title: Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA with adjuvant monophosphoryl lipid A protects swine from a homologous but not a heterologous challenge.
abstract: Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbAI) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbAI dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HPhgbAI and 35000HPhgbAII, respectively). Pigs immunized with the nHgbAI/MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HPhgbAI but not heterologous strain 35000HPhgbAII, as evidenced by the isolation of only strain 35000HPhgbAII from nHgbAI-immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbAI-immunized animals challenged with strains 35000HPhgbAI but not those challenged with strain 35000HPhgbAII. Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbAI/MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbAI/Freund's vaccine; however, anti-nHgbAI from both studies bound whole cells of 35000HPhgbAI better than 35000HPhgbAII and partially blocked hemoglobin binding to nHgbAI. In conclusion, despite eliciting lower antibody ELISA activity than the nHgbAI/Freund's, the nHgbAI/MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi, suggesting that a bivalent HgbA vaccine may be needed.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of North Carolina, 111 Mason Farm Road, CB no. 7031, Chapel Hill, NC 27599, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Fusco
authors.forename: Galyna
authors.initials: G
authors.lastname: Afonina
authors.forename: Igor
authors.initials: I
authors.lastname: Nepluev
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Cholon
authors.forename: Neelima
authors.initials: N
authors.lastname: Choudhary
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Routh
authors.forename: Glenn W
authors.initials: GW
authors.lastname: Almond
authors.forename: Paul E
authors.initials: PE
authors.lastname: Orndorff
authors.forename: Herman
authors.initials: H
authors.lastname: Staats
authors.forename: Marcia M
authors.initials: MM
authors.lastname: Hobbs
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leduc
authors.forename: Christopher
authors.initials: C
authors.lastname: Elkins
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002602:Chancroid / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D006191:Haemophilus ducreyi / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013552:Swine
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D007106:Immune Sera; D008050:Lipid A; C017206:hemoglobin-binding protein, bacteria; C048436:monophosphoryl lipid A