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Vaccine Sep 2023Marek's disease (MD) is a highly contagious viral neoplastic disease of chickens caused by Marek's disease virus (MDV), resulting in significant economic losses to the...
Marek's disease (MD) is a highly contagious viral neoplastic disease of chickens caused by Marek's disease virus (MDV), resulting in significant economic losses to the poultry industry worldwide. The commonly used live and/or vectored MDV vaccines are expensive to produce and difficult to handle due to the requirement of liquid nitrogen for manufacturing and delivering frozen infected cells that are viable. In this study, we aimed to develop a Newcastle disease virus (NDV) vectored MDV vaccine that can be lyophilized, stored, and transported at 4 °C. Four NDV LaSota (LS) vaccine strain-based recombinant viruses expressing MDV glycoproteins gB, gC, gE, or gI were generated using reverse genetics technology. The biological assessments showed that these recombinant viruses were slightly attenuated in vivo yet retained similar growth kinetics and virus titers in vitro compared to the parental LaSota virus. Vaccination of leghorn chickens (Lines 15Ix7 F1 cross) with these recombinant viruses via intranasal and intraocular routes conferred different levels of protection against virulent MDV challenge. The recombinant expressing the MDV gB protein, rLS/MDV-gB, protected vaccinated birds significantly against MDV-induced tumor formation when challenged at 14 days post-vaccination (DPV) but moderately at 5 DPV. Whereas the other three recombinants provided little protection against the MDV challenge. All four recombinants conferred complete protection against the velogenic NDV challenge. These results demonstrated that the rLS/MDV-gB virus is a safe and efficacious dual vaccine candidate that can be lyophilized and potentially mass-administered via aerosol or drinking water to large chicken populations at a meager cost.
Topics: Animals; Chickens; Newcastle disease virus; Marek Disease; Herpesvirus 2, Gallid; Commerce
PubMed: 37598026
DOI: 10.1016/j.vaccine.2023.08.038 -
BMC Veterinary Research Oct 2023Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head...
BACKGROUND
Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head shaking. Approximately 2.1% of chickens died or were culled due to severe symptoms. Five carcasses were submitted to the Avian Disease Division of the Animal and Plant Quarantine Agency (APQA) for disease diagnosis.
RESULTS
Broilers displayed severe pericarditis and perihepatitis associated with gross lesions. Broilers also displayed microscopic lesions in the cerebrum and in the granular layer of the cerebellum, which were associated with multifocal perivascular cuffing and purulent necrosis in the cerebrum, and severe meningitis with heterophil and lymphocyte infiltration. Staphylococcus spp. were identified in the liver and heart using bacteriological culture. PCR/RT-PCR assays revealed that broilers were negative for avian Clostridium botulinum, Newcastle disease virus, and avian encephalomyelitis virus. Bacterial and viral metagenomic analysis of brain sample further revealed the presence of Pseudomonas spp. and Marek's disease virus, which are known etiological agents of chicken meningoencephalitis.
CONCLUSIONS
This study reports a diagnostic analysis of gross and histopathological lesions from 32-day-old broilers displaying unique neurological symptoms that revealed the presence of the several neurological diseases including meningoencephalitis. The causative agents associated with meningoencephalitis of broilers that had not been identified by routine diagnostic methods could be diagnosed by metagenomics, which proves the usefulness of metagenomics as a diagnostic tool for unknown neurological diseases in broilers.
Topics: Animals; Chickens; Newcastle disease virus; Newcastle Disease; Brain; Meningoencephalitis; Poultry Diseases
PubMed: 37798783
DOI: 10.1186/s12917-023-03732-y -
Molecular Therapy Oncolytics Sep 2023Unraveling the complexities of the tumor microenvironment (TME) and its correlation with responsiveness to immunotherapy has become a main focus in overcoming resistance...
Unraveling the complexities of the tumor microenvironment (TME) and its correlation with responsiveness to immunotherapy has become a main focus in overcoming resistance to such treatments. Targeting tumor-intrinsic retinoic acid-inducible gene-I (RIG-I), a sensor for viral RNA, was shown to transform the TME from an immunogenically "cold" state to an inflamed, "hot" lesion, which we demonstrated previously to be a crucial mediator of the efficacy of immune checkpoint inhibition with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). In this study, we focus on the chimeric oncolytic virus vesicular stomatitis virus (VSV)-Newcastle disease virus (NDV), comprised of genetic components of VSV and NDV, and we investigate its utility to support tumor-intrinsic RIG-I-dependent therapy with anti-CTLA-4. Overall, we demonstrate that treatment with VSV-NDV efficiently delays tumor growth and significantly prolongs survival in a murine model of malignant melanoma, which was further enhanced in combination with anti-CTLA-4. Although the direct oncolytic and pro-inflammatory effects of VSV-NDV therapy were independent of RIG-I activation, the synergism with anti-CTLA-4 therapy and associated activation of tumor-specific T cells was critically dependent on active RIG-I signaling in tumor cells. This work highlights the therapeutic value of utilizing an immune-stimulatory oncolytic virus to sensitize tumors to immune checkpoint inhibition.
