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

Bosschem I, Bayry J, De Bruyne E, Van Deun K, Smet A, Vercauteren G, Ducatelle R, Haesebrouck F, Flahou B - PLoS ONE (2015)

Bottom Line: Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects.In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus

H&E and PAS staining of the fundus showing pronounced inflammation and severe pseudo-pyloric metaplasia.H&E (A) and PAS staining (B) of the fundus of an animal in the FC subcutaneously immunized and challenged group, showing pronounced inflammation and severe pseudo-pyloric metaplasia (original magnification: 100x).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482594&req=5

pone.0131364.g006: H&E and PAS staining of the fundus showing pronounced inflammation and severe pseudo-pyloric metaplasia.H&E (A) and PAS staining (B) of the fundus of an animal in the FC subcutaneously immunized and challenged group, showing pronounced inflammation and severe pseudo-pyloric metaplasia (original magnification: 100x).

Mentions: Interestingly, in the first study, pseudo-pyloric metaplasia was detected in the stomach of 75% of the mice from the FC/lysate immunized and challenged group and even in 100% of the animals belonging to the FIC/lysate and SC Curdlan/lysate immunized and challenged animals. In all other groups, no pseudo-pyloric metaplasia was observed (Fig 5). In the second study, pseudo-pyloric metaplasia of the fundus was present in the group immunized with FC/lysate and CT/lysate/SL and challenged (Fig 6). Although pseudo-pyloric metaplasia was also present in the CCR4 antagonist/lysate/SC immunized and challenged group (Fig 7), this was nevertheless less severe and not present in all animals, compared to the group immunized with FC/lysate (Table 5). (Fig 5. Histopathological analysis of fundus by H&E staining, Fig 6. H&E and PAS staining of the fundus showing pronounced inflammation and severe pseudo-pyloric metaplasia, Fig 7. H&E and PAS staining of the fundus, showing mild inflammation and pseudo-pyloric metaplasia)


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

Bosschem I, Bayry J, De Bruyne E, Van Deun K, Smet A, Vercauteren G, Ducatelle R, Haesebrouck F, Flahou B - PLoS ONE (2015)

H&E and PAS staining of the fundus showing pronounced inflammation and severe pseudo-pyloric metaplasia.H&E (A) and PAS staining (B) of the fundus of an animal in the FC subcutaneously immunized and challenged group, showing pronounced inflammation and severe pseudo-pyloric metaplasia (original magnification: 100x).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482594&req=5

pone.0131364.g006: H&E and PAS staining of the fundus showing pronounced inflammation and severe pseudo-pyloric metaplasia.H&E (A) and PAS staining (B) of the fundus of an animal in the FC subcutaneously immunized and challenged group, showing pronounced inflammation and severe pseudo-pyloric metaplasia (original magnification: 100x).
Mentions: Interestingly, in the first study, pseudo-pyloric metaplasia was detected in the stomach of 75% of the mice from the FC/lysate immunized and challenged group and even in 100% of the animals belonging to the FIC/lysate and SC Curdlan/lysate immunized and challenged animals. In all other groups, no pseudo-pyloric metaplasia was observed (Fig 5). In the second study, pseudo-pyloric metaplasia of the fundus was present in the group immunized with FC/lysate and CT/lysate/SL and challenged (Fig 6). Although pseudo-pyloric metaplasia was also present in the CCR4 antagonist/lysate/SC immunized and challenged group (Fig 7), this was nevertheless less severe and not present in all animals, compared to the group immunized with FC/lysate (Table 5). (Fig 5. Histopathological analysis of fundus by H&E staining, Fig 6. H&E and PAS staining of the fundus showing pronounced inflammation and severe pseudo-pyloric metaplasia, Fig 7. H&E and PAS staining of the fundus, showing mild inflammation and pseudo-pyloric metaplasia)

Bottom Line: Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects.In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus