title: Effect of Different Adjuvants on Protection and Side-Effects Induced by Helicobacter suis Whole-Cell Lysate Vaccination.
abstract: Helicobacter suis (H. suis) is a widespread porcine gastric pathogen, which is also of zoonotic importance. The first goal of this study was to investigate the efficacy of several vaccine adjuvants (CpG-DNA, Curdlan, Freund's Complete and Incomplete, Cholera toxin), administered either subcutaneously or intranasally along with H. suis whole-cell lysate, to protect against subsequent H. suis challenge in a BALB/c infection model. Subcutaneous immunization with Freund's complete (FC)/lysate and intranasal immunization with Cholera toxin (CT)/lysate were shown to be the best options for vaccination against H. suis, as determined by the amount of colonizing H. suis bacteria in the stomach, although adverse effects such as post-immunization gastritis/pseudo-pyloric metaplasia and increased mortality were observed, respectively. Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects. A CCR4 antagonist that transiently inhibits the migration of regulatory T cells was also included as a new adjuvant in this second study. Results confirmed that immunization with CT (intranasally or sublingually) is among the most effective vaccination protocols, but increased mortality was still observed. In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed. Compared to the FC/lysate immunized group, gastric pseudo-pyloric metaplasia was less severe or even absent in the CCR4 antagonist/lysate immunized group. In general, an inverse correlation was observed between IFN-γ, IL-4, IL-17, KC, MIP-2 and LIX mRNA expression and H. suis colonization density, whereas lower IL-10 expression levels were observed in partially protected animals.
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Iris
authors.initials: I
authors.lastname: Bosschem
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1138, Paris, France; Centre de Recherche des Cordeliers, Equipe-Immunopathology and therapeutic immunointervention, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: De Bruyne
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Van Deun
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Smet
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Vercauteren
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Ducatelle
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Flahou
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018247:Helicobacter heilmannii / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; C515355:Ccr4 protein, mouse; D016207:Cytokines; D054398:Receptors, CCR4