Novel use of anaerobically induced promoter, dmsA, for controlled expression of fragment C of tetanus toxin in live attenuated Salmonella enterica serovar Typhi strain …

N Orr, JE Galen, MM Levine - Vaccine, 2001 - Elsevier
N Orr, JE Galen, MM Levine
Vaccine, 2001Elsevier
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 …
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=55 384) 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. PdmsA derivatives are attractive promoters for in vivo expression of foreign genes in attenuated live vector vaccines.
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