In vitro attenuated Histomonas meleagridis does not revert to virulence, following serial in vivo passages in turkeys or chickens

Sulejmanovic, Tarik; Liebhart, Dieter; Heß, Michael

doi:10.1016/j.vaccine.2013.08.098

Cited by 19 publications

(10 citation statements)

References 23 publications

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“…Previously, the safety of the vaccine has been tested by administering 10 4 cultured histomonads exclusively via the oral route for turkeys and with an additional dose of 10 4 parasites cloacally to chickens. Challenges were tested in turkeys with 10 4 parasites administered by the cloaca route only ( 5 – 7 ). The birds in the main experiment of this study were inoculated with a 3 × 10 5 histomonads administrated both orally and cloacally which proved the tentative vaccine safe as noticed in vaccinated hosts together with the capability of inducing a potent immunity during challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Histomonads can then migrate to the liver leading to multifocal areas of inflammation and necrosis, which is commonly observed in infected turkeys ( 4 ). Recently, a live vaccine prepared from an in vitro passaged clonal culture of H. meleagridis has been experimentally shown as safe and capable of providing protection from the disease ( 5 – 7 ). However, investigations on the immune response against histomonosis are rare and relevant protective mechanisms are so far not identified.…”

Section: Introductionmentioning

confidence: 99%

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Allocation of Interferon Gamma mRNA Positive Cells in Caecum Hallmarks a Protective Trait Against Histomonosis

et al. 2018

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Histomonosis is a parasitic disease of gallinaceous birds characterized by necrotic lesions in cacum and liver that usually turns fatal in turkeys while it is less severe in chickens. Vaccination using in vitro attenuated Histomonas meleagridis has been experimentally shown to confer protection against histomonosis. The protective mechanisms that underpin the vaccine-induced immune response are not resolved so far. Therefore, the actual study aimed to evaluate the location and quantitative distribution patterns of signature cytokines of type 1 [interferon gamma (IFN-γ)] or type 2 [interleukin (IL)-13] immune responses in vaccinated or infected hosts. An intergroup and interspecies difference in the spatial and temporal distribution patterns of cytokine mRNA positive cells was evident. Quantification of cells showed a significantly decreased percentage of IFN-γ mRNA positive cells at 4 days post-inoculation (DPI) in caeca of turkeys inoculated exclusively with the attenuated or the virulent inocula, compared to control birds. The decrement was followed by a surge of cells expressing mRNA for IFN-γ or IL-13, reaching a peak of increment at 10 DPI. By contrast, turkeys challenged following vaccination showed a slight increment of cecal IFN-γ mRNA positive cells at 4 DPI after which positive cell counts became comparable to control birds. The increase in infected birds was accompanied by an extensive distribution of positively stained cells up to the muscularis layer of cecal tissue whereas the vaccine group maintained an intact mucosal structure. In chickens, the level of changes of positive cells was generally lower compared to turkeys. However, control chickens were found with a higher percentage of IFN-γ mRNA positive cells in cecum compared to their turkey counterparts indicating a higher resistance to histomonosis, similar to the observation in immunized turkeys. In chickens, it could be shown that the changes of cytokine-positive cells were related to variations of mononuclear cells quantified by immunofluorescence. Furthermore, gene expression measured by reverse transcription quantitative real time PCR confirmed variations in organs between the different groups of both bird species. Overall, it can be concluded that a proportionally increased, yet controlled, allocation of IFN-γ mRNA positive cells in caeca hallmarks a protective trait against histomonosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Allocation of Interferon Gamma mRNA Positive Cells in Caecum Hallmarks a Protective Trait Against Histomonosis

et al. 2018

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“…The establishment of a mono-eukaryotic H. meleagridis culture derived from a single cell and its successful stable attenuation after numerous in vitro passages opened the road for the development of innovative strategies against the flagellate (Hess et al, 2006 ; Sulejmanovic et al, 2013 ). Such attenuated parasites which are propagated in vitro in a mixed bacterial content, termed as xenic culture, were proven to be safe and effective as a vaccine (Liebhart et al, 2011 , 2013 ).…”

Section: Introductionmentioning

confidence: 99%

An Alliance of Gel-Based and Gel-Free Proteomic Techniques Displays Substantial Insight Into the Proteome of a Virulent and an Attenuated Histomonas meleagridis Strain

Monoyios

Hummel

Nöbauer

et al. 2018

Front. Cell. Infect. Microbiol.

