Protection against murine listeriosis by oral vaccination with recombinantSalmonella expressing hybrid Yersinia type III proteins

In the present study, we have investigated the possibility to engage the Ye rsinia outer protein E (YopE) as a carrier molecule for heterologous Ag del ivery by the type III secretion system of Salmonella typhimurium. Defined s ecretion and translocation domains of YopE were fused to the immunodominant T cell Ags listeriolysin O and p60 of Listeria monocytogenes. In vitro exp eriments showed that S. typhimurium allows secretion and translocation of l arge hybrid YopE proteins in a type III-dependent fashion. Translocation an d cytosolic delivery of these chimeric proteins into host cells, but not se cretion into endosomal compartments, led to efficient MHC class I-restricte d Ag presentation of listerial nonamer peptides. Mice orally vaccinated wit h a single dose of attenuated S. typhimurium expressing translocated hybrid YopE proteins revealed high numbers of IFN-gamma -producing cells reactive with listeriolysin O 91-99 or p60 217-225, respectively. This CD8 T cell r esponse protected mice against a challenge with L. monocytogenes. In conclu sion, these findings suggest that YopE is a versatile carrier molecule for type III-mediated foreign Ag delivery by Salmonella vaccine strains.