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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 different adjuvants on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 1.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC), Freund’s incomplete (FIC) or Curdlan (Curd) 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), CpG-DNA (CpG) or Curdlan (Curd) and applying this mixture on the external nares of the mice. Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The bacterial load is illustrated as log(10) of H. suis copies/mg stomach tissue. Individual mice are illustrated as dots. Significant differences between immunized and non-immunized challenged animals are noted by * (p<0.05). (con: uninfected, inf: infected).
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pone.0131364.g002: The protective efficacy of different adjuvants on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 1.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC), Freund’s incomplete (FIC) or Curdlan (Curd) 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), CpG-DNA (CpG) or Curdlan (Curd) and applying this mixture on the external nares of the mice. Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The bacterial load is illustrated as log(10) of H. suis copies/mg stomach tissue. Individual mice are illustrated as dots. Significant differences between immunized and non-immunized challenged animals are noted by * (p<0.05). (con: uninfected, inf: infected).

Mentions: In the first study, all immunization strategies with various adjuvants and routes of immunization (i.e. subcutaneous immunization with FC, FIC, Curdlan or intranasal immunization with CT, CpG and Curdlan) resulted in the reduction of bacterial burden following H. suis challenge, when compared to the sham-immunized/challenged animals (Fig 2). However, striking differences were observed among various adjuvants in their capacity to decrease the amount of colonizing H. suis bacteria. Subcutaneous FC/lysate (p<0.05) administration and intranasal CT/lysate (p<0.001) administration were the only to induce significant protection. (Fig 2. The protective efficacy of different adjuvants on the amount of colonizing H. suis bacteria, 3 weeks after challenge in study 1)


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 different adjuvants on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 1.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC), Freund’s incomplete (FIC) or Curdlan (Curd) 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), CpG-DNA (CpG) or Curdlan (Curd) and applying this mixture on the external nares of the mice. Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The bacterial load is illustrated as log(10) of H. suis copies/mg stomach tissue. Individual mice are illustrated as dots. Significant differences between immunized and non-immunized challenged animals are noted by * (p<0.05). (con: uninfected, inf: infected).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131364.g002: The protective efficacy of different adjuvants on the amount of colonizing H. suis bacteria, 3 weeks after challenge, in study 1.Subcutaneous immunization (SC) was done by mixing H. suis sonicate with Freund’s complete (FC), Freund’s incomplete (FIC) or Curdlan (Curd) 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), CpG-DNA (CpG) or Curdlan (Curd) and applying this mixture on the external nares of the mice. Animals in the control groups were sham-immunized with Hank’s Balanced Salt Solution (HBSS). The bacterial load is illustrated as log(10) of H. suis copies/mg stomach tissue. Individual mice are illustrated as dots. Significant differences between immunized and non-immunized challenged animals are noted by * (p<0.05). (con: uninfected, inf: infected).
Mentions: In the first study, all immunization strategies with various adjuvants and routes of immunization (i.e. subcutaneous immunization with FC, FIC, Curdlan or intranasal immunization with CT, CpG and Curdlan) resulted in the reduction of bacterial burden following H. suis challenge, when compared to the sham-immunized/challenged animals (Fig 2). However, striking differences were observed among various adjuvants in their capacity to decrease the amount of colonizing H. suis bacteria. Subcutaneous FC/lysate (p<0.05) administration and intranasal CT/lysate (p<0.001) administration were the only to induce significant protection. (Fig 2. The protective efficacy of different adjuvants on the amount of colonizing H. suis bacteria, 3 weeks after challenge in study 1)

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