Biology subjects

Wittek, T.

Publications and source records attributed to Wittek, T..

4 recordsLinked to original sources

bioRxiv2025

Safety and Efficacy of a Novel Glycoengineered Recombinant Vaccine Candidate against Haemonchus contortus in Sheep

Haemonchus contortus is considered the most pathogenic nematode in small ruminants and South American camelids, causing significant production losses and threatening animal welfare worldwide. Compared to the use of anthelmintic drugs, to which resistance is increasing, vaccination is considered a more sustainable control strategy. The safety and efficacy of a novel glycoengineered vaccine produced in Hi5 insect cells was evaluated in a randomized, controlled vaccination-and-challenge trial. For this, 35 male Jura x Lacaune sheep were assigned to five groups (n=7). Three experimental groups were vaccinated three times subcutaneously with 1 ml of either the commercial Barbervax(R) vaccine, the novel glycoengineered vaccine, consisting of a cocktail of five antigens (H11, H11-1, H11-2, H11-4 and GA1), or its non-glycoengineered counterpart before challenge with 5,000 H. contortus third-stage larvae. Clinical assessments, differential blood counts, serum antibody responses and fecal egg counts were evaluated at least once per week within the 16-week trial period. The abomasal worm burden was counted 40 days after challenge. The results of the mixed model showed a lower degree of anemia (mean packed cell volume (PCV) of 26.77%; mean hemoglobin (Hb) of 9.03 g/dl), in sheep vaccinated with the glycoengineered antigen cocktail compared to the unvaccinated group (PCV of 24.34%; mean Hb of 7.84 g/dl) and to the sheep vaccinated with the non-glycoengineered antigens (PCV of 26.11%; mean Hb of 8.53 g/dl). However, the degree of anemia was lower in sheep vaccinated with native antigens (Barbervax(R)) (PCV of 29.10%; mean Hb of 9.84 g/dl). Serum IgG and IgE antibodies were elevated in all vaccinated groups. Sheep vaccinated with the glycoengineered antigens showed a reduction in abomasal worm burden of 25.36% and a reduction of fecal egg shedding of 81.09%, the group vaccinated with non-glycoengineered antigen showed no worm reduction and a fecal egg count reduction of 32.72%. While there was no significant difference in egg shedding between sheep vaccinated with the glycoengineered antigens and sheep vaccinated with Barbervax(R) (98.32%; p = 0.33), the Barbervax(R) group showed a greater reduction in worm burden (86.40%). The results emphasize that glycoengineering of vaccine candidates is essential to achieve protective immunity against H. contortus in sheep and that the novel glycoengineered vaccine produced in insect cells clearly has the potential to reduce fecal egg shedding and worm burden, paving the way for the development of highly effective recombinant vaccines against this and other parasitic worms in the future.

molecular biology↗

bioRxiv2025

Glycoengineering of nematode antigens using insect cells: a promising approach for producing bioactive vaccine antigens of the barber's pole worm Haemonchus contortus

The H11 antigens, located on the intestinal microvilli of Haemonchus contortus, comprise a group of homologous aminopeptidases essential for the parasites digestion of blood meals. Native H11 proteins are promising vaccine antigens, capable of eliciting robust protective immunity against H. contortus in sheep and goats. However, recombinant forms of H11, produced either in conventional expression systems or in transgenic Caenorhabditis elegans, failed to replicate the protective efficacy of the native form, most likely due to two critical factors: improper glycosylation and protein misfolding. To address these limitations, we developed a novel strategy to produce recombinant Haemonchus antigens in glycoengineered insect cells. By introducing three C. elegans genes that alter the native N-glycosylation pathways of Hi5 insect cells we successfully expressed soluble H11 and GA1 antigens featuring nematode-specific glycan epitopes, including tri-fucosylated structures and the Gal{beta}1,4Fuc motif. The glycoengineered H11 proteins retained aminopeptidase activity and stimulated cytokine secretion from ovine peripheral blood mononuclear cells in vitro. These findings establish a platform for producing bioactive vaccine antigens against the parasitic nematode H. contortus.

