Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein

Lindsay J. Hall, Simon Clare, Derek Pickard, Simon O. Clark, Dominic L.F. Kelly, Moataz Abd El Ghany, Christine Hale, Jes Dietrich, Peter Andersen, Philip D. Marsh, Gordon Dougan

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 TH1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.

Original languageEnglish
Pages (from-to)6894-6904
Number of pages11
JournalVaccine
Volume27
Issue number49
DOIs
Publication statusPublished - 16 Nov 2009
Externally publishedYes

Keywords

  • M. tuberculosis
  • Mucosal vaccine
  • Salmonella vector

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