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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

The protective efficacy of the different immunization protocols on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 2.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC) or the CCR4 antagonist (CCR4) and injecting this mixture at the lower back of the mice. Intranasal immunization (IN) was done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4 antagonist (CCR4) and applying this mixture on the external nares of the mice. Sublingual immunizations (SL) were done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4-antagonist (CCR4). Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The amount of bacteria colonizing the stomach of the mice are illustrated as log(10) of H. suis copies/mg stomach. The individual animals are presented as dots. Significant differences between the immunized and challenged groups and the positive control group are noted by ** (p<0.01) and *** (p<0.001). (neg. con.: sham-immunized/not challenged, pos. con.: sham-immunized/challenged).
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pone.0131364.g003: The protective efficacy of the different immunization protocols on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 2.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC) or the CCR4 antagonist (CCR4) and injecting this mixture at the lower back of the mice. Intranasal immunization (IN) was done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4 antagonist (CCR4) and applying this mixture on the external nares of the mice. Sublingual immunizations (SL) were done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4-antagonist (CCR4). Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The amount of bacteria colonizing the stomach of the mice are illustrated as log(10) of H. suis copies/mg stomach. The individual animals are presented as dots. Significant differences between the immunized and challenged groups and the positive control group are noted by ** (p<0.01) and *** (p<0.001). (neg. con.: sham-immunized/not challenged, pos. con.: sham-immunized/challenged).

Mentions: The results obtained with CT/lysate were also confirmed in the second study, wherein the intranasal as well as sublingual route of immunization conferred the highest protection against colonization of H. suis in the stomach (P<0.001) (Fig 3). In addition, animals subcutaneously immunized with FC/lysate and CCR4 antagonist/lysate showed significantly lower H. suis colonization levels after experimental challenge (P<0.01). In contrast, mucosal immunization with CCR4 antagonists (both intranasally and sublingually) and lysate showed no significant decrease in bacteria colonizing the stomach. Colonization levels in animals that were administrated the CCR4 antagonist in the absence of lysate and that were subsequently challenged, were similar to those in the sham-immunized and challenged positive control animals. (Fig 3. The protective efficacy of the different immunization protocols on the amount of colonizing H. suis bacteria, 3 weeks after challenge 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)

The protective efficacy of the different immunization protocols on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 2.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC) or the CCR4 antagonist (CCR4) and injecting this mixture at the lower back of the mice. Intranasal immunization (IN) was done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4 antagonist (CCR4) and applying this mixture on the external nares of the mice. Sublingual immunizations (SL) were done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4-antagonist (CCR4). Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The amount of bacteria colonizing the stomach of the mice are illustrated as log(10) of H. suis copies/mg stomach. The individual animals are presented as dots. Significant differences between the immunized and challenged groups and the positive control group are noted by ** (p<0.01) and *** (p<0.001). (neg. con.: sham-immunized/not challenged, pos. con.: sham-immunized/challenged).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131364.g003: The protective efficacy of the different immunization protocols on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 2.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC) or the CCR4 antagonist (CCR4) and injecting this mixture at the lower back of the mice. Intranasal immunization (IN) was done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4 antagonist (CCR4) and applying this mixture on the external nares of the mice. Sublingual immunizations (SL) were done by mixing H. suis sonicate with Cholera toxin (CT) or the CCR4-antagonist (CCR4). Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The amount of bacteria colonizing the stomach of the mice are illustrated as log(10) of H. suis copies/mg stomach. The individual animals are presented as dots. Significant differences between the immunized and challenged groups and the positive control group are noted by ** (p<0.01) and *** (p<0.001). (neg. con.: sham-immunized/not challenged, pos. con.: sham-immunized/challenged).
Mentions: The results obtained with CT/lysate were also confirmed in the second study, wherein the intranasal as well as sublingual route of immunization conferred the highest protection against colonization of H. suis in the stomach (P<0.001) (Fig 3). In addition, animals subcutaneously immunized with FC/lysate and CCR4 antagonist/lysate showed significantly lower H. suis colonization levels after experimental challenge (P<0.01). In contrast, mucosal immunization with CCR4 antagonists (both intranasally and sublingually) and lysate showed no significant decrease in bacteria colonizing the stomach. Colonization levels in animals that were administrated the CCR4 antagonist in the absence of lysate and that were subsequently challenged, were similar to those in the sham-immunized and challenged positive control animals. (Fig 3. The protective efficacy of the different immunization protocols on the amount of colonizing H. suis bacteria, 3 weeks after challenge 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