title: High vaccine efficacy against shigellosis of recombinant noninvasive Shigella mutant that expresses Yersinia invasin.
abstract: Live attenuated Shigella vaccines elicit protective immune responses, but involve a potential risk of inducing a strong inflammatory reaction. The bacterial invasiveness that is crucial for Ag delivery causes inflammatory destruction of infected epithelial cells and proinflammatory cell death of infected macrophages. In this study, the noninvasive Shigella mutant DeltaipaB was equipped with Yersinia invasin protein, which has been shown to mediate bacterial invasion and targeting to M cells located in follicle-associated epithelium. Invasin-expressing DeltaipaB (DeltaipaB/inv) was internalized into epithelial cells and retained in the intraphagosomal space. DeltaipaB/inv did not induce necrotic cell death of infected macrophages nor cause symptomatic damage after intranasal vaccination of mice. DeltaipaB/inv was safer and more effective than the conventional live vaccine, DeltavirG. Infection by DeltaipaB/inv caused polymorphonuclear neutrophil infiltration in the lung, but did not induce production of large amounts of proinflammatory cytokines. We concluded that the low experimental morbidity and high vaccine efficacy of DeltaipaB/inv are primarily based on high protective immune responses, which may be enhanced by the polymorphonuclear neutrophil infiltration unaccompanied by tissue injury.
authors.affiliation: Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. t-suzuki@ims.u-tokyo.ac.jp
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ashida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iwai
authors.forename: Takahito
authors.initials: T
authors.lastname: Toyotome
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsui
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D004405:Dysentery, Bacillary / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012760:Shigella / Q000235:genetics / Q000276:immunology; D022281:Shigella Vaccines / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D022281:Shigella Vaccines; D014614:Vaccines, Synthetic; C053476:invasin, Yersinia