Effect of Different Adjuvants on Protection and Side-Effects Induced by Helicobacter suis Whole-Cell Lysate Vaccination

• Published in: PloS one 2015-06, Vol.10 (6), p.e0131364-e0131364
• Main Authors: Bosschem, Iris, Bayry, Jagadeesh, De Bruyne, Ellen, Van Deun, Kim, Smet, Annemieke, Vercauteren, Griet, Ducatelle, Richard, Haesebrouck, Freddy, Flahou, Bram
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - adverse effects; Adjuvants, Immunologic - pharmacology; Allergology; Animals; Antigens; Bacteria; Bacterial infections; Bacterial Vaccines - adverse effects; Bacterial Vaccines - immunology; Bacterial Vaccines - pharmacology; Bacteriology; Cell migration; Cell Movement - drug effects; Cell Movement - immunology; Chemokines; Cholera; Cholera toxin; Colonization; CpG islands; Cytokines - immunology; Deoxyribonucleic acid; DNA; DNA vaccines; Female; Gastritis; Gastroenterology; Gene expression; Helicobacter heilmannii - immunology; Helicobacter Infections - immunology; Helicobacter Infections - pathology; Helicobacter Infections - prevention & control; Helicobacter pylori; Helicobacter suis; Hogs; Immunization; Immunology; Immunoregulation; Infections; Innate immunity; Interleukin 10; Interleukin 17; Interleukin 4; Life Sciences; Lymphocytes; Lymphocytes T; Metaplasia; Mice; Mice, Inbred BALB C; Mortality; Oral administration; Pathology; Protected animals; Public health; Receptors, CCR4 - antagonists & inhibitors; Receptors, CCR4 - immunology; RNA; Side effects; Stomach; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Vaccination; Vaccines; Veterinary medicine; Waterborne diseases; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131364

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.