Search Results (154)

Vaccine performance in livestock and poultry often varies under field conditions. Conventional explanations, such as handling errors, cold-chain failures, or antigen mismatch do not fully account for inconsistent immunogenicity and durability. Increasing evidence suggests that the gut microbiome acts as an upstream regulator of vaccine responses through microbial structural signals and metabolites that shape antigen presentation, B-cell metabolism, and inflammatory tone. Early life microbiome disruption can impair antibody responses to multiple vaccines, highlighting a plausible causal role for dysbiosis in suboptimal vaccine efficacy. Microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs), can influence B-cell differentiation and antibody production through metabolic and epigenetic pathways. However, these effects are dose- and context-dependent, highlighting the need for controlled translation rather than generalized assumptions that higher SCFA levels are beneficial. This review synthesizes microbiome–immunometabolism pathways relevant to vaccine responses in food animals and assesses practical nutritional and microbiome-targeted strategies, such as amino acids, trace minerals, organic acids, phytogenics, and postbiotics, that may modulate these pathways to improve outcomes. We also propose field-deployable biomarker panels that combine immune readouts with inflammation- and microbiome-linked metabolite proxies to stratify likely responders, monitor intervention effects, and improve trial comparability. Finally, we outline translational study designs that connect microbiome shifts to protective immune endpoints and performance outcomes, enabling evidence-based integration of microbiome-informed strategies into vaccination programs for poultry, with broader conceptual relevance to other food animals. Full article

The COVID-19 pandemic highlighted both the transformative potential of mRNA vaccines and the structural challenges associated with their supply chains. Unlike traditional vaccine platforms, mRNA vaccines depend on highly specialized raw materials, including plasmid DNA (pDNA), nucleotides, enzymes, and lipid nanoparticles (LNP), that are produced by a limited number of global suppliers. These dependencies, combined with platform-specific manufacturing processes and stringent cold chain requirements, introduce vulnerabilities across production, distribution, and regulatory oversight. This narrative review examines the distinctive features of mRNA vaccine supply chains and identifies key challenges and opportunities across three interconnected domains: manufacturing systems, logistics and distribution, and regulatory governance. Drawing on literature published between January 2021 and March 2026, the review synthesizes evidence on supply chain bottlenecks revealed during the COVID-19 pandemic, including upstream raw-material dependencies, limitations in manufacturing scale-up, cold chain constraints, and regulatory fragmentation. Particular attention is given to the implications of these challenges for low- and middle-income countries, where infrastructure, technical capacity, and regulatory resources may limit participation in mRNA vaccine production and deployment. The review also highlights emerging strategies to strengthen supply chain resilience, including diversification of input suppliers, development of regional manufacturing hubs, improvements in vaccine thermostability, regulatory harmonization initiatives, and the use of digital technologies for supply chain management. By integrating insights from manufacturing, logistics, and regulatory perspectives, this study contributes to a better understanding of the structural characteristics shaping mRNA vaccine supply chains and identifies priority areas for strengthening global preparedness for future health emergencies. 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

Background: RNA therapeutics represent a rapidly advancing field with significant potential for treating viral infections and cancer. This review examines the current landscape of RNA-based strategies, including siRNA, miRNA mimics, and antisense oligonucleotides. For viral infections, the focus is on hepatitis B (HBV) and C (HCV), HIV, and SARS-CoV-2. Approaches include targeting viral transcripts directly (e.g., siRNAs against HBV surface antigen) or host factors critical for viral replication (e.g., anti-miR-122 miravirsen for HCV). The successful development of mRNA vaccines for COVID-19 is highlighted as a major breakthrough, demonstrating the feasibility of rapid RNA vaccine deployment. The manuscript reviews several RNA therapeutics in oncology that have reached clinical trials. These include TargomiR (a miR-16 mimic for mesothelioma), cobomarsen (an anti-miR-155 for lymphomas), and MRX34 (a miR-34a mimic for various solid tumours). The review also covers emerging candidates like an miR-221 inhibitor and various strategies for breast cancer, such as targeting Bcl-2, KRAS, and specific miRNAs. A critical challenge across both fields is developing efficient and safe delivery systems, including lipid nanoparticles, GalNAc conjugates, and bacterial minicells. Despite promising preclinical results, clinical translation has been hampered by issues like insufficient delivery efficiency to human tumours, toxicity, and the complex, interconnected regulatory networks of miRNAs, which can lead to unpredictable off-target effects. Conclusions: While RNA therapeutics hold immense promise, overcoming delivery barriers and enhancing understanding of RNA regulatory networks are essential for future success. Full article

