Intranasal delivery of a formulation containing stage-specific recombinant proteins of Fasciola hepatica cathepsin L5 and cathepsin B2 triggers an anti-fecundity effect and an adjuvant-mediated reduction in fluke burden in sheep

Vet Parasitol. 2018 Jul 15:258:14-23. doi: 10.1016/j.vetpar.2018.05.008. Epub 2018 Jun 9.

Abstract

Fasciola hepatica infection continues to be a major problem in the agriculture sector, particularly in sheep and cattle. Cathepsin L and B proteases are major components of the excretory/secretory material of the parasite, and their roles in several important aspects of parasite invasion and survival has led to their use as targets in rational vaccine design. Previous studies in rats demonstrated that the use of stage-specific antigens, cathepsin B2 and cathepsin L5, as part of a multivalent vaccine, was able to confer significant protection against challenge. In the present study, recombinant versions of cathepsin L5 and cathepsin B2 produced in yeast were used in combination to vaccinate sheep. Intramuscular and intranasal forms of administration were applied, and sheep were subsequently challenged with 150 F. hepatica metacercariae. Intramuscular vaccination was able to induce a strong systemic antibody response against both antigens, but failed to confer significant protection. Conversely, no elevated antibody response was detected against the vaccine antigens following nasal vaccination; however, a reduction in parasite egg viability (>92%) and a statistically significant (p = 0.006), predominantly adjuvant-mediated reduction in worm burdens was observed.

Keywords: Cysteine protease; Fasciola hepatica; Intranasal vaccination; Ruminant; Vaccination.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Intranasal / methods
  • Animals
  • Antibodies, Helminth / blood
  • Antigens, Helminth / immunology
  • Cathepsins / administration & dosage
  • Cathepsins / genetics
  • Cathepsins / immunology*
  • Cattle
  • Cysteine Endopeptidases / administration & dosage
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / immunology
  • Fasciola hepatica / chemistry
  • Fasciola hepatica / genetics
  • Fasciola hepatica / immunology*
  • Fertility*
  • Injections, Intramuscular
  • Parasite Egg Count
  • Parasite Load
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*
  • Sheep / immunology
  • Sheep Diseases / immunology
  • Sheep Diseases / parasitology
  • Sheep Diseases / prevention & control
  • Vaccination / veterinary*
  • Vaccines / administration & dosage
  • Vaccines / genetics
  • Vaccines / immunology
  • Yeasts / genetics

Substances

  • Adjuvants, Immunologic
  • Antibodies, Helminth
  • Antigens, Helminth
  • Recombinant Proteins
  • Vaccines
  • Cathepsins
  • Cysteine Endopeptidases
  • cathepsin L5
  • endopeptidase B