The use of live recombinant Salmonella attenuated vaccine (RASV) encoding Yersinia proteins is a promising new approach for the vaccination against Yersinia pestis. We have tested the efficacy of 2 proteins, Psn and a portion of LcrV in protecting mice against virulent Yersinia pestis challenge. To remove the immunosuppressive properties of LcrV protein, the lcrV gene, without the TLR2 receptor sequence, was cloned into a β-lactamase secretion vector. Immunizations were performed with RSAV expressing LcrV or Psn. Challenge with a virulent Y. pestis strain was performed 4 weeks after the last immunization. Our results show that the truncated LcrV protein delivered by RASV is sufficient to afford a full protective immune response in a mouse model of bubonic plague and the Psn protein afforded partial protection in a non-optimized system. This finding should facilitate the design and development of a new generation of vaccines against Y. pestis.