Efficacy of a multivalent vaccine against Fasciola hepatica infection in sheep

Zafra, R.; Buffoni, L.; Pérez–Caballero, Ramón; Molina-Hernández, Verónica; Ruiz-Campillo, María Teresa; Pérez, J.; Martı́nez-Moreno, A.; Moreno, Francisco J. Magraner

doi:10.1186/s13567-021-00895-0

Cited by 25 publications

(30 citation statements)

References 53 publications

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“…Over the last few decades, progress has been made in the isolation, characterisation and testing of a number of native and recombinant molecules as vaccines against liver fluke disease in ruminant hosts ( 33 ). However, data from vaccine trials have been inconsistent ( 14 ), and some recent trials with recombinant antigens failed to induce protection against fluke infection ( 20 ) or achieved only a minor reduction of fluke burdens ( 34 ). In spite of evidence that effective vaccination may be possible, design of smart vaccines will require more knowledge about the immune response to F. hepatica , which can be provided by big-data approaches such as transcriptomics.…”

Section: Discussionmentioning

confidence: 99%

Timing of Transcriptomic Peripheral Blood Mononuclear Cell Responses of Sheep to Fasciola hepatica Infection Differs From Those of Cattle, Reflecting Different Disease Phenotypes

et al. 2021

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Infection with the zoonotic trematode Fasciola hepatica, common in many regions with a temperate climate, leads to delayed growth and loss of productivity in cattle, while infection in sheep can have more severe effects, potentially leading to death. Previous transcriptomic analyses revealed upregulation of TGFB1, cell death and Toll-like receptor signalling, T-cell activation, and inhibition of nitric oxide production in macrophages in response to infection. However, the differences between ovine and bovine responses have not yet been explored. The objective of this study was to further investigate the transcriptomic response of ovine peripheral blood mononuclear cells (PBMC) to F. hepatica infection, and to elucidate the differences between ovine and bovine PBMC responses. Sixteen male Merino sheep were randomly assigned to infected or control groups (n = 8 per group) and orally infected with 120 F. hepatica metacercariae. Transcriptomic data was generated from PBMC at 0, 2 and 16 weeks post-infection (wpi), and analysed for differentially expressed (DE) genes between infected and control animals at each time point (analysis 1), and for each group relative to time 0 (analysis 2). Analysis 2 was then compared to a similar study performed previously on bovine PBMC. A total of 453 DE genes were found at 2 wpi, and 2 DE genes at 16 wpi (FDR < 0.1, analysis 1). Significantly overrepresented biological pathways at 2 wpi included role of PKR in interferon induction and anti-viral response, death receptor signalling and RIG-I-like receptor signalling, which suggested that an activation of innate response to intracellular nucleic acids and inhibition of cellular apoptosis were taking place. Comparison of analysis 2 with the previous bovine transcriptomic study revealed that anti-inflammatory response pathways which were significantly overrepresented in the acute phase in cattle, including IL-10 signalling, Th2 pathway, and Th1 and Th2 activation were upregulated only in the chronic phase in sheep. We propose that the earlier activation of anti-inflammatory responses in cattle, as compared with sheep, may be related to the general absence of acute clinical signs in cattle. These findings offer scope for “smart vaccination” strategies for this important livestock parasite.

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Section: Discussionmentioning

confidence: 99%

Timing of Transcriptomic Peripheral Blood Mononuclear Cell Responses of Sheep to Fasciola hepatica Infection Differs From Those of Cattle, Reflecting Different Disease Phenotypes

et al. 2021

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“…Over the last few decades, progress has been made in the isolation, characterisation and testing of a number of native and recombinant molecules as vaccines against liver fluke disease in ruminant hosts (Toet et al, 2014). However, data from vaccine trials have been inconsistent (Molina-Hernández et al, 2015), and some recent trials with recombinant antigens failed to induce protection against fluke infection (Fu et al, 2016) or achieved only a minor reduction of fluke burdens (Zafra et al, 2021). In spite of evidence that effective vaccination may be possible, design of smart vaccines will require more knowledge about the immune response to F. hepatica , which can be provided by big-data approaches such as transcriptomics.…”

Section: Discussionmentioning

confidence: 99%

Timing of transcriptomic peripheral blood mononuclear cell responses of sheep to Fasciola hepatica infection differs from those of cattle, reflecting different disease phenotypes

