Oral delivery of a DNA vaccine against tuberculosis using operator-repressor titration in a Salmonella enterica vector

Jen Min Huang, Michela Sali, Matthew W. Leckenby, David S. Radford, Hong A. Huynh, Giovanni Delogu, Rocky M. Cranenburgh, Simon M. Cutting

Research output: Contribution to journalArticle

Abstract

Attenuated Salmonella enterica offers a vaccine delivery route that has the benefits of enhanced immunogenicity and oral delivery. The majority of immunization studies have been conducted to deliver recombinant proteins, expressed from a gene that is either chromosomally integrated or carried on a low- or medium-copy number plasmid. There are, however, an increasing number of reports demonstrating the delivery of DNA vaccines, but the high-copy number plasmids that are preferentially used for this application are unstable in Salmonella. Here, we use the Operator-Repressor Titration (ORT) plasmid maintenance system in Salmonella enterica serovar Typhimurium to deliver a high-copy number plasmid expressing the Mycobacterium tuberculosis gene mpt64 to mice. MPT64 expression was detected in phagocytes using immunofluorescence microscopy following Salmonella-mediated delivery of the DNA vaccine. The indicative CD8+ responses measured by antigen-specific IFN-γ were higher from the live bacterial vector than from injected plasmid DNA, and a reduction in the pulmonary bacterial load was seen following an aerogenic challenge. This illustrates the potential of live attenuated Salmonella as oral tuberculosis vaccine vectors.

Original languageEnglish
Pages (from-to)7523-7528
Number of pages6
JournalVaccine
Volume28
Issue number47
DOIs
Publication statusPublished - Nov 3 2010

Keywords

  • DNA vaccine
  • M. tuberculosis
  • Oral vaccine
  • Salmonella enterica

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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  • Cite this

    Huang, J. M., Sali, M., Leckenby, M. W., Radford, D. S., Huynh, H. A., Delogu, G., Cranenburgh, R. M., & Cutting, S. M. (2010). Oral delivery of a DNA vaccine against tuberculosis using operator-repressor titration in a Salmonella enterica vector. Vaccine, 28(47), 7523-7528. https://doi.org/10.1016/j.vaccine.2010.09.001