Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination.
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.
Nochi
Tomonori
T
*Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Takagi
Hidenori
H
Yuki
Yoshikazu
Y
Yang
Lijun
L
Masumura
Takehiro
T
Mejima
Mio
M
Nakanishi
Ushio
U
Matsumura
Akiko
A
Uozumi
Akihiro
A
Hiroi
Takachika
T
Morita
Shigeto
S
Tanaka
Kunisuke
K
Takaiwa
Fumio
F
Kiyono
Hiroshi
H
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*
D000906:Antibodies; D022121:Cholera Vaccines; D007074:Immunoglobulin G; D014612:Vaccines; D002772:Cholera Toxin