Niedziela

Naranjo‐Lucena

Molina-Hernández

et al. 2021

Preprint

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Infection with the zoonotic trematode Fasciola hepatica, common in many regions with a temperate climate, leads to delayed growth and loss of productivity in cattle, while infection in sheep can have more severe effects, potentially leading to death. Previous transcriptomic analyses revealed upregulation of TGFB1, cell death and Toll-like receptor signalling, T-cell activation, and inhibition of nitric oxide production in macrophages in response to infection. However, the differences between ovine and bovine responses have not yet been explored. The objective of this study was to further investigate the transcriptomic response of ovine peripheral blood mononuclear cells (PBMC) to F. hepatica infection, and to elucidate the differences between ovine and bovine PBMC responses. Sixteen male Merino sheep were randomly assigned to infected or control groups (n = 8 per group) and orally infected with 120 F. hepatica metacercariae. Transcriptomic data was generated from PBMC at 0, 2 and 16 weeks post-infection (wpi), and analysed for differentially expressed (DE) genes between infected and control animals at each time point (analysis 1), and for each group relative to time 0 (analysis 2). Analysis 2 was then compared to a similar study performed previously on bovine PBMC. A total of 453 DE genes were found at 2 wpi, and 2 DE genes at 16 wpi (FDR < 0.1, analysis 1). Significantly overrepresented biological pathways at 2 wpi included role of PKR in interferon induction and anti-viral response, death receptor signalling and RIG-I-like receptor signalling, which suggested that an activation of innate response to intracellular nucleic acids and inhibition of cellular apoptosis were taking place. Comparison of analysis 2 with the previous bovine transcriptomic study revealed that anti-inflammatory response pathways which were significantly overrepresented in the acute phase in cattle, including IL-10 signalling, Th2 pathway, and Th1 and Th2 activation were upregulated only in the chronic phase in sheep. We propose that the earlier activation of anti-inflammatory responses in cattle, as compared with sheep, may be related to the general absence of acute clinical signs in cattle. These findings offer scope for smart vaccination strategies for this important livestock parasite.

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“…Groups VAC1 (n = 10) and VAC2 (n = 10) were immunized subcutaneously with two doses, 4 weeks apart, of a multivalent vaccine. The formulation of the two vaccines assessed in this study were published previously by [11] finding a reduction of fluke burden (37.2%) and egg output (28.71%) in comparison to IC group. Briefly, each vaccine dose (2 mL) contained a cocktail of F. hepatica recombinant proteins including cathepsin L1 (rFhCL1), peroxiredoxin (rFhPrx), helminth defence molecules (rFhHDM), and leucine aminopeptidase (rFhLAP) at a concentration of 100 μg per antigen emulsified in two different adjuvants, Montanide ISA 61 VG (Seppic, Puteaux, France) and Alhydrogel ® adjuvant 2% (InvivoGen, San Diego, CA, USA), respectively.…”

Section: Experimental Designmentioning

confidence: 97%

“…Briefly, each vaccine dose (2 mL) contained a cocktail of F. hepatica recombinant proteins including cathepsin L1 (rFhCL1), peroxiredoxin (rFhPrx), helminth defence molecules (rFhHDM), and leucine aminopeptidase (rFhLAP) at a concentration of 100 μg per antigen emulsified in two different adjuvants, Montanide ISA 61 VG (Seppic, Puteaux, France) and Alhydrogel ® adjuvant 2% (InvivoGen, San Diego, CA, USA), respectively. The F. hepatica recombinant proteins were obtained as described [11]. Group IC (n = 10) was unimmunized and infected; and group UC (n = 7) was unimmunized and uninfected.…”

Section: Experimental Designmentioning

confidence: 99%

A Partially Protective Vaccine for Fasciola hepatica Induced Degeneration of Adult Flukes Associated to a Severe Granulomatous Reaction in Sheep

Molina-Hernández

Ruiz-Campillo

Martínez-Moreno

et al. 2021

Animals

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Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since current anthelmintic therapy is no longer sustainable. A better knowledge of the host-parasite interaction is needed for the design of effective vaccines. The present study evaluates the microscopical hepatic lesions in sheep immunized with a partially protective vaccine (VAC1), a non-protective vaccine (VAC2), and an infected control group (IC). The nature of granulomatous inflammation associated with degeneration of adult flukes found in the VAC1 group was characterized by immunohistochemistry. Hepatic lesions (fibrous perihepatitis, chronic tracts, bile duct hyperplasia, infiltration of eosinophils and lymphocytes and plasma cells) were significantly less severe in the VAC1 group than in the IC group. Dead adult flukes within bile ducts were observed only in the VAC1 group and were surrounded by a severe granulomatous inflammation composed by macrophages and multinucleate giant cells with a high expression of lysozyme, CD163 and S100 markers, and a low expression of CD68. Numerous CD3+ T lymphocytes and scarce infiltrate of FoxP3+ Treg and CD208+ dendritic cells were present. This is the first report describing degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a F. hepatica vaccine trial.

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Efficacy of a multivalent vaccine against Fasciola hepatica infection in sheep

Cited by 25 publications

References 53 publications

Timing of Transcriptomic Peripheral Blood Mononuclear Cell Responses of Sheep to Fasciola hepatica Infection Differs From Those of Cattle, Reflecting Different Disease Phenotypes

Timing of Transcriptomic Peripheral Blood Mononuclear Cell Responses of Sheep to Fasciola hepatica Infection Differs From Those of Cattle, Reflecting Different Disease Phenotypes

Timing of transcriptomic peripheral blood mononuclear cell responses of sheep to Fasciola hepatica infection differs from those of cattle, reflecting different disease phenotypes

A Partially Protective Vaccine for Fasciola hepatica Induced Degeneration of Adult Flukes Associated to a Severe Granulomatous Reaction in Sheep

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