A RECOMBINANT LIVE ATTENUATED STRAIN OF VIBRIO-CHOLERAE INDUCES IMMUNITY AGAINST TETANUS TOXIN AND BORDETELLA-PERTUSSIS TRACHEAL COLONIZATION FACTOR

An attenuated strain of Vibro cholerae was used as a carrier for the e xpression of heterologous antigens such as fragment C from tetanus tox in (TetC) and tracheal colonization factor from Bordetella pertussis ( Tcf). In vitro, high levels of protein were obtained when the Escheric hia coli nirB promoter was used and the bacteria were grown with low a eration. Intranasal immunization of mice with IEM101 expressing TetC e licited serum vibriocidal activity and induced antibodies against teta nus toxin which were protective against lethal challenge with 10 times the 50% lethal dose of tetanus toxin. Bacterial viability was essenti al for the induction of anti-TetC antibodies. Intranasal administratio n of IEM101 expressing Tcf induced a significant reduction in bacteria l colonization of the tracheas of mice challenged with wild-type B. pe rtussis. These data are in agreement with the putative role of Tcf in Bordetella tracheal colonization. In conclusion, we have demonstrated that V. cholerae may be used as a live vector to deliver heterologous antigens in vivo and that protection to both systemic and local challe nge may be achieved.