Investigation of the combined efficacy of two Haemonchus contortus vaccines in weaner Merino sheep

Kebeta, M.M.; Hine, Brad C.; Walkden‐Brown, Stephen W.; Kahn, Lewis; Piedrafita, David; Bailey, S. R.; Doyle, Emma

doi:10.1016/j.vetpar.2021.109637

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Because these strains belong to same genus/species, after we analyzed the number of total coding genes in our study, we obtained a 776-bp mean of the transcript size from both Mexican H. contortus strains; this transcript size was similar to the one reported by Pavelich et al, 2019, who obtained 666-bp transcriptional size described for a H. contortus strain from New Zealand [ 29 ]. Early studies suggested the use of the H. contortus transcriptomic profile to identify significant gene sequences with potential use as targets for novel vaccination agents [ 15 , 19 , 28 ]. The transcriptome profile could also contribute to searching for an AR reduction strategy, based on the genetic mechanisms of adaption associated with anthelmintic drugs pressure and the host–parasite interaction [ 40 , 41 , 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…It can also contribute to our understanding of anthelmintic mechanisms and genes involved in nematode pathogenesis, among others [ 13 , 15 , 16 ]. Due to the importance of the genus Haemonchus , expanding our knowledge about the functional genes of this nematode is crucial for nematode control in grazing flocks and herds [ 16 , 18 , 19 ]. The objective of this study was therefore to assemble the transcriptome of H. contortus species as an important nematode model to contribute to the knowledge about the differential gene expression profile between two Mexican H. contortus strains under different AR statuses: one susceptible and the other resistant to ivermectin (IVMs and IVMr, respectively).…”

Section: Introductionmentioning

confidence: 99%

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Assembly and Analysis of Haemonchus contortus Transcriptome as a Tool for the Knowledge of Ivermectin Resistance Mechanisms

et al. 2023

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Haemonchus contortus (Hc) is an important parasitic nematode of small ruminants. In this study we assembled the transcriptome of Hc as a model to contribute to the knowledge about the profile of the differential gene expression between two Mexican Hc strains under different anthelmintic resistance statuses, one susceptible and the other resistant to ivermectin (IVMs and IVMr, respectively), in order to improve and/or to have new strategies of control and diagnosis. The transcript sequence reads were assembled and annotated. Overall, ~127 Mbp were assembled and distributed into 77,422 transcript sequences, and 4394 transcripts of the de novo transcriptome were matched base on at least one of the following criteria: (1) Phylum Nemathelminthes and Platyhelminthes, important for animal health care, and (2) ≥55% of sequence identity with other organisms. The gene ontology (GO) enrichment analysis (GOEA) was performed to study the level of gene regulation to IVMr and IVMs strains using Log Fold Change (LFC) filtering values ≥ 1 and ≥ 2. The upregulated-displayed genes obtained via GOEA were: 1993 (for LFC ≥ 1) and 1241 (for LFC ≥ 2) in IVMr and 1929 (for LFC ≥ 1) and 835 (for LFC ≥ 2) in IVMs. The enriched GO terms upregulated per category identified the intracellular structure, intracellular membrane-bounded organelle and integral component of the cell membrane as some principal cellular components. Meanwhile, efflux transmembrane transporter activity, ABC-type xenobiotic transporter activity and ATPase-coupled transmembrane transporter activity were associated with molecular function. Responses to nematicide activity, pharyngeal pumping and positive regulation of synaptic assembly were classified as biological processes that might be involved in events related to the anthelmintic resistance (AR) and nematode biology. The filtering analysis of both LFC values showed similar genes related to AR. This study deepens our knowledge about the mechanisms behind the processes of H. contortus in order to help in tool production and to facilitate the reduction of AR and promote the development of other control strategies, such as anthelmintic drug targets and vaccines.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assembly and Analysis of Haemonchus contortus Transcriptome as a Tool for the Knowledge of Ivermectin Resistance Mechanisms

et al. 2023

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“…Although the results provide identifications of immunogenic nematode parasite proteins, some false positives may be present due to non-specific binding and some false negatives or varying signal intensities may be present due to improper protein folding among the results or incorrect gene annotations on the draft nematode genomes used for recombinant protein production and for the bioinformatic prioritizations. In addition, it is difficult to correlate differences in antibody detection with outcomes in terms of infection clearance, since in some cases even with remarkably high antibody titers following vaccination, parasitic nematodes may persist and continue shedding eggs (as shown for both the Barbervax and Haemonchus-specific antibody vaccines in Haemonchus contortusinfected sheep (Kebeta et al, 2022)). However, Orthologous Protein Family clustering that includes comparisons with H. polygyrus bakeri predicted E/S proteins provides a context to evaluate the parasite protective capacity of identified proteins in laboratory mouse models of parasite infection.…”

Section: Discussionmentioning

confidence: 99%

Identification of broadly-conserved parasitic nematode proteins that activate immunity

Rosa,

Zarlenga,

Fournet

et al. 2023

Front. Parasitol.

