Phage display-based vaccine with cathepsin L and excretory-secretory products mimotopes of Fasciola hepatica induces protective cellular and humoral immune responses in sheep

• Published in: Veterinary parasitology Vol. 289; p. 109340
• Main Authors: Villa-Mancera, Abel, Olivares-Pérez, Jaime, Olmedo-Juárez, Agustín, Reynoso-Palomar, Alejandro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2021
• Subjects: Cathepsin L mimotopes; Cytokines; Excretory/secretory products; Fasciola hepatica; Phage display; Quil A; Sheep; Th1/Th2 paradigm; Vaccine; Cathepsin L mimotopes; Fasciola hepatica; Phage display; Quil A; Cytokines; Th1/Th2 paradigm; Sheep; Vaccine; Excretory/secretory products
• ISSN: 0304-4017; 1873-2550
• DOI: 10.1016/j.vetpar.2020.109340

•Immunodominant E/S products mimotopes were selected of phage display library.•Vaccinated sheep had 35.43–67.17 % lower worm burden post infection compared to controls.•Sheep immunised with phage-displayed mimotopes induced mixed Th1/Th2 immune response.•The epitope SGTFLFS from cathepsin L1 is highly immunogenic in parasite-infected sheep.•The vaccine has the advantages of high safety profile and inexpensive production.
Fasciolosis is a foodborne zoonotic disease that affects grazing animals and causes substantial economic losses worldwide. Excretory/secretory (E/S) products and cathepsin L mimotopes from Fasciola hepatica were used to immunise experimentally infected sheep against liver flukes. The level of protection was measured in terms of fluke burden, morphometric measurements and faecal egg counts, as well as the humoral and cellular immune responses elicited. Five groups of 5 sheep each were immunised with 1 × 1013 phage particles of cathepsin L1 (group 1: SGTFLFS), cathepsin L1 (group 2: WHVPRTWWVLPP) and immunodominant E/S product (group 3) mimotopes with Quil A adjuvant, and wild-type M13KE phage (group 4) at the beginning and as a booster two weeks later. The control group received phosphate-buff ;ered saline. All groups were challenged with 300 metacercariae at week four and slaughtered 18 weeks later. The mean fluke burdens after challenge were reduced by 52.39 % and 67.17 % in sheep vaccinated with E/S products (group 3) and cathepsin L1 (group 1: SGTFLFS), respectively; no eff ;ect was observed in animals inoculated with cathepsin L1 (group 2: WHVPRTWWVLPP). Animals vaccinated showed a significant reduction in fluke length and width, wet weights and egg output Sheep immunised with phage-displayed mimotopes induced the development of specific IgG1 and IgG2, indicating a mixed Th1/Th2 immune response. Measurement of cytokine levels revealed higher levels of IFN-γ as well as lower production of IL-4 in sheep vaccinated with the mimotope peptide of F. hepatica. Fluke-specific production of IFN-γ in immunised animals was significantly correlated with fluke burden (P < 0.01). As helminth infection progressed, increased levels of IL-4 were evident in the wild-type M13KE phage (group 4) and the control groups (group 5), accompanied by a downregulation of IFN-γ production. Vaccinated animals with cathepsin L1 (group 1: SGTFLFS) showed that amino acids located in the middle (64SG65) of the linear sequence and C-terminal end (314TFLFS318) were associated with significant protection.