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.
Highlights
Helicobacter suis (H. suis) is a Gram-negative, spiral-shaped bacterium and a worldwide spread pathogen colonizing the stomach of up to 90% of slaughter pigs
We showed that intranasal immunization, with a Cholera toxin (CT)/H. suis lysate vaccine, induced a partial protection against subsequent H. suis challenge, with some animals even doi:10.1371/journal.pone.0131364.g009
Animals were immunized subcutaneously using a H. suis lysate/saponin-based adjuvant vaccine, which clearly was shown to be inferior to the intranasal immunization protocol, with regards to its capacity to protect against a subsequent H. suis challenge [18]
Summary
Helicobacter suis (H. suis) is a Gram-negative, spiral-shaped bacterium and a worldwide spread pathogen colonizing the stomach of up to 90% of slaughter pigs. Even higher colonization rates are observed in adult boars and sows [1]. Infection with H. suis causes gastritis and a decrease in daily weight gain [2]. Several studies attribute a role to this pathogen in the development of gastric ulcer disease in pigs [2]. Economic losses due to the stomach ulcerations are believed to be substantial [3]. Infection in human patients has been associated with gastritis, peptic ulceration and mucosa associated lymphoid tissue lymphoma [3]
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