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IntroductionSoil transmitted nematodes are impediments to human health and agricultural production. Poor anthelmintic efficiencies, the emergence of resistant strains, and the persistence of infective stages highlight the need for more effective control strategies. Parasitic nematodes elicit a Th2-type immune response that most often is not protective. Vaccination has thus far been unsuccessful due to unrealized antigenic characters and unknown mechanisms that nematodes use to circumvent host immunity.MethodsHere, we used a genomics/proteomics approach (including immunoblot experiments from pigs infected with T. suis) to prioritize putative immunogenic excretory/secretory (E/S) proteins conserved across and specific to several gastrointestinal (GI) parasitic nematode species. A cocktail of five recombinant proteins optimized for conserved GI nematode targets was used immunize pigs and test for active antibody responses in both the serum and intestinal ileal fluid of immunized pigs. An antibody-protein array of putative immunogenic proteins was developed from a combined bioinformatic, experimental, and literature-based prioritization of homologous parasite proteins.ResultsScreening the array with sera and ileal fluid samples from immunized pigs suggested cross-reactivity among homologous proteins and a general activation of immunity. PCA clustering showed that the overall immune responses were altered by immunization, but no substantial changes were observed following direct worm challenge with either Ascaris suum or Trichuris suis.DiscussionProteins that activated immunity are potential antigens for immunization and the multi-omics phylum-spanning prioritization database that was created is a valuable resource for identifying target proteins in a wide array of different parasitic nematodes. This research strongly supports future studies using a computational, comparative genomics/proteomics approach to produce an effective parasite vaccine.

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“…These features, together with evidence that third-stage larvae of H. contortus whose hrg-1 gene had been "knocked down" did not establish or survive within the permissive host animal, indicating that HRG-1 is indeed a promising intervention target. Given that HRG-1 is a membrane-bound protein expressed in the nematode's intestine, it could represent a novel vaccine target, since haem-binding glutathione transferases have been exploited in vaccine development against hookworm infection in humans [39][40][41], particularly if parenteral immunisation with recombinant Hc-HRG-1 or a sub-component thereof can stimulate protective immunity against H. contortus [42]. This aspect deserves exploration, with a focus on achieving longer lasting and more consistent immunoprotection in all age-groups and species of host animals (sheep and goats) than achievable using the commercially available vaccine (Barbervax) produced from native gutderived molecules from H. contortus [43][44][45][46][47].…”

Section: Plos Pathogensmentioning

confidence: 99%

Haem transporter HRG-1 is essential in the barber’s pole worm and an intervention target candidate

Yang

Zhou

et al. 2023

PLoS Pathog

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Parasitic roundworms (nematodes) have lost genes involved in the de novo biosynthesis of haem, but have evolved the capacity to acquire and utilise exogenous haem from host animals. However, very little is known about the processes or mechanisms underlying haem acquisition and utilisation in parasites. Here, we reveal that HRG-1 is a conserved and unique haem transporter in a broad range of parasitic nematodes of socioeconomic importance, which enables haem uptake via intestinal cells, facilitates cellular haem utilisation through the endo-lysosomal system, and exhibits a conspicuous distribution at the basal laminae covering the alimentary tract, muscles and gonads. The broader tissue expression pattern of HRG-1 in Haemonchus contortus (barber’s pole worm) compared with its orthologues in the free-living nematode Caenorhabditis elegans indicates critical involvement of this unique haem transporter in haem homeostasis in tissues and organs of the parasitic nematode. RNAi-mediated gene knockdown of hrg-1 resulted in sick and lethal phenotypes of infective larvae of H. contortus, which could only be rescued by supplementation of exogenous haem in the early developmental stage. Notably, the RNAi-treated infective larvae could not establish infection or survive in the mammalian host, suggesting an indispensable role of this haem transporter in the survival of this parasite. This study provides new insights into the haem biology of a parasitic nematode, demonstrates that haem acquisition by HRG-1 is essential for H. contortus survival and infection, and suggests that HRG-1 could be an intervention target candidate in a range of parasitic nematodes.

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Investigation of the combined efficacy of two Haemonchus contortus vaccines in weaner Merino sheep

Cited by 5 publications

References 27 publications

Assembly and Analysis of Haemonchus contortus Transcriptome as a Tool for the Knowledge of Ivermectin Resistance Mechanisms

Assembly and Analysis of Haemonchus contortus Transcriptome as a Tool for the Knowledge of Ivermectin Resistance Mechanisms

Identification of broadly-conserved parasitic nematode proteins that activate immunity

Haem transporter HRG-1 is essential in the barber’s pole worm and an intervention target candidate

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