Search Results (278)

Bacterial chondronecrosis with osteomyelitis (BCO) is a major cause of lameness in modern broiler chickens. It remains a persistent challenge in the broiler industry, resulting in substantial economic losses and serious animal health concerns. The pathogenesis of BCO involves rapid muscle growth, resulting in disproportionate body weight relative to skeletal maturity, thereby increasing mechanical stress and leading to microfractures and osteochondrotic clefts in the proximal growth plates of the femora and tibiae. Infection progresses via hematogenous dissemination and colonization of the leg bones by opportunistic pathogens, primarily Staphylococcus spp., Enterococcus spp., and Escherichia coli, originating from the gastrointestinal or respiratory tract, leading to chronic inflammation, ischemia, biofilm formation, and progressive bone necrosis. Control strategies, including selective breeding, enhanced management and production practices, nutritional interventions, and the administration of antimicrobial agents, offer partial mitigation but have failed to provide a permanent solution to BCO incidence. Vaccination is one of the most promising and targeted immunological approaches to enhance the host immune responses against bacterial pathogens. Electron beam (eBeam) inactivated vaccines represent a significant advancement among available vaccination strategies. This review leverages current knowledge of the etiology, pathophysiology, control measures, and the use of eBeam technology (EBT) in vaccine development to provide a scientifically grounded and innovative approach to controlling BCO-associated lameness in broiler chickens. This article also provides insights into future directions for integrated, antibiotic-free strategies to mitigate BCO and revenue losses, enhance broiler welfare, ensure consumer safety, and support the long-term sustainability of the global poultry industry. Full article

Patients with multiple myeloma (MM) exhibit profound immune dysregulation, predisposing them to severe outcomes following SARS-CoV-2 infection. Current evidence highlights shared immunopathological mechanisms linking MM and COVID-19, with particular emphasis on the interleukin-6 (IL-6) axis as a shared amplifier of inflammation rather than the sole driver of disease. MM is characterized by a baseline pro-inflammatory milieu, in part mediated by IL-6, which is further amplified during SARS-CoV-2 infection, resulting in cytokine escalation, complement activation, coagulopathy, and multi-organ injury. This amplification operates within a broader, redundant network that also includes T-cell exhaustion, NK-cell dysfunction, checkpoint signaling, complement and endothelial injury, and treatment-induced immune defects. This overlap provides a mechanistic basis for the disproportionately high morbidity and mortality observed in this population. Even with advancements in vaccination, antiviral therapy, and clinical practice, patients with MM who exhibit impaired vaccine responses, active disease, or treatment-related immune dysfunction continue to experience considerable vulnerability to COVID-19. In addition, MM patients demonstrate suboptimal vaccine-induced immune responses, contributing to persistent vulnerability to severe and breakthrough infections. Modern MM therapies, including anti-CD38 antibodies, BCMA-directed agents, and bispecific T-cell redirecting antibodies, further reshape antiviral immunity by reducing NK cells, inducing plasma cell aplasia, causing hypogammaglobulinemia, and impairing T-cell function. Emerging treatment approaches targeting this shared pathway have been explored, with a focus on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). EVs exhibit multimodal properties, including suppression of pro-inflammatory cytokines, restoration of immune homeostasis, inhibition of viral entry, and promotion of tissue repair and regeneration. Early clinical experience in severe COVID-19 populations suggests a favorable short-term safety profile; reported efficacy, however, derives from small, largely uncontrolled or early-phase studies, and the single randomized trial reporting a mortality benefit did so only in an exploratory post hoc subgroup, with its pre-specified primary endpoint not met. Overall, EVs constitute a biologically plausible but as yet unproven adjunctive strategy that warrants further investigation. Critically, no MM patient has ever been enrolled in an EV trial; current rationale for EV use in MM is therefore extrapolated entirely from non-MM populations, and no MM-specific data exist. Difficulties such as EV heterogeneity, manufacturing variability, uncertain pharmacokinetics, limited targeting efficiency, and potential prothrombotic effects must be resolved before their application in MM-specific clinical settings. Full article

