Search Results (6,384)

Pancreas disease (PD), caused by Salmonid alphavirus (SAV), is a notifiable disease in Atlantic salmon (Salmo salar L.) in Norway. Conventional inactivated virus vaccines have shown variable effects in mitigating the disease, and a DNA vaccine has been used over the last 7–8 years, which may have resulted in the reduction in the number of reported PD cases. This manuscript provides a comprehensive overview of DNA vaccination in farmed fish, with a focus on the licensed DNA vaccine, Clynav^®, against SAV3 infection. It explores the biological underpinnings of SAV infection, immune mechanisms activated by DNA vaccines, and the benefits and limitations of this approach. Although antigen processing and presentation mechanisms following DNA vaccination in fish remain incomplete, studies document robust innate responses and measurable adaptive immunity, including neutralizing antibodies, as seen in Clynav, and transcriptomic studies indicate that cell-mediated immunity is evoked under experimental conditions. Comparative trials demonstrate that DNA vaccination reduces viral load, tissue pathology, and, potentially, viral transmission, outperforming traditional oil-adjuvanted vaccines. Additionally, DNA-vaccinated fish show improved growth performance under field conditions. These findings support DNA vaccination as a promising strategy for controlling PD in salmon aquaculture, with implications for fish health, welfare, and sustainable production. Full article

Background: The 2025 EPI Managers’ Meeting for West African countries in Guinea was a critical platform for EPI managers to make an in-depth analysis of immunization programmes. We present a structured analysis of immunization status in West Africa using a WHO Health System model to move beyond descriptive reporting toward systemic analysis for actionable solutions. Methods: The meeting convened EPI managers from 14 of the 17 West African countries and partners supporting the immunization program. Country and regional presentations, immunization and surveillance data and meeting discussions were analysed through a framework identifying (1) core problems, (2) systemic barriers using WHO health systems building blocks and (3) actionable recommendations or call for action. Results: Analysis revealed stagnating immunization coverage. Recovery from COVID-19 pandemic disruptions remained limited, with persistent outbreaks of vaccine-preventable diseases (VPD). Among the five Immunization Agenda 2030 objectives assessed, only Maternal and Neonatal Tetanus (MNT) elimination was on track. Four critical challenges emerged: (1) Routine immunization stagnation with DTP3 median coverage of 76%. This was associated with challenges related to poor data quality, weak implementation of innovative vaccination strategies and donor dependency, as 88.2% of countries financed less than 50% of routine vaccine costs domestically. (2) Sub-optimal progress in Big Catch-Up (BCU) implementation in some countries, revealing poor health system resilience. (3) Inability to sustain high coverage for new vaccine introductions despite significant progress, highlighting demand and service delivery gaps. (4) Persistent VPD outbreaks with geographical expansion and the resurgence of diphtheria epidemics since 2023. Conclusions: Persistent immunization challenges in West Africa appear to reflect interconnected systemic challenges, suggesting the need for a fundamental shift toward subnational strategies, integration of immunization services within primary health care (PHC) and improved data quality. Sustainable financing of the national EPI and acceleration of local vaccine manufacturing is essential to achieve immunization sovereignty in West Africa. Country Call for Action provides strategic guidance to reverse the trend toward the Immunization Agenda 2030 targets. Full article

Fungal β-1,3-glucans are structurally conserved polysaccharide components of the fungal cell wall that exhibit potent immunomodulatory activity. These molecules are recognized by pattern recognition receptors, Toll-like receptors, complement receptor 3, lactosylceramide, scavenger receptors, and EphA2. Binding of β-1,3-glucans through these receptors triggers coordinated innate and adaptive immune responses such as cytokine production, phagocytosis, and trained immunity. In addition to receptor-mediated immune activation, dietary β-1,3-glucans function as fermentable prebiotic fibers that modulate gut microbiota composition, increase short-chain fatty acid production, and strengthen epithelial barrier integrity. These combined immunological and microbiome-mediated effects position β-1,3-glucans as key regulators of gut homeostasis. Preclinical and emerging clinical evidence supports broad therapeutic potential across multiple disease domains, including inflammatory bowel disease, metabolic disorders, respiratory infections, and cancer. In oncology, β-1,3-glucans enhance anti-tumor immunity, improve responses to monoclonal antibodies and chemotherapy, and serve as promising adjuvants in vaccine-based strategies. Additionally, β-1,3-glucan is widely used as a biomarker for invasive fungal infections and represents a validated target of antifungal therapies such as echinocandins. Despite these advances, clinical translation remains limited by heterogeneity in glucan source, structure, and formulation, as well as a lack of appropriately powered, standardized human clinical trials. Future efforts should focus on clarifying mechanisms of action, as well as rigorous clinical evaluation, to fully define the therapeutic utility of fungal β-1,3-glucans. Full article

