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Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination

Nochi, Tomonori, Takagi, Hidenori, Yuki, Yoshikazu, Yang, Lijun, Masumura, Takehiro, Mejima, Mio, Nakanishi, Ushio, Matsumura, Akiko, Uozumi, Akihiro, Hiroi, Takachika, Morita, Shigeto, Tanaka, Kunisuke, Takaiwa, Fumio, Kiyono, Hiroshi
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.26 pp. 10986-10991
Oryza sativa, rice, transgenic plants, recombinant vaccines, biopharmaceuticals, Vibrio cholerae, cholera toxin, recombinant antigens, oral administration, oral vaccination, food intake, antibody formation, mucosal immunity, immunoglobulin A, immunoglobulin G, edible vaccines
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 μg 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.