7013","authenticated-orcid":false,"given":"Qiang","family":"Chen","sequence":"additional","affiliation":[{"name":"The Biodesign Institute Arizona State University Tempe AZ USA"},{"name":"School of Life Sciences Arizona State University Tempe AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah6157"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2015.28"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2005.72.189"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00562-6"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.12575"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.13031\/2013.26854"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1201\/b10952-5"},{"key":"e_1_2_6_9_1","first-page":"64","article-title":"Turning a new leaf","volume":"2","author":"Chen Q.","year":"2011","journal-title":"Eur. 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