Live attenuated Salmonella-based Vaccines delivering SaEsxA by Type III Secretion System Confer Protection against Staphylococcus aureus Infection

Abstract

Staphylococcus cause a wide range of infection diseases in human and animals. The emergence of antibiotic-resistant strains promote novel strategies for prophylactic vaccine development. In this study, live attenuated Salmonella based vaccine against Staphylococcus aureus infection was developed, in which Salmonella Pathogenesis Island-1 Type 3 Secretion System (SPI-1 T3SS) was employed to deliver SaEsxA, one of ESAT-6-like (Early Secreted Antigenic Target-6) virulence factors of S. aureus. Through fusing with the N-terminal secretion and translocation domain of SPI-1 effector SipA, expression and translocation of SaEsxA into the cytosol of macrophages was detected in vitro. Oral administration of Salmonella-SaEsxA vaccine to BalB/c mice significantly induced SaEsxA-specific mucosal and humoral immune responses, detected by ELISA. Besides, Th1- and Th17- biased cellular immune response was also observed by ELISPOT assay. This multifaceted immune responses further increased the survival rate to 50% for vaccinated mice when challenged with S. aureus Newman strain, whereas all mice in control group died. Thus, the newly developed Salmonella based vaccine delivering SaEsxA by SPI-1 T3SS could confer protection against S. aureus infection. This study provides preclinical data supporting the use of Salmonella SPI-1 T3SS to translocate foreign antigens into the cytosol of antigen presenting cells to induce potent immunity against pathogens.