is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant strains synthesizing nontoxic mutated α-hemolysins (Hla). The results from animal clinical trials showed that recombinant can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer's patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against pulmonary infection and significantly reduced the abscess size in a skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by . Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for .