title: A recombinant live attenuated strain of Vibrio cholerae induces immunity against tetanus toxin and Bordetella pertussis tracheal colonization factor.
abstract: 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.
authors.affiliation: IRIS, Chiron Vaccines Immunobiological Research Institute in Siena, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Chen
authors.forename: T M
authors.initials: TM
authors.lastname: Finn
authors.forename: L
authors.initials: L
authors.lastname: Yanqing
authors.forename: Q
authors.initials: Q
authors.lastname: Guoming
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: M
authors.initials: M
authors.lastname: Pizza
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology*; D014734:Vibrio cholerae / Q000235:genetics*; D010566:Virulence Factors, Bordetella
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013744:Tetanus Toxin; D010566:Virulence Factors, Bordetella; C040635:tetanus toxin fragment C; C096309:tracheal colonization factor, Bordetella pertussis