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

Michela Sali, Giovanni Delogu, J Huang, Mw Leckenby, Ds Radford, Ha Huynh, Rm Cranenburgh, Sm Cutting

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

24 Citazioni (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.
Lingua originaleEnglish
pagine (da-a)7523-7528
Numero di pagine6
RivistaVACCINE
Volume28
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Administration, Oral
  • Animals
  • Antigens, Bacterial
  • Bacterial Load
  • CD8-Positive T-Lymphocytes
  • Cell Line
  • Epitopes, T-Lymphocyte
  • Female
  • Genetic Vectors
  • Immunity, Cellular
  • Interferon-gamma
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phagocytes
  • Plasmids
  • Salmonella enterica
  • Tuberculosis
  • Tuberculosis Vaccines
  • Vaccines, Attenuated
  • Vaccines, DNA

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