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The unicellular protozoan Histomonas meleagridis is notorious for being the causative agent of histomonosis, which can cause high mortality in turkeys and substantial production losses in chickens. The complete absence of commercially available curative strategies against the disease renders the devising of novel approaches a necessity. A fundamental step toward this objective is to understand the flagellate's virulence and attenuation mechanisms. For this purpose we have previously conducted a comparative proteomic analysis of an in vitro cultivated virulent and attenuated histomonad parasite using two-dimensional electrophoresis and MALDI-TOF/TOF. The current work aimed to substantially extend the knowledge of the flagellate's proteome by applying 2D-DIGE and sequential window acquisition of all theoretical mass spectra (SWATH) MS as tools on the two well-defined strains. In the gel-based experiments, 49 identified protein spots were found to be differentially expressed, of which 37 belonged to the in vitro cultivated virulent strain and 12 to the attenuated one. The most frequently identified proteins in the virulent strain take part in cytoskeleton formation, carbohydrate metabolism and adaptation to stress. However, post-translationally modified or truncated ubiquitous cellular proteins such as actin and GAPDH were identified as upregulated in multiple gel positions. This indicated their contribution to processes not related to cytoskeleton and carbohydrate metabolism, such as fibronectin or plasminogen binding. Proteins involved in cell division and cytoskeleton organization were frequently observed in the attenuated strain. The findings of the gel-based studies were supplemented by the gel-free SWATH MS analysis, which identified and quantified 42 significantly differentially regulated proteins. In this case proteins with peptidase activity, metabolic proteins and actin-regulating proteins were the most frequent findings in the virulent strain, while proteins involved in hydrogenosomal carbohydrate metabolism dominated the results in the attenuated one.

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“…In continuation, successful oral administration of attenuated histomonads to day-old turkeys was demonstrated successfully for the first time (Liebhart et al, 2010). The established vaccine candidate was further investigated for its safety, with the outcome that (i) no clinical signs or pathological lesions were found in chickens and turkeys that were vaccinated and (ii) the strain used for vaccination did not revert to virulence following consecutive passages in both host species, and only minimal lesions were noted (Sulejmanovic et al, 2013). In another study, the vaccine was applied as a monoxenic inoculum which had no effect on the attenuation and efficacy (Ganas et al, 2012).…”

Section: Investigations On Vaccination Against Histomonosismentioning

confidence: 99%

Histomonosis in poultry: previous and current strategies for prevention and therapy

et al. 2016

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Histomonosis is a parasitic disease of poultry with worldwide prevalence. The disease can cause morbidity and mortality in chicken and turkey flocks entailing severe economic losses. In the first half of the last century, there was a high demand to control histomonosis as the turkey industry was severely affected by the disease. Consequently, numerous chemical compounds were tested for their efficacy against Histomonas meleagridis with varying outcomes, that are summarized and specified in this review. At the same time, preliminary attempts to protect birds with cultured histomonads indicated the possibility of vaccination. Several years ago antihistomonal drugs were banned in countries with tight regulations on pharmaceuticals in order to comply with the demand of consumer protection. As a consequence, outbreaks of histomonosis in poultry flocks increased and the disease became endemic again. New approaches to prevent and treat histomonosis are, therefore, needed and recently performed studies focused on various areas to combat the disease, from alternative chemotherapeutic substances to plant-derived compounds until vaccination, altogether reviewed here. Considering existing regulations and the overall outcome of experimental studies, it can be concluded that vaccination is very promising, despite the fact that various challenges need to be addressed until the first ever developed vaccine based upon live flagellates in human or bird medicine can be marketed.

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In vitro attenuated Histomonas meleagridis does not revert to virulence, following serial in vivo passages in turkeys or chickens

Cited by 19 publications

References 23 publications

Allocation of Interferon Gamma mRNA Positive Cells in Caecum Hallmarks a Protective Trait Against Histomonosis

Allocation of Interferon Gamma mRNA Positive Cells in Caecum Hallmarks a Protective Trait Against Histomonosis

An Alliance of Gel-Based and Gel-Free Proteomic Techniques Displays Substantial Insight Into the Proteome of a Virulent and an Attenuated Histomonas meleagridis Strain

Histomonosis in poultry: previous and current strategies for prevention and therapy

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