Yersinia pestis PsaA is an adhesin that is synthesized inside macrophages. Here, we evaluated the immune profile of codon-optimized Y. pestis PsaA synthesized in a live recombinant attenuated Salmonella vaccine (RASV) strain chi9558. Oral immunization of BALB/c mice with chi9558(pYA3705) delivering a secreted form of PsaA, elicited a systemic PsaA-specific immunoglobulin G (IgG) response but offered limited protection against lethal challenge with the intranasally introduced Y. pestis CO92 strain. Our results suggest that appropriate fine-tuning of Y. pestis PsaA delivery by RASV could improve its protective role in curtailing plague colonization and infection.