.
Farmers, veterinarians and other animal health managers in the livestock sector are currently missing sufficient information on prevalence and burden of contagious endemic animal diseases. They need adequate tools for risk assessment and prioritization of control measures for these diseases. The DECIDE project develops data-driven decision-support tools, which present (i) robust and early signals of disease emergence and options for diagnostic confirmation; and (ii) options for controlling the disease along with their implications in terms of disease spread, economic burden and animal welfare. DECIDE focuses on respiratory and gastro-intestinal syndromes in the three most important terrestrial livestock species (pigs, poultry, cattle) and on reduced growth and mortality in two of the most important aquaculture species (salmon and trout). For each of these, we (i) identify the stakeholder needs; (ii) determine the burden of disease and costs of control measures; (iii) develop data sharing frameworks based on federated data access and meta-information sharing; (iv) build multivariate and multi-level models for creating early warning systems; and (v) rank interventions based on multiple criteria. Together, all of this forms decision-support tools to be integrated in existing farm management systems wherever possible and to be evaluated in several pilot implementations in farms across Europe. The results of DECIDE lead to improved use of surveillance data and evidence-based decisions on disease control. Improved disease control is essential for a sustainable food chain in Europe with increased animal health and welfare and that protects human health.
Foot-and-mouth disease (FMD) is a highly contagious viral disease of livestock that has a significant economic impact on the country. The inactivated vaccine is the most widely used type of FMD vaccine, with the inactivation procedure being one of the most crucial steps. This study aims to evaluate the inactivation kinetics and post-vaccination immune responses of FMD vaccine developed using three inactivation methods: binary ethyleneimine (BEI), formaldehyde, and a combined approach. A randomized controlled trial included 20 healthy, unvaccinated calves, allocating five calves to each of the three vaccinated groups and one control (unvaccinated) group. A monovalent inactivated FMDV vaccine (O-ETH/38/2005) was developed using the above three inactivation methods. Each prepared vaccine was then randomly administered to seronegative experimental calves. Blood samples were collected at 0, 7, 14, 21, 28, and 42 days post-vaccination and analyzed using solid-phase competitive enzyme-linked immunosorbent assay to assess the antibody response level. Regression analysis demonstrated that both the combined and BEI-inactivated vaccines exhibited linear kinetics, with higher and comparable virus titer reduction rates of 1.27 and 1.05 log10 TCID50 per hour, respectively. The formaldehyde-inactivated vaccine exhibited curvilinear kinetics with a slower rate of 0.34 log10 TCID50 per hour. This demonstrated that methods for virus inactivation lead to significant variability in the antibody responses induced by the vaccine. Significantly higher antibody titer (p = 0.006) was found in a vaccine inactivated by combined methods compared to those inactivated using formaldehyde. Comparative analysis revealed no significant difference in antibody responses between combination-inactivated and BEI-inactivated vaccines (p = 0.696). This study revealed that the combined approach has faster inactivation and better immune induction. Thus, It is recommended to replace formalin with a combined inactivant following optimization and validation of strain-specific inactivation procedures to enhance FMD vaccine efficiency.
PURPOSE:Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new cancer treatment modality that employs radium-224-loaded metal sources implanted in solid tumors to disperse alpha-emitting atoms within a therapeutic "kill-zone" of a few millimeters around each source. Preclinical studies have demonstrated tumor growth delay in various cancer types, including glioblastoma multiforme, and the method is used in clinical trials for patients with skin and head and neck cancer. This study aims to assess the safety and feasibility of implementing Alpha DaRT for brain tumor treatment in a large animal model. METHODS:Alpha-DaRT sources were delivered via image-guided stereotactic implantation into both hemispheres of eight swine. 1-3 layers of radial deployment of 7 sources were delivered through a single penetration point into each hemisphere. A 90-day follow-up period included clinical evaluation, brain MRI, head CT, blood, CSF, urine, and feces sampling, and an analysis of source location over time. Brain tissue pathology was performed on termination. RESULTS:Alpha-DaRT sources were reproducibly and efficiently delivered to the brain cortex and subcortex. No unexpected abnormalities were detected in blood or CSF samples. MRI and CT scans revealed no evidence of major bleeding or infection. Measurements of 212Pb in blood and CSF exhibited the expected exponential decay from day 7 to day 14 post-source implantation. Minimal spatial and temporal movements of the sources were noted. Histopathological analysis demonstrated locally confined findings in brain parenchyma in a very close proximity to the sources. CONCLUSION:Alpha-DaRT sources can be safely delivered into a large animal brain using image-guided stereotactic implantation. These findings support further exploration of Alpha DaRT as a potential treatment modality for brain tumors.
The COVID-19 pandemic has resulted in millions of deaths and affected socioeconomic structure worldwide and the search for new antivirals and treatments are still ongoing. In the search for new drug targets and to increase our understanding of the disease, we applied large-scale immunofluorescence profiling to explore host cell response to SARS-CoV-2 infection. Among the 602 host proteins studied in this host response profiling, changes in abundance and subcellular localization were observed for 97 proteins, with 45 proteins showing increased abundance and 10 reduced abundance. 20 proteins displayed changed localization upon infection and an additional 22 proteins displayed altered abundance and localization, together contributing to diverse reshuffling of the host cell protein landscape during infection. We then selected existing and approved small-molecule drugs (n = 123) against our identified host response proteins and identified one compound - elesclomol, that significantly reduced antiviral activity. Our study introduces a novel, targeted and systematic approach based on host protein profiling, to identify new targets for drug repurposing. The dataset of > 100,000 immunofluorescence images from this study are published as a resource available for further studies. AUTHOR SUMMARY: In this study we have evaluated a new approach for identifying drugs that could be used as antiviral drugs, in this case demonstrated for SARS CoV-2. By mining the literature for reported interactions between SARS CoV-2 viral components and host cell proteins, we identified a few hundred host proteins suggested to interact with the virus upon infection. To explore these viral-host interaction proteins further, we developed an image based assay using immunofluorescence and confocal microscopy to visualize the host proteins within infected and non infected cells. This was possible due to the proteome wide collection of antibodies generated within the Human Protein Atlas project, with the aim to systematically map the human proteome in cells and across tissues. The host proteins that altered their location or abundance level upon infection were regarded as putative targets for drug repurposing and we subsequently tested 123 drugs that were targeting a subset of these host proteins. Applying these drugs on two different cell types infected with SARS-CoV-2, revealed a non toxic antiviral effect for one compound that can be explored further as a treatment regimen for SARS-CoV-2 infection. The approach is novel since it combines a targeted approach for drug repurposing screening, giving insight into mechanism of action from start. As such it has the potential to accelerate drug repurposing or identification of targets for new drugs.