Viral hemorrhagic fevers (VHFs) comprise a heterogeneous group of severe infectious diseases that continue to represent a major global health concern. Although many VHFs remain endemic to regions of Africa, Asia, and the Americas, their wide geographic distribution, together with increasing international travel and global trade, facilitates the importation of cases into non-endemic areas and raises the risk of secondary transmission under favorable ecological and epidemiological conditions. These infections are frequently associated with high case-fatality rates and impose a substantial social and economic burden, including pressure on healthcare systems, disruption of essential services, and long-term physical and psychological sequelae among survivors. Despite notable advances in recent years, therapeutic options for VHFs remain limited. Supportive care continues to represent the cornerstone of clinical management for most infections, while pathogen-targeted therapies are available only for a restricted number of diseases. Monoclonal antibody-based therapies have achieved the most significant regulatory success to date, particularly for Ebola virus disease. In parallel, several small-molecule antivirals have been investigated in preclinical and clinical settings, including during outbreak responses, although inconsistent efficacy and safety concerns have limited widespread approval. Vaccine development has progressed further, with licensed vaccines available for selected VHFs, including Ebola, yellow fever, and dengue, and multiple candidates based on diverse technological platforms advancing through clinical evaluation. In addition to summarizing current therapeutic and vaccine strategies, this review highlights pharmaceutical development considerations relevant to biologic therapeutics and selected vaccine platforms, including formulation stability, pharmacokinetic behavior, delivery routes, storage requirements, and logistical constraints affecting deployment during outbreak responses. Using a comparative cross-pathogen framework, the review synthesizes recent literature to identify translational gaps, regulatory challenges, and future priorities for the development of safer and more effective medical countermeasures against VHFs. Full article

West Nile virus (WNV) is a mosquito-borne flavivirus of growing importance for both human and equine health in Europe. Horses are highly susceptible to neurological disease and, because they share ecological exposure with humans, they represent valuable sentinels for detecting local viral circulation within a One Health framework. However, diagnosis of WNV infection in equines is complicated by the short and low-level viraemia, which limits the sensitivity of molecular assays, and by serological cross-reactivity with related flaviviruses and the confounding effects of vaccination. In this narrative review, we summarise the current diagnostic tools for WNV in horses, including direct detection methods (RT-qPCR, virus isolation, antigen detection) and indirect serological approaches (IgM and IgG ELISA, virus neutralisation tests), and discuss their practical performance and constraints in clinical and surveillance settings. We further examine equine surveillance systems, passive clinical reporting, active serosurveys and sentinel cohorts, and their integration with vector, avian and environmental monitoring. Key challenges include methodological heterogeneity, limited access to confirmatory testing and variable cross-sector data sharing. Finally, we outline future directions, highlighting the need for harmonised laboratory protocols, innovative field-deployable diagnostics, genomic surveillance and integrated, multi-source monitoring systems to strengthen early warning capacity and improve preparedness for WNV outbreaks in equine populations. Full article

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk. Full article

African swine fever (ASF) is a contagious viral disease that causes severe economic losses in the global swine industry. Since its introduction to Vietnam in 2019, ASFV has evolved rapidly, with genotype II strains dominating initially and recombinant I/II variants emerging by 2023. Live attenuated vaccines (LAVs) have been developed and commercialized in Vietnam, including ASFV-G-ΔI177L, ASFV-G-ΔI177L/ΔLVR, and ASFV-G-ΔMGF, which confer homologous immune protection. Despite this, LAVs face challenges related to genetic stability, impossible protection against emerging recombinant strains, potential reversion to virulence, viral shedding, and safety in pregnant sows. ASFV’s ongoing evolution underscores the need for continuous genomic surveillance, evaluation of cross-protective efficacy, and implementation of biosecurity and DIVA strategies focused more on evaluating vaccine efficacy than safety. This review summarizes the current molecular epidemiology of ASFV in Vietnam after vaccines were licensed for use, the development and performance of commercial LAVs, and the practical challenges of their application in endemic settings, and provides insights for informed vaccine deployment and integrated ASF control strategies in rapidly evolving viral landscapes. Full article

Artificial intelligence (AI)-enabled unmanned aerial vehicles (UAVs) are rapidly emerging as transformative technologies for sustainable healthcare logistics, particularly in remote and infrastructure-constrained regions. Despite growing implementation, the environmental, social, and governance (ESG) implications of these systems remain insufficiently synthesized in the literature. This study conducts a PRISMA-ScR-guided Systematic Review of 37 peer-reviewed studies selected from 333 records across six major scientific databases (2015–2026). The analysis reveals a sharp acceleration of research after 2021, with over 80% of publications produced between 2021 and 2024, indicating increasing global interest in AI-supported autonomous medical logistics. Evidence demonstrates that AI-enabled drones can substantially reduce delivery times; expand access to blood, vaccines, and essential medicines; and enhance emergency response capacity in rural and disaster-affected environments. From a sustainability perspective, AI-driven route optimization and autonomous navigation may reduce transport-related emissions, supporting climate-responsive healthcare supply chains. However, large-scale deployment remains constrained by regulatory fragmentation, cybersecurity risks, operational limitations, and challenges with social acceptance. This review proposes an ESG-oriented framework linking technological innovation, ethical governance, and equitable healthcare access while identifying key research gaps in lifecycle sustainability assessment, cost-effectiveness modeling, and real-world implementation aligned with the Sustainable Development Goals (SDGs). Full article

