title: Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination.
abstract: Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed. An average of 30 mug of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro. Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism.
authors.affiliation: *Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takagi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.forename: Takehiro
authors.initials: T
authors.lastname: Masumura
authors.forename: Mio
authors.initials: M
authors.lastname: Mejima
authors.forename: Ushio
authors.initials: U
authors.lastname: Nakanishi
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Uozumi
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
authors.forename: Shigeto
authors.initials: S
authors.lastname: Morita
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Fumio
authors.initials: F
authors.lastname: Takaiwa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D000906:Antibodies; D000917:Antibody Formation; D002772:Cholera Toxin; D022121:Cholera Vaccines; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007074:Immunoglobulin G; D051379:Mice; D012275:Oryza / Q000235:genetics*; D010581:Peyer's Patches / Q000378:metabolism; D012639:Seeds / Q000235:genetics; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000906:Antibodies; D022121:Cholera Vaccines; D007074:Immunoglobulin G; D014612:Vaccines; D002772:Cholera Toxin