Secretory IgA-mediated protection against V. cholerae and heat-labile enterotoxin-producing enterotoxigenic Escherichia coli by rice-based vaccine.
Cholera and enterotoxigenic Escherichia coli (ETEC) are among the most common causes of acute infantile gastroenteritis globally. We previously developed a rice-based vaccine that expressed cholera toxin B subunit (MucoRice-CTB) and had the advantages of being cold chain-free and providing protection against cholera toxin (CT)-induced diarrhea. To advance the development of MucoRice-CTB for human clinical application, we investigated whether the CTB-specific secretory IgA (SIgA) induced by MucoRice-CTB gives longstanding protection against diarrhea induced by Vibrio cholerae and heat-labile enterotoxin (LT)-producing ETEC (LT-ETEC) in mice. Oral immunization with MucoRice-CTB stored at room temperature for more than 3 y provided effective SIgA-mediated protection against CT- or LT-induced diarrhea, but the protection was impaired in polymeric Ig receptor-deficient mice lacking SIgA. The vaccine gave longstanding protection against CT- or LT-induced diarrhea (for > or = 6 months after primary immunization), and a single booster immunization extended the duration of protective immunity by at least 4 months. Furthermore, MucoRice-CTB vaccination prevented diarrhea in the event of V. cholerae and LT-ETEC challenges. Thus, MucoRice-CTB is an effective long-term cold chain-free oral vaccine that induces CTB-specific SIgA-mediated longstanding protection against V. cholerae- or LT-ETEC-induced diarrhea.
Tokuhara
Daisuke
D
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Yuki
Yoshikazu
Y
Nochi
Tomonori
T
Kodama
Toshio
T
Mejima
Mio
M
Kurokawa
Shiho
S
Takahashi
Yuko
Y
Nanno
Masanobu
M
Nakanishi
Ushio
U
Takaiwa
Fumio
F
Honda
Takeshi
T
Kiyono
Hiroshi
H
D000284:Administration, Oral; D000818:Animals; D002772:Cholera Toxin / Q000276:immunology; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000276:immunology*; D056738:Cross Protection / Q000276:immunology; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006358:Hot Temperature; D007109:Immunity / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012275:Oryza / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D014611:Vaccination; D014734:Vibrio cholerae / Q000276:immunology*
D022121:Cholera Vaccines; D004768:Enterotoxins; D022361:Escherichia coli Vaccines; D007071:Immunoglobulin A, Secretory; D011971:Receptors, Immunologic; D002772:Cholera Toxin