Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against Trichuris muris infection

Open Biol. 2017 Apr;7(4):170031. doi: 10.1098/rsob.170031.

Abstract

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other experimental groups. Also, these animals presented significantly different chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft cells did not vary between groups, the intensity of fluorescence per cell was significant in the group immunized with the rPP2A-OVS. The results of the present study suggest that mice immunized with the lipopeptide are capable of activating a combined Th17/Th9 response. This strategy of immunization may be of great applicability not only in immunotherapy and immunoprophylaxis to control diseases caused by nematodes but also in pathologies necessitating action at the level of the Th9 response in the intestinal mucosa.

Keywords: Trichuris muris vaccination; chemokines; cytokines; lipid vinyl sulfone; self-assembling lipopeptide rPP2A.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemical synthesis
  • Administration, Intranasal
  • Amino Acid Sequence
  • Animals
  • Chemokine CCL11 / genetics
  • Chemokine CCL11 / immunology
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / immunology
  • Female
  • Gene Expression
  • Helminth Proteins / administration & dosage*
  • Helminth Proteins / biosynthesis
  • Helminth Proteins / immunology
  • Interleukins / genetics
  • Interleukins / immunology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / parasitology
  • Lipopeptides / administration & dosage*
  • Lipopeptides / biosynthesis
  • Lipopeptides / immunology
  • Mice
  • Mice, Inbred AKR
  • Parasite Egg Count
  • Protein Phosphatase 2 / administration & dosage*
  • Protein Phosphatase 2 / biosynthesis
  • Protein Phosphatase 2 / immunology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / immunology
  • Sequence Alignment
  • Sulfones / administration & dosage*
  • Sulfones / chemistry
  • Sulfones / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / parasitology
  • Trichuriasis / immunology
  • Trichuriasis / parasitology
  • Trichuriasis / prevention & control*
  • Trichuris / drug effects
  • Trichuris / immunology
  • Vaccines, Conjugate / administration & dosage*

Substances

  • Adjuvants, Immunologic
  • CCL20 protein, mouse
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Chemokine CCL20
  • Helminth Proteins
  • Interleukins
  • Lipopeptides
  • Recombinant Proteins
  • Sulfones
  • Vaccines, Conjugate
  • divinyl sulfone
  • Protein Phosphatase 2