Biologic and targeted synthetic therapies have substantially improved the management of autoimmune diseases (ADs), achieving unprecedented disease control. However, by modulating key immune pathways, these agents increase susceptibility to a wide spectrum of infections. This narrative review synthesizes current evidence on infectious risks associated with biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in AD, characterizing infection profiles across different drug classes, identifying patient- and treatment-related risk factors, and providing evidence-based recommendations for screening, prevention, and management. A comprehensive literature search was conducted through March 2026, across PubMed, Embase, and the Cochrane Library, using predefined search terms combining biologic and targeted synthetic drug classes with infection-related outcomes. Evidence from major international registries (BSRBR-RA, DANBIO, RABBIT) and society guidelines (ACR, EULAR, IDSA) was prioritized. Among bDMARDs, TNF-α inhibitors (TNF-α i) and rituximab were associated with the highest rates of serious infections, whereas IL-17 and IL-23 inhibitors demonstrated comparatively lower infectious risk profiles. Steroids, older age, and prior serious infections emerged as the most consistent patient-related risk modifiers. Unlike prior reviews focused on single diseases or drug classes, this work provides an integrated, cross-disciplinary risk stratification framework. bDMARDs and tsDMARDs remain among the most innovative treatments available for effective management of ADs, with favorable benefit–risk profiles when accompanied by systematic prevention strategies. Universal pre-treatment screening for tuberculosis and viral hepatitis, risk-stratified parasitic screening, evidence-based vaccination, and selective antimicrobial prophylaxis can mitigate infectious complications. Full article

Between 2020 and 2025, Europe has faced multiple interacting public health threats shaped by and following the COVID-19 pandemic. Alongside COVID-19, the region experienced other infectious disease events, including monkeypox, measles resurgence, legionellosis and acute hepatitis of unknown origin in children. At the same time, non-communicable disease burdens, including obesity, type II diabetes mellitus, disruption of chronic disease care, mental health disorders and increased problematic digital use, intensified during and after the pandemic period. Antimicrobial resistance (AMR) remained a major cross-cutting threat because it undermines the effective treatment of infections and weakens emergency preparedness. This narrative review synthesizes peer-reviewed articles and selected reports from international organizations for the 2020–2025 period, using COVID-19 as the organizing context for examining interconnected infectious, chronic and system-level threats. Across these topics, recurring themes included vaccination gaps, fragmented surveillance, disruption of routine care, health system inequities, misinformation and insufficient preparedness for cross-border threats. The review supports integrated surveillance, continuity plans for essential services, stronger vaccination and risk-communication strategies and sustained AMR stewardship within a One Health framework. Coordinated action across public health, primary care, mental health and chronic disease policy is essential for future resilience. Full article

Therapeutic cancer vaccines are a promising immunotherapy approach in genitourinary (GU) cancers, designed to stimulate antitumor immune responses through antigen-specific T-cell activation. Although agents such as bacillus Calmette–Guérin in bladder cancer and sipuleucel-T in prostate cancer have shown success, vaccine monotherapy has generally produced limited clinical benefit due to tumor heterogeneity, poor immune infiltration, and immunosuppressive tumor microenvironments. Multiple vaccine platforms have demonstrated safety and immunogenicity in prostate, renal cell, and urothelial cancers, but efficacy remains modest. Current strategies focus on multi-antigen targeting, improved antigen presentation, and combination therapies with immune checkpoint inhibitors, radiotherapy, and targeted agents to enhance antitumor activity. Advances in personalized vaccine design and delivery systems are driving progress, though challenges such as manufacturing complexity, cost, and biomarker development remain. Ongoing translational and clinical research will be critical to improving the effectiveness of vaccine-based immunotherapy in GU malignancies. Full article