PubMed: 37654972
DOI: 10.1016/j.omto.2023.08.001 -
Annals of Agricultural and... Sep 2023Intensive poultry farming is usually associated with massive exposure to organic dust, which is largely composed of microbiological origin particulates. The aim of the...
INTRODUCTION AND OBJECTIVE
Intensive poultry farming is usually associated with massive exposure to organic dust, which is largely composed of microbiological origin particulates. The aim of the study is to assess occupational and environmental exposures to airborne bacteria, fungi, and Marek's disease virus emitted by a poultry house.
MATERIAL AND METHODS
The concentrations of airborne microorganisms in a poultry house and its vicinity (250-500 m) at 3 different stages of the production cycle (i.e. empty poultry house, with 7-day-old and 42-day-old chickens) were stationary measured using Andersen and MAS impactors, as well as Coriolis and BioSampler impingers. The collected microbiota was taxonomically identified using molecular and biochemical techniques to characterize occupational exposure and its spatial dissemination.
RESULTS
Although Marek's disease virus was not present in the tested air samples, the appearance of reared chickens in the poultry house resulted in an increase in airborne bacterial and fungal concentrations up to levels of 1.26 × 10 CFU/m and 3.77 × 10 CFU/m, respectively. These pollutants spread around through the ventilation system, but their concentrations significantly decreased at a distance of 500 m from the chicken coop. A part of the identified microbiota was pathogens that were successfully isolated from the air by all 4 tested samplers.
CONCLUSIONS
The poultry house employees were exposed to high concentrations of airborne microorganisms, including pathogens that may lead to adverse health outcomes. To protect them, highly efficient hygienic and technical measures regarding the poultry house interior and its ventilation, respectively, should be introduced to prevent both unwanted pollution and subsequent emission of microbial contaminants during intensive chicken breeding.
PubMed: 37772519
DOI: 10.26444/aaem/172770 -
Science (New York, N.Y.) Dec 2023Microbial genomes from ancient chickens uncover the drivers of pathogenicity.
Microbial genomes from ancient chickens uncover the drivers of pathogenicity.
Topics: Animals; Chickens; Virulence; Marek Disease; Mardivirus; Genome, Viral
PubMed: 38096277
DOI: 10.1126/science.adl6094 -
Journal of Clinical Oncology : Official... Dec 2023There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across...
Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group.
PURPOSE
There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel.
METHODS
Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually).
RESULTS
The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text.
CONCLUSION
These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.
Topics: Humans; Clinical Trials as Topic; Urinary Bladder Neoplasms; Adjuvants, Immunologic; Carcinoma, Transitional Cell; Immunotherapy
PubMed: 37793077
DOI: 10.1200/JCO.23.00307 -
Avian Diseases Jan 2024The poultry industry is the largest source of meat and eggs for the growing human population worldwide. Key concerns in poultry farming are nutrition, management, flock... (Review)
Review
The poultry industry is the largest source of meat and eggs for the growing human population worldwide. Key concerns in poultry farming are nutrition, management, flock health, and biosecurity measures. As part of the flock health, use of live viral vaccines plays a vital role in the prevention of economically important and common viral diseases. This includes diseases and production losses caused by Newcastle disease virus, infectious bronchitis virus, infectious laryngotracheitis virus, infectious bursal disease virus, Marek's disease virus, chicken infectious anemia virus, avian encephalomyelitis virus, fowlpox virus, and avian metapneumovirus. These viruses cause direct and indirect harms, such as financial losses worth millions of dollars, loss of protein sources, and threats to animal welfare. Flock losses vary by type of poultry, age of affected animals, co-infections, immune status, and environmental factors. Losses in broiler birds can consist of high mortality, poor body weight gain, high feed conversion ratio, and increased carcass condemnation. In commercial layers and breeder flocks, losses include higher than normal mortality rate, poor flock uniformity, drops in egg production and quality, poor hatchability, and poor day-old-chick quality. Despite the emergence of technology-based vaccines, such as inactivated, subunit, vector-based, DNA or RNA, and others, the attenuated live vaccines remain as important as before. Live vaccines are preferred in the global veterinary vaccine market, accounting for 24.3% of the global market share in 2022. The remaining 75% includes inactivated, DNA, subunit, conjugate, recombinant, and toxoid vaccines. The main reason for this is that live vaccines can induce innate, mucosal, cellular, and humoral immunities by single or multiple applications. Some live vaccine combinations provide higher and broader protection against several diseases or strains of viruses. This review aimed to explore insights on the pros and cons of attenuated live vaccines commonly used against major viral infections of the global chicken industry, and the future road map for improvement.
