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Infect Immun, April 1998, p. 1648-1653, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Recombinant Live Attenuated Strain of Vibrio cholerae Induces Immunity against Tetanus Toxin and Bordetella pertussis Tracheal Colonization Factor

Inês Chen,^1,2 Theresa M. Finn,³ Liu Yanqing,⁴ Qi Guoming,⁴ Rino Rappuoli,^1,* and Mariagrazia Pizza¹

IRIS, Chiron Vaccines Immunobiological Research Institute in Siena, 53100 Siena, Italy¹; Departamento de Microbiologia, ICB II, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil²; Laboratory of Pertussis, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892-0029³; and Chinese Academy of Preventive Medicine, Beijing, China⁴

Received 2 September 1997/Returned for modification 25 October 1997/Accepted 7 December 1997

An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf). In vitro, high levels of protein were obtained when the Escherichia coli nirB promoter was used and the bacteria were grown with low aeration. Intranasal immunization of mice with IEM101 expressing TetC elicited serum vibriocidal activity and induced antibodies against tetanus toxin which were protective against lethal challenge with 10 times the 50% lethal dose of tetanus toxin. Bacterial viability was essential for the induction of anti-TetC antibodies. Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. 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 challenge may be achieved.

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^* Corresponding author. Mailing address: IRIS, Chiron Vaccines Immunobiological Research Institute in Siena, Via Fiorentina, 1, 53100 Siena, Italy. Phone: 39-577-243414. Fax: 39-577-243564. E-mail: Rappuoli{at}IRIS02.BIOCINE.IT.

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