bioengineering↗

bioRxiv2023

A systematic review on leptospirosis in cattle: a European perspective

BackgroundLeptospirosis is a zoonotic disease which is globally distributed. Bovine leptospirosis often results in economic losses through its severe impact on reproduction performance. However, a clear overview of the disease characteristics in European cattle is lacking. The objective of this review was to summarise the current knowledge and state of the research on the epidemiology of bovine leptospirosis in Europe. MethodologyWe conducted a systematic literature review following the PRISMA guidelines. We screened four electronic databases (Pubmed, Web of Science, Scopus, CABI) and included studies published between 2001 and 2021, in English, German, and French. Identified papers were filtered according to predefined inclusion and exclusion criteria. ResultsSixty-two studies were included. Reported seroprevalences were remarkably variable among studies, probably reflecting local variations but also heterogeneity in the study designs, laboratory methods, and sample sizes. The five most reported circulating serogroups in European cattle were Sejroe, Australis, Grippotyphosa, Icterohaemorrhagiae, and Pomona. Abortion and fertility disorders were the most frequently reported signs of leptospirosis in European cattle and were generally associated with chronic infections. The acute form primarily affected juveniles and foetuses. Risk factors positively associated with leptospirosis in cattle were diverse, related to environmental (e.g. geographic location), climatic (e.g. flooding), and medical (e.g. presence of other diseases) parameters, as well as farming practices (e.g. purchase policy, herd size) and individual factors (e.g. animal age and breed). ConclusionsClinical features of bovine leptospirosis in Europe cover a large range of signs and confirmation of infection requires laboratory tests. The epidemiology of the disease is very local, most probably influenced by context-specific factors. This work highlights several research gaps, including a lack of research data from several countries, a lack of methodological harmonisation, a lack of large-scale studies, an underrepresentation of beef herds in the studies, and a lack of molecular investigations. Author SummaryLeptospirosis is a zoonotic disease that has been reported in cattle worldwide. This review systematically evaluated the available literature (2001-2021) on (i) the methods of diagnostics, (ii) (sero)prevalence, (iii) circulating serogroups/serovars, (iv) clinical signs, (v) and risk factors associated with leptospirosis in European cattle. We found that the prevalence of the disease was very variable among studies. Similarly, a wide range of clinical signs were described, but the most frequently reported ones were abortion and fertility disorders. Risk factors of infection in cattle included herd size, purchase of animals, access to pasture and natural water sources, contact with other animal species, presence of other diseases on farm, animal age, and occurrence of extreme weather events. This review highlights that leptospirosis should be considered as a differential diagnosis in case of abortion or reproductive failure in European cattle and emphasises the need for integrated disease prevention and control measures at farm or regional level. We identified several research gaps, particularly a lack of research data from several countries, a lack of large-scale studies, an underrepresentation of beef herds, and a limited use of molecular tools in the studies.

microbiology↗

bioRxiv2021

Integrating diverse data sources to predict disease risk in dairy cattle

Livestock farming is currently undergoing a digital revolution and becoming increasingly data-driven. Yet, such data often reside in disconnected silos making it impossible to leverage their full potential to improve animal well-being. Here, we introduce a precision medicine approach, bringing together information streams from a variety of life domains of dairy cattle to predict eight common and economically important diseases. Dairy cows are part of a highly industrialised environment. The animals and their surroundings are closely monitored and environmental, behavioural and physiological observations are readily accessible yet seldomly integrated. We use random forest classifiers trained on data from 5,828 animals in 166 herds in Austria to predict occurrences of lameness, acute and chronic mastitis, anoestrus, ovarian cysts, metritis, ketosis (hyperketonemia) and periparturient hypocalcemia (milk fever). To assess the importance of specific cattle life domains and individual features for these predictions, we use multivariate logistic regression and feature permutation approaches. We show that disease in dairy cattle is a product of the complex interplay between a multitude of life domains such as housing, nutrition or climate, and identify a range of features that were previously not associated with increased disease risk. For example, we can predict anoestrus with high sensitivity and specificity (F1=0.72) and find that housing, feed and husbandry variables such as barn design and time on pasture are most predictive of this disease. We also find previously unknown associations of features with disease risk, for example humid conditions, which significantly decrease the odds for ketosis. Our findings pave the way towards data-driven point-of-care interventions and demonstrate the added value of integrating all available data in the dairy industry to improve animal well-being and reduce disease risk.

bioinformatics↗