Live attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system

María Dolores Juárez-Rodríguez, Lourdes T. Arteaga-Cortés, Rebin Kader, Roy Curtiss, Josephine E. Clark-Curtiss

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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-γ)-secreting and tumor necrosis factor alpha (TNF-α)-secreting splenocytes.

Original languageEnglish (US)
Pages (from-to)798-814
Number of pages17
JournalInfection and immunity
Volume80
Issue number2
DOIs
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Juárez-Rodríguez, M. D., Arteaga-Cortés, L. T., Kader, R., Curtiss, R., & Clark-Curtiss, J. E. (2012). Live attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system. Infection and immunity, 80(2), 798-814. https://doi.org/10.1128/IAI.05525-11