title: Genital antibody responses in mice after intranasal infection with an attenuated candidate vector strain of Bordetella pertussis.
abstract: Intranasal administration of live attenuated Bordetella pertussis, from which the pertussis toxin gene has been deleted, has previously been shown to give rise to high levels of serum immunoglobulin G (IgG) antibodies against both the protective antigen filamentous hemagglutinin (FHA) and heterologous antigens genetically fused to FHA. Here, we extend these results by demonstrating that anti-FHA IgA and IgG antibodies are also produced in the genital tract of mice, both in the vagina and in the uterus, after a single intranasal administration of B. pertussis. By comparing the immune responses induced after infection with wild-type virulent B. pertussis with that induced by infection with an attenuated pertussis toxin-deficient strain, we conclude that pertussis toxin produced by the virulent bacteria does not modify antibody production to FHA in the genital tract of B. pertussis-infected mice. The intranasal infection with either the attenuated or the virulent B. pertussis strain also led to the development of immunologic memory that could be efficiently boosted with purified FHA administered either intranasally or intravaginally to give rise to a significant increase in the levels of specific IgA and IgG produced locally in the genital tract, as well as of specific antibodies in the serum. These observations suggest that attenuated B. pertussis could be a promising vector for intranasal administration to induce antibody responses against antigens from sexually transmitted pathogens fused to FHA.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Göteborg, Göteborg, Sweden. nathalie.mielcarek@microbio.gu.se
authors.forename: N
authors.initials: N
authors.lastname: Mielcarek
authors.forename: I
authors.initials: I
authors.lastname: Nordström
authors.forename: F D
authors.initials: FD
authors.lastname: Menozzi
authors.forename: C
authors.initials: C
authors.lastname: Locht
authors.forename: J
authors.initials: J
authors.lastname: Holmgren
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001886:Bordetella pertussis / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000276:immunology*; D010566:Virulence Factors, Bordetella
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D006388:Hemagglutinins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis