Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica

Abstract

Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund’s adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide™ ISA720. Animals received three injections containing 20μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0–62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells.

Efficacy of a multivalent vaccine against Fasciola hepatica infection in sheep

“…The significant protection observed in group 1 (Montanide ISA 61 VG), agrees with previous studies performed in mice and cattle where Montanide was used as adjuvant mixed with FhSAP2 in mice [ 46 ] and with rFhCL1 in cattle [ 39 ]. This protection could not be observed when aluminium adjuvant (Alhydrogel) was used.…”

Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis

“…Saposins are known to be immunogenic in S. mansoni infection ( 38 ) and are candidate serodiagnostic antigens in S. japonicum infection ( 39 ). Recombinant saposins from the liver flukes Fasciola hepatica and Fasciola gigantica confer protection against challenge infection in animal models ( 40 , 41 ). Saposins from the gastrodermis of S. mansoni were tested as subunit vaccines in the mouse model and did not confer protection ( 38 ), but based on these findings herein, the S. haematobium proteins should be tested before final down-selection.…”

Targeting peptide‐enhanced antibody and CD11c+dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice

“…For instance, muramyl dipeptide and tuftsin targeting favors the induction of IFN-g by CD4 + through cellular immunity (27). Fasciola hepatica saposin-like protein-2 has potential as a vaccine against F. hepatica and the protection elicited by this molecule could be linked to a mechanism driven by the CD41 T h cells (57). The T h 17 cells are important for mucosal host defense and secreting signature cytokines, such as IL-17, which induce neutrophil recruitment and antimicrobial peptide production (58).…”