Current status of cholera and rise of novel mucosal vaccine.

Three serious cholera epidemics have threatened the world during the last 10 years. As a countermeasure against such cholera epidemics, three vaccines, CVD 103-HgR, WC/rBS, and Vietnamese WC, showed good performance. CVD 103-HgR is a recombinant attenuated live vaccine for travelers, and its highly safety and protective efficacy have been demonstrated in volunteers in advanced countries. WC/rBS, which consists of heat- and formalin-killed bacteria and cholera toxin B subunit, protects the vaccinees (>5 years old) from cholera for 6 months. Vietnamese WC, a heat- and formalin-killed vaccine, is inexpensive and effective even for 1 to 5-year-old children. Additionally, irradiated WC vaccines and new serotype (O139) vaccines are being developed. Regarding intestinal immunity, secretory IgA has been mainly examined. In addition, mucosal IgG, as induced by the irradiated WC vaccine, should also be investigated. Development of mucosal adjuvant, such as holotoxin-type mutants of cholera toxin and related Escherichia coli heat-labile enterotoxin, has been actively undertaken. Diverse custom-made vaccines may be one countermeasure for the changing situations in endemic countries or areas and for "barriers" against live vaccines in such areas.