Pandemic influenza remains a persistent global threat with the potential to cause widespread morbidity, mortality, and economic disruption. Despite decades of preparedness efforts, current influenza vaccine systems remain constrained by long production timelines, early strain-selection requirements, and limited flexibility once a pandemic is underway. The COVID-19 pandemic fundamentally reshaped expectations for vaccine development and deployment, demonstrating that platform-based technologies, particularly messenger RNA (mRNA) vaccines, can deliver safe and effective vaccines at unprecedented speed when supported by regulatory readiness, manufacturing capacity, and coordinated public–private investment. Drawing on lessons from COVID-19, recent Phase III clinical trial data for seasonal influenza mRNA vaccines, and global preparedness initiatives such as the 100 Days Mission, this expert perspective examines how mRNA and other next-generation vaccine technologies could strengthen preparedness for a future influenza pandemic. It reviews evidence related to platform speed, clinical performance, manufacturing adaptability, regulatory pathways, and global access, while also highlighting emerging scientific frontiers, including artificial intelligence–augmented immunogen design and innovations in vaccine delivery. It argues that sustained investment in adaptable vaccine platforms, coupled with advances in delivery, manufacturing, and data-driven design, will be critical to improving global readiness and reducing the impact of the next influenza pandemic. Full article

Extreme hydro-meteorological events are intensifying under climate change, disproportionately disrupting last-mile healthcare in flood-prone geographies. In this study, flood-adaptive primary care clinics (FAPCCs) integrated with islandable smart microgrids and a rapid-deploy medical technology stack (MedTech) are developed and evaluated to ensure continuity of essential services (triage, maternal and child health, vaccination cold-chain, minor procedures, diagnostics, and telemedicine) during fluvial, pluvial, and coastal flooding. Evidence on resilient health facilities, microgrid architectures, distributed energy resources, and modular clinical systems is presented in a multi-layer systems design: (1) a modular, amphibious, and elevatable clinic chassis; (2) a photovoltaic–battery–diesel hybrid system with demand-aware energy management; (3) redundant connectivity long-term evolution/fifth-generation, satellite, and very high frequency; (4) a rapid-deploy MedTech kit including point-of-care diagnostics, low-temperature cold-chain, negative-pressure isolation, and sterilization modules; and (5) flood-aware logistics using unmanned aerial vehicle/unmanned surface vehicle. A mixed-integer linear programming sizing is formulated and dispatched with a continuity-of-care reliability metric that couples energy availability to clinical throughput. Simulation across three archetypal sites (peri-urban delta, inland riverine, coastal estuary) shows that FAPCCs achieve the service availability of higher than 99.5% across 7-day grid outage scenarios while reducing fuel use by 62–81% relative to diesel-only baselines, maintaining vaccine temperatures within 2–8 °C with <0.1% thermal excursion time, and sustaining telemedicine quality of service with <150 ms median uplink latency in hybrid networks. A life-cycle cost analysis indicates a 7.1–9.8 year discounted payback from fuel displacement and avoided service loss. Deployment playbooks and policy guidance are also proposed for Ministries of Health and Disaster Agencies in monsoon-impacted regions. Full article

Poliovirus (PV), a historically significant enterovirus responsible for severe paralytic diseases, has seen its incidence dramatically reduced through widespread vaccination efforts, propelling global eradication initiatives. Despite the success of traditional oral poliovirus vaccines (OPVs) and inactivated poliovirus vaccines (IPVs), challenges such as vaccine-derived virus reversion and biosafety concerns during vaccine production persist. Virus-like particle (VLP) vaccines, which mimic native viral structures without containing viral genomes, offer enhanced safety profiles and robust immunogenicity, positioning them as promising candidates for next-generation poliovirus vaccines, especially in the post-certification era. This review systematically summarizes current progress in poliovirus VLP vaccine research, including the diverse expression systems employed for VLP production, strategies for peptide assembly and stabilization, and evaluations of antigenicity and immunogenicity. Additionally, it highlights structural analyses utilizing cutting-edge cryo-electron microscopy. By integrating recent developments in genetic engineering, structural biology, and immunology, this article discusses the advantages and challenges associated with poliovirus VLP vaccines and explores future directions aimed at supporting the global goal of a poliovirus-free world. This comprehensive overview aims to provide a theoretical foundation and technical guidance to facilitate the development and deployment of safer and more effective poliovirus vaccines. Full article

Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling have substantially expanded the experimental evidence, while generative artificial intelligence now enables de novo design of peptide immunogens and multi-epitope antigens under precisely controlled constraints. This review approaches how these complementary developments are transforming peptide vaccine research, moving beyond classical reverse vaccinology and conventional epitope prediction toward integrated, data-driven design frameworks. We discuss key generative model architectures and conditioning strategies aligned with vaccine objectives, including approaches that account for structural presentation, antigen processing and population-level human leukocyte antigen (HLA) diversity. Central to this perspective is the requirement for rigorous experimental validation and for strengthening the computational–experimental feedback loop through iterative in vitro and in vivo testing informed by systems-level immune readouts. We highlight representative applications spanning infectious diseases, cancer immunotherapy and vector-borne vaccinology, and we outline major technical and translational challenges that must be addressed to enable robust real-world deployment. Finally, we propose future directions for precision peptide vaccinology, emphasizing standardized functional benchmarks, the development of richer curated datasets linking sequence space to immune outcomes, and the early incorporation of formulation and delivery constraints into generative design pipelines. Full article

Avian influenza (AI), particularly highly pathogenic avian influenza (HPAI), represents a serious and growing threat to global poultry production, international trade, and human health security. Control of AI is complicated by the high evolutionary rate of influenza A viruses, which drives antigenic diversity and ongoing emergence of novel strains. Effective surveillance and disease management therefore depend on timely and accurate diagnostics. While conventional methods—including virus isolation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assays (ELISAs)—remain effective and widely used, they are limited by long turnaround times, the need for specialized equipment, and reliance on highly trained personnel. In addition, strict state and federal regulatory requirements restrict testing to a limited number of authorized laboratories. Although these regulations are essential for maintaining diagnostic accuracy and quality assurance, they place substantial strain on laboratory capacity during outbreaks and delay actionable results. The need for rapid, on-site decision making has driven interest in alternative diagnostic approaches, including biosensor technologies. A major limitation of current diagnostic strategies is the lack of robust DIVA (Differentiating Infected from Vaccinated Animals) capability. In countries such as the United States, where poultry vaccination against AI is not routinely practiced, the absence of DIVA-compatible diagnostics has hindered adoption of vaccination as a disease management tool, as seropositive birds and products face significant trade restrictions. Biosensor platforms capable of enabling DIVA strategies offer a potential pathway to support vaccination while preserving surveillance integrity. This review examines the current landscape of AI and HPAI diagnostics, emphasizing the limitations of traditional approaches and the opportunities presented by biosensor platforms. We evaluate electrochemical, optical, piezoelectric, and nucleic-acid-based biosensors, with particular attention to biorecognition strategies, performance metrics, field deployability, and applications supporting subtype discrimination, DIVA implementation, and One Health surveillance. Full article

Ovarian cancer (OC) is a particularly lethal gynecological malignancy with few treatment options due to its late-stage diagnosis, extensive genetic heterogeneity, and frequent development of resistance to existing therapies. Immunotherapy has revolutionized the management and clinical outcome of numerous solid tumors, but its clinical benefit for OC has been limited, in part due to an extremely immunosuppressive tumor microenvironment (TME) and diverse, overlapping immune evasion mechanisms. In this review, we present a comprehensive and timely synthesis of next-generation immunotherapeutic approaches for ovarian cancer, emphasizing strategies that overcome the immunosuppressive tumor microenvironment and improve clinical responsiveness. We describe the emerging molecular mechanisms of immune evasion in OC, including altered antigen presentation, inhibition of T-cell activation (e.g., via immunological checkpoints, metabolic reprogramming), polarization of tumor-associated macrophages (TAMs), and dysfunction of natural killer (NK) cells. We also critically examine several emerging therapeutic approaches, including combination immune checkpoint blockade (ICB), bispecific T-cell engagers (BiTEs), neoantigen-based vaccines, chimeric antigen receptor (CAR)-T- and CAR-NK-cell therapies, oncolytic viruses (OVs), and nanoparticle-mediated immunomodulation. In addition, we highlight recent advances in tumor microenvironment–targeted therapies for ovarian cancer, focusing on strategies that modulate non-lymphoid components such as cancer-associated fibroblasts (CAFs), hypoxia-driven signaling, and the PI3K/AKT/mTOR axis to enhance antitumor immune responsiveness. Finally, we discuss how predictive biomarkers, multi-omics systems, and patient-derived organoid models are accelerating the development and deployment of precision immunotherapies for OC. We would like to highlight the translational promise of next-generation immunotherapies and identify novel molecular targets that may be leveraged to achieve durable responses in OC. Full article