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Vaccine. 2001 Feb 8;19(13-14):1694-700.

Novel use of anaerobically induced promoter, dmsA, for controlled expression of fragment C of tetanus toxin in live attenuated Salmonella enterica serovar Typhi strain CVD 908-htrA.

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Department of Pediatrics, University of Maryland School of Medicine, Center for Vaccine Development, 685 West Baltimore Street, Baltimore, MD 21201, USA.


The anaerobically induced promoter dmsA (PdmsA) was adapted to optimize in vivo expression of foreign antigens in attenuated Salmonella enterica serovar Typhi live vector vaccines CVD 908-htrA. PdmsA from Escherichia coli and two derivatives, PdmsA2 and PdmsA3 were cloned into a plasmid driving the expression of a gene encoding tetanus toxin fragment C. Expression of fragment C varied from a low level induced by pTETdmsA, to moderate and high levels induced, respectively, by pTETdmsA2 and pTETdmsA3. Mice were immunized intranasally with CVD 908-htrA harboring pTETdmsA2 or pTETdmsA3, and the serum antitoxin response was compared to that elicited by CVD 908-htrA(pTETnir15) (Pnir15 is a benchmark anaerobically activated promoter). S. Typhi carrying pTETdmsA2 elicited modest tetanus antitoxin titers while S. Typhi harboring pTETdmsA3 generated elevated titers (GMT=55384) that were higher than elicited by pTETnir15 (GMT=4354) (P=0.007). Mice immunized with CVD 908-htrA carrying pTETdmsA3 and pTETnir15 survived tetanus toxin challenge. P(dmsA) derivatives are attractive promoters for in vivo expression of foreign genes in attenuated live vector vaccines.

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