Rational live oral carrier vaccine design by mutating virulence-associatedgenes of Yersinia enterocolitica

Three different Yersinia enterocolitica serotype O8 strains harboring mutat ions in virulence-associated genes coding for Yersinia adhesin A (YadA), Mn -cofactored superoxide dismutase (SodA), and high-molecular weight protein 1 were analyzed for their ability to colonize and persist in tissues after orogastric immunization of C57BL/6 mice. We demonstrated that all three Yer sinia mutant strains were markedly impaired in their ability to disseminate into the spleens and livers of immunized mice but were able to colonize th e Peyer's patches for at least 12 days, resulting in the induction of signi ficant antibody titers against Yersinia outer proteins (Yops) and in the pr iming of Yersinia antigen-specific CD4(+) Th1 cells isolated from spleens. The high level of attenuation did not diminish the immunogenic properties o f the mutant strains. In bet, mice immunized with a single oral dose of any of the mutant strains were protected against a lethal oral-challenge infec tion with wild-type Y. enterocolitica. Moreover, adoptive transfer of Yersi nia-specific antibodies from sera of mice immunized with the mutant WAP-314 sodA revealed that this protection could be mediated by Yersinia-specific: immunoglobulins.