Lawsonia intracellularis, the etiologic agent of porcine proliferative enteropathy (PPE), represents a growing challenge for modern swine production systems. The infection often occurs in a subclinical form and, together with limited awareness of its true production impact, may delay diagnosis and the timely adoption of control measures. In our opinion, this under-recognition of subclinical infection represents the greatest barrier to successful PPE control. Disease management is further complicated by frequent co-infections, limitations of currently available diagnostic tools, and the progressive reduction in routine antimicrobial use, which has revealed the true burden of PPE under commercial conditions. We therefore argue that vaccination should no longer be considered a stand-alone preventive measure, but rather the cornerstone of an integrated, farm-specific management strategy combining accurate diagnostic interpretation, optimized production flows, biosecurity, nutritional management, and continuous veterinary–farmer collaboration. Drawing on both published evidence and the long-term field experience of the authors, this Opinion discusses the key challenges limiting effective PPE control and proposes a practical framework to improve disease recognition, prevention, and sustainable management under commercial production conditions. Full article

Background: Influenza viruses can cause mild to severe illnesses. The burden of disease varies widely depending on multiple factors, including the type and subtype of circulating viruses, timing of the season, flu vaccine efficacy and vaccination rates. Influenza viruses are also highly prone to genetic change and rapid spread due to modern human movement patterns, making influenza surveillance vital for public health awareness, guidance, policy, disease mitigation, and annual recommendations on vaccine composition. Methods: A network of three National Influenza Reference Centers (NIRCs) was established in the United States more than 10 years ago to support the Centers for Disease Control and Prevention’s (CDC) Influenza Division with its national influenza surveillance efforts. Located in California, New York, and Wisconsin, they are funded by CDC via a collaborative agreement with the Association of Public Health Laboratories (APHL). The role of the NIRCs is critical to national and global influenza surveillance, providing rapid information on circulating influenza strains from three arms of laboratory testing: (1) the virus isolation project (VIP), (2) next-generation sequencing (NGS), and (3) anti-viral drug resistance testing. Results: Here, we review the data generated in the VIP lab of the New York State (NYS) NIRC before, during, and after the COVID-19 pandemic and discuss its utility in an understanding of disease dynamics and viral evolution, as well as public health policy and decision making during this historic period in health care. Conclusion: Continued preparedness and surveillance are critical to mitigating the impact of evolving influenza viruses. Full article

The Oropouche virus (OROV), an orthobunyavirus primarily transmitted by the biting midge Culicoides paraensis, is the causative agent of Oropouche fever, a re-emerging arboviral disease associated with significant morbidity in Central and South America. The increasing frequency of outbreaks, including cases of sustained transmission in non-endemic regions and reports of vertical transmission, highlights the growing public health concern posed by OROV. Currently, there are no specific antiviral therapies or licensed vaccines available, underscoring the urgent need for effective therapeutic and preventive strategies. Recent advances in antiviral research have identified promising candidates, including repurposed drugs and bioactive compounds that target key stages of the viral replication cycle. In parallel, vaccine development has progressed through modern platforms, including viral vector-based and nucleic-acid-based technologies, enabling rapid responses to emerging outbreaks. However, major challenges remain, particularly due to the limited understanding of OROV pathogenesis, virus–host interactions, and the correlates of protective immunity. Furthermore, the ongoing evolution of OROV, including the genetic diversity and potential genomic rearrangements observed among circulating strains, represents an additional challenge that may influence viral characteristics and potentially affect the long-term efficacy of antiviral interventions and vaccine-induced protection. This review summarizes recent advances in the discovery of antiviral candidates and the development of vaccine approaches against OROV, both of which are essential for reducing the impact of OROV infections and strengthening preparedness for future outbreaks. Full article

