A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production

Silvane, Leonardo; Celias, Daiana Pamela; Romagnoli, Pablo A.; Maletto, Belkys A.; Vallecillo, María F. Sánchez; Chiapello, Laura S.; Palma, Santiago Daniel; Allemandi, Daniel Alberto; Sanabria, Rodrigo Eduardo Fabrizio; Pruzzo, Cesar; Motrán, Claudia Cristina; Cervi, Laura

doi:10.3389/fimmu.2020.02087

Cited by 15 publications

(8 citation statements)

References 64 publications

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“…Kunitz inhibitors have been recognized as promising vaccine targets, as they play a crucial role in modulating host immunity 77 – 79 . It is worth noting that Kunitz inhibitors have already shown promise as vaccine candidates in other helminths, such as Fasciola hepatica and Schistosoma mansoni 78 , 80 – 83 . Notably, Kunitz protease inhibitor gene Smp_147730 in S. mansoni is 146 amino-acid long and contains only one Kunitz/bovine protease inhibitor domain 81 similar to VDM15541.…”

Section: Resultsmentioning

confidence: 99%

Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti

Aarthy,

Pandiyan,

Paramasivan

et al. 2024

Sci Rep

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This study employed subtractive proteomics and immunoinformatics to analyze the Wuchereria bancrofti proteome and identify potential therapeutic targets, with a focus on designing a vaccine against the parasite species. A comprehensive bioinformatics analysis of the parasite's proteome identified 51 probable therapeutic targets, among which "Kunitz/bovine pancreatic trypsin inhibitor domain-containing protein" was identified as the most promising vaccine candidate. The candidate protein was used to design a multi-epitope vaccine, incorporating B-cell and T-cell epitopes identified through various tools. The vaccine construct underwent extensive analysis of its antigenic, physical, and chemical features, including the determination of secondary and tertiary structures. Docking and molecular dynamics simulations were performed with HLA alleles, Toll-like receptor 4 (TLR4), and TLR3 to assess its potential to elicit the human immune response. Immune simulation analysis confirmed the predicted vaccine’s strong binding affinity with immunoglobulins, indicating its potential efficacy in generating an immune response. However, experimental validation and testing of this multi-epitope vaccine construct would be needed to assess its potential against W. bancrofti and even for a broader range of lymphatic filarial infections given the similarities between W. bancrofti and Brugia.

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Section: Resultsmentioning

confidence: 99%

Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti

Aarthy,

Pandiyan,

Paramasivan

et al. 2024

Sci Rep

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“…The increase of gene expression for INF-ɣ in the liver of the IC and V2 groups as compared to the UC groups agrees with the increase of this cytokine in the liver of buffaloes chronically infected with F. gigantica [ 26 ] and the liver of F. hepatica infected sheep during early stages of infection [ 20 , 22 ], but it contrasts with the lack of significant gene expression increase in the liver of chronically F. hepatica infected sheep [ 22 ] and with the significant decrease of IFN-ɣ expression in the liver of cattle with chronic natural fasciolosis [ 27 ]. Splenocytes from mice protected with a Kunitz vaccine also showed increased IFN-ɣ expression [ 28 ]. The increased INF-ɣ liver expression during early stages of F. hepatica infection in sheep has been attributed to a response to hepatic injuries caused by the parasite such as necrosis and granuloma formation [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Th1/Th2, regulatory cytokines and transcriptional factor FoxP3 in sheep immunized with a partially protective and non-protective vaccine and challenged with Fasciola hepatica

Ruiz-Campillo,

Pacheco,

Abril

et al. 2024

Vet Res

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Gene expression for Th1/Th2 cytokines (IL-4 and IFN-ɣ), regulatory cytokines (TGF-β and IL-10) and the transcriptional factor FoxP3 was analyzed in the liver and hepatic lymph nodes (HLN) from sheep immunized with partially protective and non-protective vaccine candidates and challenged with Fasciola hepatica. FoxP3 T cells were also evaluated by immunohistochemistry (IHQ). The most remarkable difference between the partially protected vaccinated (V1) group and the non-protected vaccinated (V2) group was a more severe expansion of FoxP3 T cells recorded by IHQ in both the liver and HLN of the V2 group as compared to the V1 group, whereas no differences were found between the V2 group and the infected control (IC) group. Similar results were recorded for FoxP3 gene expression although significant differences among V1 and V2 groups were only significant in the HLN, while FoxP3 gene expression was very similar in the V2 and IC groups both in the liver and HLN. No significant differences for the remaining cytokines were recorded between the V1 and V2 groups, but in the liver the V2 group shows significant increases of IFN-ɣ and IL-10 as compared to the uninfected control (UC) group whereas the V1 group did not. The lower expansion of FoxP3 T cells and lower increase of IFN-ɣ and IL-10 in the partially protected vaccinated group may be related with lower hepatic lesions and fluke burdens recorded in this group as compared to the other two infected groups. The most relevant change in regulatory cytokine gene expression was the significant increase of TGF-β in the liver of IC, V1 and V2 groups as compared to the UC group, which could be related to hepatic lesions.

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“…Apart from this unique property, these proteins were copiously secreted by the parasite early and throughout its evolution in the host [ 11 ]. Their ability to induce antibodies has also been demonstrated in mice immunized with sFhKT [ 29 ] and sheep. However, these proteins have not yet been evaluated in the diagnostic tests for fasciolosis.…”

Section: Discussionmentioning

confidence: 99%

Antibody detection against Kunitz-type protein in Fasciola hepatica experimentally infected sheep using enzyme-linked immunosorbent assay (ELISA)

Ahumada,

Godino,

Guasconi

et al. 2023

International Journal of Veterinary Science and Medicine

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Fasciolosis is a parasitic disease considered as emerging and neglected by the WHO. Sheep are highly susceptible to this disease, and affected flocks experience decreased productivity due to increased mortality, and the reduced quality of their products, such as wool and meat. To effectively control this disease, reliable and early diagnosis is essential for making decisions regarding antiparasitic application and/or the removal of affected animals. Currently, the diagnosis of F. hepatica in sheep relies on the detection of parasite eggs in faeces, a method that becomes reliable from week 10 post-infection. Consequently, there is a need for earlier diagnostic tools based on immune response. However, obtaining antigens for antibody detection has proven to be difficult and expensive. The aim of this study was to evaluate members of the Kunitz protein family of F. hepatica expressed in the form of a fusion protein in the serological diagnosis of F. hepatica in sheep. The performance of three recombinant F. hepatica Kunitz-type inhibitors (FhKT1.1, FhKT1.3, and FhKT4) was compared with a synthetic Kunitz-type peptide (sFhKT) in sera from sheep experimentally infected with F. hepatica , using an ELISA. Of these, FhKT1.1 showed the most promising diagnostic indicators, exhibiting high precision and low cross-reactivity, and thus potential for standardized production. The results of our study demonstrated that the application of FhKT1.1 is a valuable tool for early-stage diagnosis of F. hepatica in sheep. Such an early diagnosis can aid in implementing timely interventions and effectively managing the disease in sheep populations.

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A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production

Cited by 15 publications

References 64 publications

Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti

Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti

Evaluation of Th1/Th2, regulatory cytokines and transcriptional factor FoxP3 in sheep immunized with a partially protective and non-protective vaccine and challenged with Fasciola hepatica

Antibody detection against Kunitz-type protein in Fasciola hepatica experimentally infected sheep using enzyme-linked immunosorbent assay (ELISA)

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