Persistent challenges in cervical cancer (CC) control highlight the need for stage-specific cost estimates to refine prevention strategies. Structural integration of National Health Insurance (NHI) administrative claims, the Taiwan Cancer Registry (TCR), and the National Cause of Death Registry (NCDR) provided the empirical basis for this population-based research. The final analytical sample encompassed 6055 women with cervical intraepithelial neoplasia (CIN) identified in 2016 as well as 9318 patients diagnosed with stage I to IV invasive CC during the 2008 to 2015 period. Reimbursed direct medical costs were estimated for CIN within 6 months after diagnosis and for CC over 5 years after diagnosis. Across CIN grades, no consistent cost gradient was observed, although inpatient utilization was highest in CIN3. Among women with CC, healthcare utilization and expenditures were concentrated in the first year after diagnosis, accounting for 52–65% of the total 5-year costs. After age adjustment, the mean first-year costs increased from NT$256,095 (US$8413) in stage I to NT$474,724 (US$15,595) in stage IV, while 5-year survival declined from 85.3% to 19.5%. These findings show that cervical disease imposes substantial direct medical costs on Taiwan’s healthcare system and provide updated evidence to inform human papillomavirus (HPV) vaccination and CC screening policy. Full article

Messenger RNA (mRNA) therapeutics are redefining treatment approaches in vaccines, cancer immunotherapy, protein replacement, and gene editing. Lipid nanoparticles have enabled early clinical successes, but they can be limited by liver-dominant biodistribution, long-term storage stability, and systemic tolerability. Polymeric delivery systems offer a versatile alternative, with tunable physicochemical properties enabling precise control over mRNA complexation, protection, release, and targeting. This review examines recent progress across polyethyleneimine derivatives, poly(β-amino ester)s, poly(amino acid)s, polyesters, dendrimers, charge-altering releasable transporters, and lipid-polymer hybrids. We highlight strategies such as structural modification, stimuli-responsive designs, and high-throughput polymer screening that enhance stability, reduce cytotoxicity, and enable organ- or cell-specific delivery. Addressing challenges in immunogenicity, biodistribution, and manufacturing scalability will be pivotal to translating these innovations into safe and effective mRNA therapeutics. Full article

Leishmaniasis causes skin ulcers to complex visceral involvement, and available treatment options for humans are highly toxic and have prolonged application schemes. So far, there are no licensed vaccines for humans, so it is necessary to develop a strategy that can prevent the development of the disease. A cellular immune response of a CD4⁺ Th1 profile is essential to eliminate intracellular Leishmania amastigotes; therefore, the identification of sequences that bind to HLA class II pockets could induce a protective immune response. This study aimed to identify CD4⁺ T epitopes from immunogenic Leishmania proteins. First, three prediction tools were used to compare 15-mer sequences throughout the complete protein sequence against 25 HLA-DR alleles using NH, SMT, CPA, CPB, and CPC proteins. Six peptides were identified as strong HLA-DR binders using the three bioinformatic prediction tools. After alignment, molecular docking analysis, and molecular dynamics, the stability and affinity of the peptide–DR4 complex were confirmed for three sequences. This bioinformatics strategy allowed a sequential screening from 1857 to three promising candidates, namely, SMT_133-148, CPA_39-54, and CPA_301-316, which increases the probability of being natural Leishmania spp. CD4⁺ T cell epitopes in humans. Full article