Avian orthoreovirus (ARV) has re-emerged as one of the most important viral pathogens affecting modern poultry production worldwide. In China, the epidemiological landscape of ARV has undergone a substantial transformation over the past decade, characterized by increasing genotypic diversity, frequent genome reassortment, an expanding host range, and recurrent vaccine-breakthrough outbreaks. Growing evidence indicates that contemporary ARV populations evolve within a dynamic multispecies transmission network shaped by intensive poultry production, host adaptation, and vaccine-associated selective pressures. Recent molecular studies have revealed extensive genetic heterogeneity among circulating strains and highlighted the limitations of conventional σC-based classification systems for accurately describing viral evolution, pathogenicity, and antigenic diversity. Whole-genome analyses further demonstrate that reassortment among chicken-origin, duck-origin, and goose-origin orthoreoviruses plays a pivotal role in generating novel viral variants with altered biological properties. In parallel, accumulating evidence suggests that ARV exerts broad immunomodulatory effects through the disruption of innate antiviral signaling, impairment of lymphoid organ function, interference with vaccine responsiveness, and the enhancement of susceptibility to secondary infections. These findings indicate that ARV should be regarded not only as an arthrotropic pathogen but also as an important immunopathological agent influencing flock health and productivity. This review summarizes current knowledge of ARV in China, with an emphasis on molecular epidemiology, genomic evolution, reassortment mechanisms, transmission ecology, immune interference, vaccine escape, and integrated prevention strategies. Particular attention is given to the increasing importance of whole-genome surveillance, phylodynamic analysis, and multispecies epidemiological monitoring for understanding contemporary ARV evolution. Future perspectives involving structural vaccinology, precision immunization, metagenomics-assisted surveillance, and predictive evolutionary modeling are also discussed. Collectively, sustainable ARV control will likely require genome-informed and adaptive prevention frameworks integrating virology, immunology, epidemiology, and precision poultry management. Full article

Porcine group A rotavirus (PoRVA) is a significant cause of viral diarrhea in piglets, necessitating urgent global implementation of effective control strategies. This review assesses advancements in PoRVA in vitro cultivation and amplification, crucial for PoRVA vaccine development. Traditional PoRVA cultivation commonly employs primary porcine kidney cells or finite cell lines like MA-104, posing well-documented challenges in scalability, production cost, and their ability to recapitulate the natural intestinal microenvironment. Consequently, research has increasingly focused on adapting PoRVA to alternative systems, particularly immortalized porcine cell lines or physiologically relevant porcine intestinal organoids. This adaptation process, involving serial passaging, can induce genomic alterations and virulence attenuation in piglets, essential for generating live attenuated vaccine (LAV) candidates. Modern biotechnological tools, such as reverse genetics and synthetic genomics, have expedited the creation of recombinant PoRVA strains with defined antigenic profiles and enhanced in vitro growth characteristics. However, a significant concern regarding LAV candidates derived from cell culture adaptation is the risk of virulence reversion upon pig back-passage, necessitating thorough safety and genetic stability evaluations. Nevertheless, utilizing stable cell lines or organoid platforms presents a feasible and cost-effective approach for large-scale PoRVA vaccine production. Future research should focus on identifying vaccine candidates that provide broad protection and exceptional safety, with an emphasis on cross-protection against divergent epidemic genotypes, while ensuring the economic feasibility of innovative manufacturing approaches. Full article

Ribonucleic acid-based vaccines have emerged as one of the most significant advances in modern vaccine development, demonstrating remarkable clinical success and enabling rapid responses to emerging infectious diseases. Despite their therapeutic potential, the development of these vaccines remains challenging because of the inherent instability of ribonucleic acid molecules, their susceptibility to degradation, and the complexity of formulation design. Ensuring product quality, stability, and biological performance therefore requires comprehensive analytical characterization throughout development, manufacturing, storage, and quality control. This review provides a comprehensive overview of current analytical strategies used to evaluate ribonucleic acid-based vaccine formulations. Key analytical approaches for assessing molecular integrity, purity, encapsulation efficiency, particle morphology, size distribution, surface characteristics, structural attributes, and biological potency are discussed. The review also examines the influence of formulation composition, lipid nanoparticle design, manufacturing processes, and storage conditions on vaccine stability and performance. In addition, major degradation pathways, critical quality attributes, and analytical challenges associated with quality assessment are highlighted. Furthermore, current regulatory considerations and limitations of existing analytical methodologies are discussed, particularly the challenges associated with establishing robust relationships between physicochemical properties and biological efficacy. The review emphasizes the importance of integrated multi-method analytical approaches for comprehensive characterization and quality assurance. Continued advances in analytical technologies and standardization efforts will be essential for supporting the development of safe, effective, and stable ribonucleic acid-based vaccines and for facilitating their broader pharmaceutical applications. Full article

