title: Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes.
abstract: The WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine (IPV). However, high-cost, limited supply of IPV, persistent circulating vaccine-derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low-cost cold chain-free plant-made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50-fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant-derived adjuvants after single priming with IPV significantly increased VP1-IgG1 and VP1-IgA titres when compared to lower IgG1 or negligible IgA titres with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titres (~3.17-10.17 log2titre) and seropositivity (70-90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant-cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA-approved antigens and adjuvants are discussed.
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Chan
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Weldon
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Oberste
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chumakov
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA. hdaniell@upenn.edu.
authors.forename: Henry
authors.initials: H
authors.lastname: Daniell
mesh_terms: D002736:Chloroplasts / Q000276:immunology*; D003141:Communicable Diseases; D006801:Humans; D058634:Molecular Farming; D011055:Poliovirus Vaccine, Oral / Q000276:immunology*; D014611:Vaccination
chemical_list: D011055:Poliovirus Vaccine, Oral
keywords: bioencapsulation; chloroplast transformation; human infectious diseases; molecular farming; mucosal immunity; oral delivery