Abstract
The advent of molecular biological techniques coupled with the availability of in vivo and in vitro models for studying virulence has significantly contributed to our understanding of salmonella pathogenesis. Genes and gene clusters have been identified which are known to be required for in vivo growth and survival but other genes that are necessary for the expression of full virulence by pathogenic salmonellae have still to be identified. Salmonella strains harbouring fully defined mutations have been constructed and are under evaluation in systems such as the murine typhoid model. Some of these attenuated derivatives are excellent candidate vaccine strains, eliciting potent local and systemic responses in the host. Fully genetically defined strains are now being evaluated in humans as candidate oral typhoid vaccines. Because such live vaccine strains are capable of eliciting potent immune responses they have been considered as carriers for delivering heterologous antigens to the mammalian immune system. Problems have been encountered with this approach, a major obstacle being the instability of expression of foreign antigens from recombinant plasmids. We are tackling this by utilising promotors to direct the expression of heterologous sequences that are tightly regulated but switch on in particular environments within host tissue We have demonstrated the utility of such an approach by using the nirB promotor to control the expression of heterologous antigens and have shown that this may be a generally applicable approach to obtaining the stable in vivo expression of heterologous antigens in salmonella vaccine strains.
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Dougan, G. et al. (1993). The Genetics of Salmonella and Vaccine Development. In: Cabello, F., Hormaeche, C., Mastroeni, P., Bonina, L. (eds) Biology of Salmonella . NATO ASI Series, vol 245. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2854-8_34
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DOI: https://doi.org/10.1007/978-1-4615-2854-8_34
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