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Abstract

Disclosed are bacteria having virulence attenuated by a mutation to the regulatory gene poxR. Also disclosed is a method of producing bacteria having virulence attenuated by mutating to the regulatory gene poxR. Such bacteria are useful for inducing an immune response in an animal or human against virulent forms of the bacteria with reduced risk of a virulent infection. Such bacteria are also useful to allow use of normally virulent bacteria as research tools with reduced risk of virulent infection. In a preferred embodiment, poxR attenuated bacteria can be used as a vaccine to induce immunoprotection in an animal against virulent forms of the bacteria. The disclosed bacteria can also be used as hosts for the expression of heterologous genes and proteins or to deliver DNA for genetic immunization. Attenuated bacteria with such expression can be used, for example, to deliver and present heterologous antigens to the immune system of an animal. Such presentation on live bacteria can lead to improved stimulation of an immune response by the animal to the antigens. It has been discovered that bacteria harboring a poxR mutation has significantly reduced virulence. Also disclosed is the nucleotide sequence of the poxR gene from Salmonella typhimurium, and the amino acid sequence of the encoded protein. The encoded protein has 325 amino acids and has significant sequence similarity to previously uncharacterized open reading frames in E. coli and Haemophilus influenzae.

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First Claim