biostudies-literatureJuarez-Rodriguez MDNIAID NIH HHS798-814https://www.ebi.ac.uk/biostudies/studies/S-EPMC3264309biostudies-literatureUnknown80(2)Tuberculosis remains a global health threat, and there is dire need to develop a vaccine that is safe and efficacious and confers long-lasting protection. In this study, we constructed recombinant attenuated Salmonella vaccine (RASV) strains with plasmids expressing fusion proteins consisting of the 80 amino-terminal amino acids of the type 3 secretion system effector SopE of Salmonella and the Mycobacterium tuberculosis antigens early secreted antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10). We demonstrated that the SopE-mycobacterial antigen fusion proteins were translocated into the cytoplasm of INT-407 cells in cell culture assays. Oral immunization of mice with RASV strains synthesizing SopE-ESAT-6-CFP-10 fusion proteins resulted in significant protection of the mice against aerosol challenge with M. tuberculosis H37Rv that was similar to the protection afforded by immunization with Mycobacterium bovis bacillus Calmette-Guérin (BCG) administered subcutaneously. In addition, oral immunization with the RASV strains specifying these mycobacterial antigens elicited production of significant antibody titers to ESAT-6 and production of ESAT-6- or CFP-10-specific gamma interferon (IFN-?)-secreting and tumor necrosis factor alpha (TNF-?)-secreting splenocytes.Infection and immunityLive attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system.PMC3264309R01 AI056289AI 56289Clark-Curtiss JEArteaga-Cortes LTKader RJuarez-Rodriguez MDCurtiss RfalseLive attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system.Tuberculosis remains a global health threat, and there is dire need to develop a vaccine that is safe and efficacious and confers long-lasting protection. In this study, we constructed recombinant attenuated Salmonella vaccine (RASV) strains with plasmids expressing fusion proteins consisting of the 80 amino-terminal amino acids of the type 3 secretion system effector SopE of Salmonella and the Mycobacterium tuberculosis antigens early secreted antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10). We demonstrated that the SopE-mycobacterial antigen fusion proteins were translocated into the cytoplasm of INT-407 cells in cell culture assays. Oral immunization of mice with RASV strains synthesizing SopE-ESAT-6-CFP-10 fusion proteins resulted in significant protection of the mice against aerosol challenge with M. tuberculosis H37Rv that was similar to the protection afforded by immunization with Mycobacterium bovis bacillus Calmette-Guérin (BCG) administered subcutaneously. In addition, oral immunization with the RASV strains specifying these mycobacterial antigens elicited production of significant antibody titers to ESAT-6 and production of ESAT-6- or CFP-10-specific gamma interferon (IFN-?)-secreting and tumor necrosis factor alpha (TNF-?)-secreting splenocytes.2012-01-01T00:00:00Z2012 Feb2021-02-21T00:16:14Z2019-03-27T00:48:20ZS-EPMC32643092214448610.1128/IAI.05525-1110.1128/iai.05525-11