Salmonella typhi and S. typhimurium derivatives harbouring deletions in aromatic biosynthesis and Salmonella Pathogenicity Island-2 (SPI-2) genes as vaccines and vectors

Shahid A. Khan, Richard Stratford, Tao Wu, Nicola Mckelvie, Trevor Bellaby, Zoe Hindle, Katharine A. Sinha, Shayne Eltze, Piero Mastroeni, Derek Pickard, Gordon Dougan, Steven N. Chatfield, Frank R. Brennan

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49 Citations (Scopus)

Abstract

The S. typhimurium strain (TML ΔaroC ΔssaV) WT05, harbouring defined deletions in genes involved in both the aromatic biosynthesis pathway (aroC) and the Salmonella Pathogenicity Island-2 (SPI-2) (ssaV) was shown to be significantly attenuated in C57 BL/6 interferon gamma knockout mice following oral inoculation. Similarly, the S. typhi strain (Ty2 ΔaroC ΔssaV) ZH9 harbouring the aroC and ssaV mutations propagated less efficiently than wild type in human macrophages. These studies demonstrated the attractive safety profile of the aroC ssaV mutant combination. Strains S. typhimurium (TML ΔaroC ΔssaV ) WT05 and S. typhi (Ty2 ΔaroC ΔssaV) ZH9 were subsequently tested as vaccine vectors to deliver E. coli heat-labile toxin (LT-B) mucosally to mice. Mice inoculated orally with S. typhimurium (TML ΔaroC ΔssaV) WT05 expressing LT-B (WT05/LT-B) elicited high titres of both LT-specific serum IgG and intestinal IgA, although no specific IgA was detected in the vagina. Similarly, intranasal inoculation of mice with S. typhi (Ty2 ΔaroC ΔssaV) ZH9 expressing LT-B (ZH9/LT-B) elicited even higher titres of LT-specific serum antibody as well as LT-specific Ig in the vagina. We conclude that ΔaroC ΔssaV strains of Salmonella are highly attenuated and are promising candidates both as human typhoid vaccines and as vaccine vectors for the delivery of heterologous antigens.

Original languageEnglish
Pages (from-to)538-548
Number of pages11
JournalVaccine
Volume21
Issue number5-6
DOIs
Publication statusPublished - 17 Jan 2003
Externally publishedYes

Keywords

  • aroC
  • E. coli heat-labile toxin
  • Mucosal vaccination
  • S. typhi
  • S. typhimurium
  • Salmonella Pathogenicity Island-2

Cite this

Khan, S. A., Stratford, R., Wu, T., Mckelvie, N., Bellaby, T., Hindle, Z., Sinha, K. A., Eltze, S., Mastroeni, P., Pickard, D., Dougan, G., Chatfield, S. N., & Brennan, F. R. (2003). Salmonella typhi and S. typhimurium derivatives harbouring deletions in aromatic biosynthesis and Salmonella Pathogenicity Island-2 (SPI-2) genes as vaccines and vectors. Vaccine, 21(5-6), 538-548. https://doi.org/10.1016/S0264-410X(02)00410-3