Topics: Humans; Animals; Chickens; Viral Vaccines; Poultry Diseases; Vaccines, Attenuated; DNA
PubMed: 38300660
DOI: 10.1637/aviandiseases-D-23-99998 -
Frontiers in Aging Neuroscience 2023To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing...
INTRODUCTION
To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing PD. This is often difficult because most of the clinical markers are non-specific, common in PD but also common in older adults (e.g., sleep problems).
OBJECTIVE
We aimed to identify the clinical markers at high specificity for developing PD by comparing individuals with PD or prodromal PD to healthy controls.
METHODS
We investigated motor and non-motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 1 and 2 items) in 64 prodromal PD and 422 PD individuals calculating the odds ratios, adjusting for age and gender, for PD and prodromal PD versus 195 healthy controls. Symptoms at high specificity were defined as having an adjusted odds ratio ≥ 6.
RESULTS
Constipation had an adjusted odds ratio, 6.14 [95% CI: 2.94-12.80] showing high specificity for prodromal PD, and speech difficulties had an adjusted odds ratio, 9.61 [95% CI: 7.88-48.81] showing high specificity for PD. The proportion of participants showing these specific markers was moderate (e.g., prevalence of constipation was 43.75% in prodromal PD, and speech difficulties was 33.89% in PD), suggesting these symptoms may make robust predictors of prodromal PD and PD, respectively.
DISCUSSION
Clinical markers at high specificity for developing PD could be used as tools in the screening of general populations to identify individuals at higher risk of developing PD.
PubMed: 37810617
DOI: 10.3389/fnagi.2023.1232387 -
Frontiers in Veterinary Science 2024MicroRNAs (miRNAs) serve as key regulators in gene expression and play a crucial role in immune responses, holding a significant promise for diagnosing and managing... (Review)
Review
MicroRNAs (miRNAs) serve as key regulators in gene expression and play a crucial role in immune responses, holding a significant promise for diagnosing and managing diseases in farm animals. This review article summarizes current research on the role of miRNAs in various farm animal diseases and mycotoxicosis, highlighting their potential as biomarkers and using them for mitigation strategies. Through an extensive literature review, we focused on the impact of miRNAs in the pathogenesis of several farm animal diseases, including viral and bacterial infections and mycotoxicosis. They regulate gene expression by inducing mRNA deadenylation, decay, or translational inhibition, significantly impacting cellular processes and protein synthesis. The research revealed specific miRNAs associated with the diseases; for instance, gga-miR-M4 is crucial in Marek's disease, and gga-miR-375 tumor-suppressing function in Avian Leukosis. In swine disease such as Porcine Respiratory and Reproductive Syndrome (PRRS) and swine influenza, miRNAs like miR-155 and miR-21-3p emerged as key regulatory factors. Additionally, our review highlighted the interaction between miRNAs and mycotoxins, suggesting miRNAs can be used as a biomarker for mycotoxin exposure. For example, alterations in miRNA expression, such as the dysregulation observed in response to Aflatoxin B1 (AFB1) in chickens, may indicate potential mechanisms for toxin-induced changes in lipid metabolism leading to liver damage. Our findings highlight miRNAs potential for early disease detection and intervention in farm animal disease management, potentially reducing significant economic losses in agriculture. With only a fraction of miRNAs functionally characterized in farm animals, this review underlines more focused research on specific miRNAs altered in distinct diseases, using advanced technologies like CRISPR-Cas9 screening, single-cell sequencing, and integrated multi-omics approaches. Identifying specific miRNA targets offers a novel pathway for early disease detection and the development of mitigation strategies against mycotoxin exposure in farm animals.
PubMed: 38803799
DOI: 10.3389/fvets.2024.1372961 -
Medical Mycology Oct 2023The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our... (Review)
Review
The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients.
Topics: Humans; Aspergillosis; Hematopoietic Stem Cell Transplantation; Fungi; Mycoses; Environmental Monitoring
PubMed: 37793805
DOI: 10.1093/mmy/myad103