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To date, there is no virus\u2010free and cold chain\u2010free polio vaccine capable of inducing robust mucosal immunity. We report here a novel low\u2010cost, cold chain\/poliovirus\u2010free, booster vaccine using poliovirus capsid protein (<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1, conserved in all serotypes) fused with cholera non\u2010toxic B subunit (<jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>) expressed in lettuce chloroplasts. <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> using unique primer sets confirmed site\u2010specific integration of <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1 transgene cassettes. Absence of the native chloroplast genome in Southern blots confirmed homoplasmy. Codon optimization of the <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1 coding sequence enhanced its expression 9\u201315\u2010fold in chloroplasts. <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>1\u2010ganglioside receptor\u2010binding <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> confirmed pentamer assembly of <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1 fusion protein, fulfilling a key requirement for oral antigen delivery through gut epithelium. Transmission Electron Microscope images and hydrodynamic radius analysis confirmed <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1\u2010<jats:styled-content style=\"fixed-case\">VLP<\/jats:styled-content>s of 22.3\u00a0nm size. Mice primed with <jats:styled-content style=\"fixed-case\">IPV<\/jats:styled-content> and boosted three times with lyophilized plant cells expressing <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1co, formulated with plant\u2010derived oral adjuvants, enhanced <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1\u2010specific IgG1, <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1\u2010IgA titres and neutralization (80%\u2013100% seropositivity of Sabin\u20101, 2, 3). In contrast, <jats:styled-content style=\"fixed-case\">IPV<\/jats:styled-content> single dose resulted in &lt;50% <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1\u2010IgG1 and negligible <jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1\u2010IgA titres, poor neutralization and seropositivity (&lt;20%, &lt;40% Sabin 1,2). Mice orally boosted with <jats:styled-content style=\"fixed-case\">CTB<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">VP<\/jats:styled-content>1co, without <jats:styled-content style=\"fixed-case\">IPV<\/jats:styled-content> priming, failed to produce any protective neutralizing antibody. Because global population is receiving <jats:styled-content style=\"fixed-case\">IPV<\/jats:styled-content> single dose, booster vaccine free of poliovirus or cold chain offers a timely low\u2010cost solution to eradicate polio.<\/jats:p>","DOI":"10.1111\/pbi.13060","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T17:36:36Z","timestamp":1545413796000},"page":"1357-1368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Cold chain and virus\u2010free oral polio booster vaccine made in lettuce chloroplasts confers protection against all three poliovirus serotypes"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4485-1176","authenticated-orcid":false,"given":"Henry","family":"Daniell","sequence":"first","affiliation":[{"name":"Department of Biochemistry School of Dental Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineeta","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Dental Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Dental Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.384"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-7652.2007.00258.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2868"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins7030974"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-7652.2010.00582.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00147-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/pbi.12575"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.22218"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-015-0951-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120215-035349"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-7652.2009.00479.x"},{"key":"e_1_2_7_13_1","first-page":"640","article-title":"Update on vaccine\u2010derived polioviruses \u2013 Worldwide, January 2014\u2010March 2015","volume":"64","author":"Diop O.M.","year":"2015","journal-title":"MMWR Morb. 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