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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

Relative gene expression in the stomach in challenged animals after immunization or after sham inoculation in study 2.The first bar represents the pooled data of negative control animals that were sham-immunized with HBSS and remained unchallenged (Neg. con). The second bar represents positive control group where mice were sham-immunized with HBSS (intranasally and subcutaneously) and were subsequently infected with H. suis (Pos. con). Bars 3 and 4 represent Cholera Toxin groups immunized intranasally (CT/lysate/IN) or sublingual routes (CT/lysate/SL) and challenged with H. suis. Bar 5 represents Freund’s complete adjuvant group (FC/lysate/SC). Bars 6 to 8 denote CCR4 antagonists group immunized by intranasal (IN), sublingual (SL) or subcutaneous (SC) routes respectively followed by challenge with H. suis. The letter ‘a’ indicates a significant (p<0.05) difference of mRNA expression levels compared to positive control groups. The letter ‘b’ indicates significant (p<0.05) changes of expression levels compared to the negative control groups.
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pone.0131364.g009: Relative gene expression in the stomach in challenged animals after immunization or after sham inoculation in study 2.The first bar represents the pooled data of negative control animals that were sham-immunized with HBSS and remained unchallenged (Neg. con). The second bar represents positive control group where mice were sham-immunized with HBSS (intranasally and subcutaneously) and were subsequently infected with H. suis (Pos. con). Bars 3 and 4 represent Cholera Toxin groups immunized intranasally (CT/lysate/IN) or sublingual routes (CT/lysate/SL) and challenged with H. suis. Bar 5 represents Freund’s complete adjuvant group (FC/lysate/SC). Bars 6 to 8 denote CCR4 antagonists group immunized by intranasal (IN), sublingual (SL) or subcutaneous (SC) routes respectively followed by challenge with H. suis. The letter ‘a’ indicates a significant (p<0.05) difference of mRNA expression levels compared to positive control groups. The letter ‘b’ indicates significant (p<0.05) changes of expression levels compared to the negative control groups.

Mentions: Similar results were obtained in the second study (Fig 9). IL-10 expression was clearly lower in all vaccinated groups as compared to positive control groups. Of note, the use of the CCR4 antagonist by the subcutaneous route induced highest IFN-γ responses confirming the previous results obtained with this adjuvant in other models where cellular immune responses were significantly induced [21,25]. However, Th1 responses were not induced when the CCR4 antagonist was used for mucosal immunization, a protocol which was shown not to be able to confer protection upon challenge with H. suis. (Fig 9. Relative gene expression in the stomach in challenged animals after immunization or after sham inoculation in study 2)


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)

Relative gene expression in the stomach in challenged animals after immunization or after sham inoculation in study 2.The first bar represents the pooled data of negative control animals that were sham-immunized with HBSS and remained unchallenged (Neg. con). The second bar represents positive control group where mice were sham-immunized with HBSS (intranasally and subcutaneously) and were subsequently infected with H. suis (Pos. con). Bars 3 and 4 represent Cholera Toxin groups immunized intranasally (CT/lysate/IN) or sublingual routes (CT/lysate/SL) and challenged with H. suis. Bar 5 represents Freund’s complete adjuvant group (FC/lysate/SC). Bars 6 to 8 denote CCR4 antagonists group immunized by intranasal (IN), sublingual (SL) or subcutaneous (SC) routes respectively followed by challenge with H. suis. The letter ‘a’ indicates a significant (p<0.05) difference of mRNA expression levels compared to positive control groups. The letter ‘b’ indicates significant (p<0.05) changes of expression levels compared to the negative control groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131364.g009: Relative gene expression in the stomach in challenged animals after immunization or after sham inoculation in study 2.The first bar represents the pooled data of negative control animals that were sham-immunized with HBSS and remained unchallenged (Neg. con). The second bar represents positive control group where mice were sham-immunized with HBSS (intranasally and subcutaneously) and were subsequently infected with H. suis (Pos. con). Bars 3 and 4 represent Cholera Toxin groups immunized intranasally (CT/lysate/IN) or sublingual routes (CT/lysate/SL) and challenged with H. suis. Bar 5 represents Freund’s complete adjuvant group (FC/lysate/SC). Bars 6 to 8 denote CCR4 antagonists group immunized by intranasal (IN), sublingual (SL) or subcutaneous (SC) routes respectively followed by challenge with H. suis. The letter ‘a’ indicates a significant (p<0.05) difference of mRNA expression levels compared to positive control groups. The letter ‘b’ indicates significant (p<0.05) changes of expression levels compared to the negative control groups.
Mentions: Similar results were obtained in the second study (Fig 9). IL-10 expression was clearly lower in all vaccinated groups as compared to positive control groups. Of note, the use of the CCR4 antagonist by the subcutaneous route induced highest IFN-γ responses confirming the previous results obtained with this adjuvant in other models where cellular immune responses were significantly induced [21,25]. However, Th1 responses were not induced when the CCR4 antagonist was used for mucosal immunization, a protocol which was shown not to be able to confer protection upon challenge with H. suis. (Fig 9. Relative gene expression in the stomach in challenged animals after immunization or after sham inoculation in study 2)

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