title: Oral immunization using HgbA in a recombinant chancroid vaccine delivered by attenuated Salmonella typhimurium SL3261 in the temperature-dependent rabbit model.
abstract: Chancroid, a sexually transmitted genital ulcer disease caused by the Gram-negative bacterium Haemophilus ducreyi, facilitates the acquisition and transmission of HIV. An effective vaccine against chancroid has not been developed. In this preliminary study, the gene encoding the H. ducreyi outer membrane hemoglobin receptor HgbA was cloned into the plasmid pTETnir15. The recombinant construct was introduced into the attenuated Salmonella typhimurium SL3261 strain and stable expression was induced in vitro under anaerobic conditions. The vaccine strain was delivered into the temperature-dependent rabbit model of chancroid by intragastric immunization as a single dose, or as three doses administered at two-weekly intervals. No specific antibody to HgbA was elicited after either dose schedule. Although the plasmid vector survived in vivo passage for up to 15 days following single oral challenge, HgbA expression was restricted to plasmid isolates recovered one day after immunization. Rabbits inoculated with the 3-dose booster regimen achieved no protective immunity from homologous challenge. These results emphasize that refinements in plasmid design to enhance a durable heterologous protein expression are necessary for the development of a live oral vaccine against chancroid.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.
authors.forename: Cathy
authors.initials: C
authors.lastname: Breau
authors.forename: D William
authors.initials: DW
authors.lastname: Cameron
authors.forename: Marc
authors.initials: M
authors.lastname: Desjardins
authors.forename: B Craig
authors.initials: BC
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002602:Chancroid / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D006191:Haemophilus ducreyi / Q000235:genetics / Q000276:immunology; D007114:Immunization / Q000379:methods; D008297:Male; D011817:Rabbits; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C017206:hemoglobin-binding protein, bacteria