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

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

PNAS 104:10986-10991, 2007
Tomonori Nochi1,2, Hidenori Takagi3, Yoshikazu Yuki1,2, Lijun Yang3, Takehiro Masumura4, Mio Mejima1,2, Ushio Nakanishi1, Akiko Matsumura1,2, Akihiro Uozumi1, Takachika Hiroi5, Shigeto Morita4, Kunisuke Tanaka4, Fumio Takaiwa3, and Hiroshi Kiyono1,2
1: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
2: Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST)
3: Plant Biotechnology Department, National Institute of Agrobiological Sciences
4: Laboratory of Genetic Engineering, Graduate School of Agriculture, Kyoto Prefectural University
5: Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science

Mucosal vaccination is considered ideal for the global control of infectious diseases since it is capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle. We here developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) as a cholera vaccine. An average of 30 µg of CTB per seed was stored in the protein body, a storage organelle of rice seed. Orally fed rice seeds expressing CTB induced antigen-specific serum IgG and mucosal IgA responses with neutralizing activity through antigen-sampling M cells. 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 more than 1.5 years. Because they would require neither needles nor refrigeration ("cold-chain management"), these rice-based mucosal vaccines offer a highly practical as well as cost-effective strategy against infectious diseases occurred naturally or stemmed from acts of bioterrorism.