title: Detoxified Haemophilus ducreyi cytolethal distending toxin and induction of toxin specific antibodies in the genital tract.
abstract: Haemophilus ducreyi causes genital ulceration (chancroid), a sexually transmitted infection and still an important factor which contributes to the spread of HIV in developing countries. The bacterium produces a cytolethal distending toxin (HdCDT) causing cell cycle arrest and apoptosis/necrosis of human cells and contributes to the aggravation of ulcers. The aim of the study was to induce toxin-neutralizing antibodies in the genital tract of mice. Repeated subcutaneous (sc) immunisations with 5-10microg active HdCDT induced low levels of serum anti-HdCDT IgG without neutralizing capacity. High levels of specific IgG1 antibodies in serum and genital tract were generated after sc immunisations with 10microg formaldehyde detoxified HdCDT toxoid alone and the addition of aluminium salts or RIBI (based on the lipid A moiety) as adjuvant further increased the level of serum antibodies. A high correlation was found between elevated levels of anti-HdCDT IgG in sera, the level of neutralizing activity and the antibody level in genital tract (r=0.8). Thus, induction of high antibody levels specific to HdCDT in the genital tissue can be achieved by parenteral immunisation with the toxoid. The HdCDT toxoid can be considered as a candidate component in vaccine against chancroid.
authors.affiliation: Institute of Biomedicine, Department of Microbiology and Immunology and MIVAC Göteborg University, Göteborg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Lundqvist
authors.forename: Julia
authors.initials: J
authors.lastname: Fernandez-Rodrigues
authors.forename: Karin
authors.initials: K
authors.lastname: Ahlman
authors.forename: Teresa
authors.initials: T
authors.lastname: Lagergård
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D002460:Cell Line; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D006191:Haemophilus ducreyi / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; C067044:cytolethal distending toxin