Secretory IgA-mediated protection against V. cholerae and heat-labile enterotoxin-producing enterotoxigenic Escherichia coli by rice-based vaccine

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-05, Vol.107 (19), p.8794-8799
• Main Authors: Tokuhara, Daisuke, Yuki, Yoshikazu, Nochi, Tomonori, Kodama, Toshio, Mejima, Mio, Kurokawa, Shiho, Takahashi, Yuko, Nanno, Masanobu, Nakanishi, Ushio, Takaiwa, Fumio, Honda, Takeshi, Kiyono, Hiroshi
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antibodies; Antigens; Biological Sciences; Cholera; Cholera Toxin - immunology; Cholera Vaccines - administration & dosage; Cholera Vaccines - immunology; Cross Protection - immunology; Diarrhea; Diarrhea - immunology; Diarrhea - microbiology; Diarrhea - prevention & control; E coli; Enterotoxigenic Escherichia coli - immunology; Enterotoxins - immunology; Escherichia coli; Escherichia coli Vaccines - administration & dosage; Escherichia coli Vaccines - immunology; Female; Gastroenterology; Gastrointestinal diseases; Hot Temperature; Immunity; Immunity - immunology; Immunization; Immunoglobulin A, Secretory - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Oryza - immunology; Receptors, Immunologic - immunology; Rice; Toxins; Vaccination; Vaccines; Vibrio cholerae; Vibrio cholerae - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0914121107

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 ≥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.