Dengue virus infection is a febrile illness caused by the Orthoflavivirus Dengue, which is transmitted by the mosquitoes Aedes aegypti or Aedes albopictus. Despite the fact that Dengue virus (DENV) is present in tropical and subtropical areas, climate change with global warming has been associated with the spread of Aedes aegypti and Aedes albopictus mosquitoes in several other regions worldwide. Notably, as the presence of Aedes albopictus has been confirmed in Southern Europe, already locally transmitted cases of Dengue virus infection have been reported in Europe. Apart from Europe, Australia has reported DENV cases in the 21st century that have been associated with the transmission of Aedes aegypti in the neighboring islands. Climate change, namely increasing temperatures, higher humidity and rainfalls, together with the development of urban heat islands, uncontrollable deforestation and urbanization, travelling and trade, has contributed significantly to the spread of DENV infection. Modern diagnosis based upon the advent of “multi-omics” techniques and machinery learning programs will be of the utmost importance for the early and accurate diagnosis of DENV infection. Finally, preventive measures for controlling Dengue virus infection, such as the use of repellents, educational programs, and improvement in water storage and waste management at the community levels would be very useful. Regarding climate change, the One Health Approach by integrating collaboration of various sectors and raising public awareness seems to be of the utmost importance in this context. Further investigations regarding the development of antiviral agents and vaccines will be an important asset in our armamentarium against DENV infection. Full article

Vaccination remains one of the most effective strategies for preventing infectious diseases. Yet, the success of modern vaccines increasingly depends on the rational design of adjuvants that enhance and shape immune responses. In this review, we examine current and emerging adjuvant strategies for viral vaccines across the human lifespan. Traditional adjuvants, particularly aluminum salts, have long served as the foundation of vaccine formulations. Still, their limitations have driven the exploration of novel platforms, including emulsions, nucleic acid-based adjuvants, and advanced particulate delivery platforms with intrinsic immunostimulatory properties. These newer approaches act through diverse mechanisms, such as activating innate immune pathways via pattern recognition receptors (PRRs) and stimulating antigen-presenting cells (APCs), thereby improving both humoral and cellular immunity. Recent advances in molecular biology, nanotechnology, and systems vaccinology have deepened mechanistic understanding and enabled more precise modulation of immune responses. However, significant challenges remain, including incomplete knowledge of adjuvant mechanisms, limited diversity among licensed adjuvants, safety concerns, and inconsistent efficacy across age groups. In particular, immune immaturity in infants and immunosenescence in older adults highlight the need for age-specific adjuvant strategies. The review identifies critical gaps in comparative studies, long-term safety data, and the development of adjuvants capable of inducing broad and durable immunity. Further, this article integrates licensed and emerging viral vaccine adjuvants through a lifespan framework. Addressing these limitations through interdisciplinary research and precision-based approaches will be essential for advancing next-generation vaccines and improving global preparedness for emerging infectious diseases. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article

Melanoma adjuvant therapy has substantially improved recurrence-free and distant metastasis-free survival in patients with resected high-risk disease, and more recently, these advances have extended to earlier stages. However, important unmet needs remain, including the management of stage IIIA disease, the optimal treatment strategy after relapse on adjuvant therapy, and the identification of biomarkers capable of refining patient selection. This review summarizes recent advances and unresolved questions in the adjuvant and neoadjuvant treatment of melanoma. We discuss novel systemic strategies, including immune checkpoint inhibitor combinations and personalized neoantigen mRNA vaccines, together with the expanding role of neoadjuvant approaches. We also examine prognostic and predictive tools—such as clinicopathologic models, circulating tumor DNA, serum biomarkers, tumor microenvironment features, and gene expression profiling—that may help better define recurrence risk and therapeutic benefit. Current evidence suggests that although modern therapies have changed the natural history of resected melanoma, a substantial proportion of patients are still overtreated or undertreated when treatment decisions are based on stage alone. Future progress will depend on integrating biological risk stratification with clinical staging and optimizing treatment sequencing across adjuvant and neoadjuvant settings. Full article

