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

22 Citations (Scopus)

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

Fingerprint

DNA Vaccines
Salmonella enterica
operator regions
recombinant vaccines
titration
tuberculosis
mouth
plasmids
Tuberculosis
Plasmids
Salmonella
Oral Tuberculosis
Tuberculosis Vaccines
vector vaccines
Bacterial Load
phagocytes
Mycobacterium tuberculosis
Phagocytes
fluorescence microscopy
Fluorescence Microscopy

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

Cite this

Huang, J. M., Sali, M., Leckenby, M. W., Radford, D. S., Huynh, H. A., Delogu, G., ... 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

Oral delivery of a DNA vaccine against tuberculosis using operator-repressor titration in a Salmonella enterica vector. / Huang, Jen Min; Sali, Michela; Leckenby, Matthew W.; Radford, David S.; Huynh, Hong A.; Delogu, Giovanni; Cranenburgh, Rocky M.; Cutting, Simon M.

In: Vaccine, Vol. 28, No. 47, 03.11.2010, p. 7523-7528.

Research output: Contribution to journalArticle

Huang, JM, Sali, M, Leckenby, MW, Radford, DS, Huynh, HA, Delogu, G, Cranenburgh, RM & Cutting, SM 2010, 'Oral delivery of a DNA vaccine against tuberculosis using operator-repressor titration in a Salmonella enterica vector', Vaccine, vol. 28, no. 47, pp. 7523-7528. https://doi.org/10.1016/j.vaccine.2010.09.001
Huang, Jen Min ; Sali, Michela ; Leckenby, Matthew W. ; Radford, David S. ; Huynh, Hong A. ; Delogu, Giovanni ; Cranenburgh, Rocky M. ; Cutting, Simon M. / Oral delivery of a DNA vaccine against tuberculosis using operator-repressor titration in a Salmonella enterica vector. In: Vaccine. 2010 ; Vol. 28, No. 47. pp. 7523-7528.
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