Brucellosis remains one of the most widespread zoonotic infections worldwide, causing serious veterinary, medical, and socio-economic consequences. The disease, caused by bacteria of the genus Brucella, affects a wide range of domestic and wild animals as well as humans, with global incidence potentially reaching 1.6–2.1 million new cases annually. The most effective approach to combating brucellosis is specific prevention through vaccination. Therefore, we conducted this review to summarize data from existing studies on modern strategies for brucellosis vaccination, types of vaccine platforms, their efficacy, safety, and applicability in veterinary and human medicine. We searched databases including PubMed, Scopus, and Web of Science to identify relevant scientific articles in English published from 1990 to 2025. The aim of this work is to conduct a systematic analysis of modern brucellosis vaccination strategies in livestock and humans, as well as to evaluate the prospects of new vaccine platforms. The review examines live attenuated, inactivated, subunit, vector, and DNA vaccines, as well as their immunological mechanisms of action, advantages, and limitations of application. This information allows for a better understanding of the mechanisms of protective immunity formation and challenges related to DIVA diagnostics (Differentiating Infected from Vaccinated Animals). The “One Health” concept demonstrated the interconnection between human, animal, and environmental factors, emphasizing the need for an interdisciplinary approach to brucellosis monitoring, prevention, and control. Vector vaccines based on influenza virus (Flu-BA), developed in Kazakhstan, have shown high promise, combining immunogenicity, protective efficacy, and a favorable safety profile. Promising directions remain mRNA vaccines, nanoparticles, CRISPR/Cas9 technologies, and mucosal vaccines. Full article

Background: Liberia modernized vaccination data systems in 2023–2025 by piloting a District Health Information System (DHIS2)-based Digital Vaccination Registry (Electronic Immunization Registry, EIR) to address the limitations of paper-based workflows and of a proprietary COVID-19 electronic platform (offline gaps, lack of unique identifiers, performance issues and cost). Objective: To assess a pilot platform by evaluating training, registry use and device management, utility for routine immunization, vaccine logistics and Adverse Events Following Immunization (AEFI) data, and routine immunization data quality in the DHIS2 mobile application compared with paper registers. Methods: Using the Public Health Informatics Institute’s Collaborative Requirements Development Methodology, stakeholders defined requirements, trained users and implemented a pilot. Mixed methods were used; a mini data audit was performed, and qualitative data were collected across 19 facilities in Montserrado, Gbarpolu and Grand Bassa. Seventy-eight health workers were trained to use the DHIS2 mobile application. Results: The future state design replaces paper aggregation steps with real-time mobile entry to a national registry and dashboard. Dual entry persisted during high-volume periods. The mini data audit found discrepancies between facility paper registers and DHIS2-EIR entries for child enrollment data and, Bacillus Calmette Guérin and Diphtheria–Pertussis–Tetanus dose administration records Participants attributed these discrepancies to internet and device problems and challenges navigating the system. Participants requested a training manual, improved connectivity at point of service, integration with supportive supervision, additional staff and system features (field to record hospital number, automated next visit date, and vaccination status prompts). Conclusions: Lessons from the pilot will inform country-wide implementation, including planned linkage with electronic birth and death registration to enable a unique child identifier and reduce manual errors and delays. Full article

Avian reovirus (ARV) is a ubiquitous pathogen in commercial poultry, traditionally associated with viral arthritis, malabsorption syndrome, and growth retardation. In recent years, the rapid genetic diversification of ARV has raised increasing concerns regarding vaccine mismatch, immune dysregulation, and complex disease outcomes in vaccinated flocks. In this study, an integrated investigation combining large-scale field surveillance, molecular characterization, and controlled animal experiments was conducted to elucidate the epidemiological features of ARV and its impact on heterologous vaccine-induced protection. Epidemiological surveillance revealed widespread ARV circulation in commercial poultry flocks, with marked genetic divergence between contemporary field isolates and classical vaccine strains. Phylogenetic analysis based on the σC gene demonstrated that the majority of circulating strains clustered within emerging genotypes that were genetically distinct from vaccine-related lineages. Using a controlled infection–vaccination–challenge model, prior ARV infection was shown to significantly impair humoral immune responses induced by an inactivated Aviadenovirus hydropericardii (fowl adenovirus serotype 4, FAdV-4) vaccine, as evidenced by reduced FAdV-4-specific antibody levels. Importantly, ARV pre-infection compromised vaccine-mediated protection and was associated with enhanced FAdV-4 pathogenicity following challenge, resulting in increased mortality, aggravated clinical manifestations, and more pronounced pathological lesions. These findings indicate that prior ARV infection is associated with reduced FAdV-4 vaccine-induced humoral responses and partial loss of protective efficacy under controlled experimental conditions. Importantly, this study provides quantitative experimental evidence using a defined infection–vaccination–challenge interference model rather than proposing a previously unrecognized virus-virus interaction. These results underscore the necessity of enhanced ARV surveillance and optimized immunization strategies in modern poultry production systems. Full article