Objective: To identify demographic, clinical, and behavioural determinants of COVID-19 vaccination and antiviral uptake in Australia using the Capability, Opportunity, Motivation-Behaviour (COM-B) framework with psychometric validation and LASSO-enhanced variable selection. Methods: Cross-sectional analysis of the 2024 KAB BREATHE survey (n = 5177) of Australian adults, intentionally enriched for risk-stacked (more than 1 chronic condition). Primary outcomes included 2023/2024 COVID-19 booster receipt, future vaccine intentions, vaccine/antiviral beliefs and antiviral uptake. Predictors included demographics, chronic conditions, and domain-specific leave-one-out (LOO) COM-B scores standardised to mean = 0, SD = 1. COM-B domains were assessed using Cronbach’s alpha. Univariate and multivariable logistic regression models were complemented by LASSO penalised logistic regression with 10-fold cross-validation. Results: Among 5177 Australian adults, the mean age was 51.5 years (SD 16.5), 61.4% (3179/5177) were female, and 70.3% (3638/5177) were classified as risk-stacked. Booster uptake declined sharply from 50.8% (2023) to 19.1% (2024). Cronbach’s alpha showed poor internal consistency for Capability (α = 0.006) and Opportunity (α = −0.383) but was acceptable for full Motivation (α = 0.78). In adjusted models, age (aOR 1.02–1.03 per year), medically associated risk factors (aOR 1.66–3.51), and tertiary education (aOR 1.34–1.79) consistently predicted higher uptake and intention. Renting (aOR 0.59–0.78) and current employment (likely inversely associated with age) (aOR 0.73–0.83) were associated with lower uptake across all vaccine outcomes. Adding LOO COM-B scores substantially improved model fit (e.g., 2024 booster AUC 0.73→0.83); Motivation per SD was the strongest predictor (aOR 2.44–4.94 for vaccine outcomes, 1.52–2.49 for antivirals). LASSO models achieved CV-AUCs of 0.78–0.87. Among COVID-positive respondents (n = 2576), only 15.2% received antiviral treatment. Conclusions: Age, clinical risk, and socioeconomic factors, particularly housing tenure and employment status, are key drivers of COVID-19 preventive behaviours (either positively or negatively). The COM-B framework, when corrected for circular prediction and validated via Cronbach’s alpha and LASSO, provides substantial explanatory value. Targeted interventions should address structural barriers faced by renters and younger, employed individuals while leveraging high motivation among older adults and clinically vulnerable groups. Implications for Public Health: These findings support a shift from knowledge-based campaigns towards equity-focused, multi-level public health strategies that address structural barriers to COVID-19 vaccination and antiviral access in Australia. Full article

The hepatitis B (HBV), C (HCV), and D (HDV) viruses remain a major public health burden. Occult HBV infection (OBI) represents a hidden reservoir with clinical and epidemiological significance, yet its prevalence in Northwest Russia is unknown. We aimed to comprehensively assess the serological and molecular epidemiology of HBV, HCV, and HDV in St. Petersburg and the Leningrad region. Methods. In this cross-sectional study, 6773 apparently healthy volunteers were enrolled. Plasma samples were tested for hepatitis B surface antigen (HBsAg), antibodies to HBV core antigen (anti-HBc), antibodies to HBsAg (anti-HBs), antibodies to HCV (anti-HCV), and antibodies to HDV (anti-HDV) by ELISA. All anti-HCV- and anti-HDV-positive samples were tested for HCV RNA and HDV RNA by real-time PCR. All samples were tested for HBV DNA using a highly sensitive in-house nested real-time PCR assay (detection limit: 5 IU/mL). All “HBV DNA-positive, HBsAg-negative” cases confirmed by two independent extractions were classified as OBI. Vaccination status, self-reported history, and iatrogenic interventions were recorded. Results. Overall seroprevalence values were: HBsAg 1.7%; anti-HBc 11.3%; anti-HBs 43.0%; anti-HCV 1.9%; and anti-HDV 0.6%. Anti-HBc increased sharply with age (3.1% in children to 26.4% in the elderly, p < 0.0001), while anti-HBs declined (69.9% to 29.8%, p < 0.0001). HBV DNA was detected in 118 participants (1.7%). Of these, only 73 individuals (1.1%) were HBsAg-positive, while the remaining 45 participants (0.7%) had undetectable HBsAg, meeting the criteria for OBI. OBI was detected across all age groups, including children. Serological profiling of OBI cases revealed that 57.8% lacked both anti-HBc and anti-HBs, 35.6% had isolated anti-HBs, 2.2% had isolated anti-HBc, and 4.4% had both antibodies. HCV RNA was detected in 15.0% of anti-HCV-positive individuals (all adults). No HDV RNA was detected. Self-reported history underestimated true infection rates: 1.4% of those denying HBV infection were HBsAg-positive and 10.6% were anti-HBc-positive. Among those denying HCV infection, 1.4% were anti-HCV-positive. Vaccination coverage was 70.8%, declining from 90.9% in children to 39.0% in the elderly (p < 0.0001). Among vaccinated individuals, 48.0% lacked protective anti-HBs (<10.0 mIU/mL). Conclusions. This comprehensive serological and molecular study in Northwest Russia is the first to combine population-level serology with molecular detection of HBV, HCV, and HDV, including OBI in this region, and reveals that OBI accounts for a substantial proportion (38%) of all active HBV infections and is strongly associated with a history of iatrogenic interventions. The presence of OBI across all age groups, including children, shows that HBsAg screening alone substantially underestimates the true HBV burden. High rates of unrecognized infection and waning vaccine-induced immunity, highlight critical gaps in current surveillance. These findings provide an evidence-based rationale for integrating molecular testing into screening algorithms and for considering booster vaccination strategies to achieve viral hepatitis elimination goals. Full article

:Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), is an acute, febrile, and highly contagious disease that has led to significant economic losses in the global swine industry. Although the attenuated lapinized CSF vaccine (C-strain) has effectively controlled CSF outbreaks in China since the 1950s, it remains challenging to serologically differentiate infected from vaccinated animals (DIVA). Currently, the application of E2 subunit vaccines allows for DIVA by detecting antibodies against the E^rns protein. Therefore, this study aimed to develop a blocking ELISA for CSFV E^rns antibody detection using porcine monoclonal antibodies (mAbs) derived from single B cell technology. Peripheral blood mononuclear cells (PBMCs) were isolated from immunized pigs, and single CD21⁺IgM⁻E^rns-His tag⁺ B cells were sorted via flow cytometry. Using one-step PCR, full-length genes of porcine IgG heavy and light chains were amplified separately, yielding 11 porcine mAbs against the CSFV E^rns protein. Among these, three mAbs (E0S3, E0S5, and E0S10) exhibited broad reactivity, while two (E0S1, E0S4) showed no cross-reaction with bovine viral diarrhea virus (BVDV). Using mAb E0S4 as the blocking antibody, a blocking ELISA was established and optimized. The assay demonstrated a detection limit of 1:128, no cross-reactivity with other swine viruses or BVDV, and intra- and inter-assay coefficients of variation below 10%. ROC curve analysis determined an optimal cut-off value of 48.4%, with high sensitivity and specificity. In conclusion, the developed blocking ELISA provides a reliable tool for high-throughput serological surveillance, facilitating the DIVA strategy and contributing to CSF eradication programs. Full article

Background: Short-form video platforms have become important channels for vaccine science communication, yet whether professionally produced vaccine content aligns with audience demand remains underexplored. Methods: We conducted a cross-sectional quantitative content analysis of 3752 publicly available vaccine-related videos retrieved from three major Chinese short-form video platforms between 21 November and 13 December 2024. A coding framework based on the Health Belief Model (HBM) and the World Health Organization (WHO) Behavioral and Social Drivers (BeSD) framework was used to identify key content themes. Multivariate Bayesian negative binomial regression and demand–avoidance analysis were used to examine engagement patterns and supply–demand alignment across account types. Results: Individual users produced the majority of videos (53.17%), whereas medical professionals received the highest level of engagement. Engagement was positively associated with themes related to disease severity (β ≈ 0.19–0.25) and side effects and management (β ≈ 0.31–0.67), but negatively associated with vaccine effectiveness (β ≈ −0.28 to −0.14) and vaccination precautions (β ≈ −0.28 to −0.27). Professional sources showed broader thematic coverage but also the greatest supply–demand mismatch, with mismatch indices of 0.377 for medical institution official media and 0.304 for medical professionals, primarily driven by overrepresentation of themes associated with audience avoidance. Conclusions: Significant structural mismatch exists between professionally produced vaccine content and audience engagement-based demand on short-form video platforms. Optimizing vaccine communication may require prioritizing audience-concerned risk-related information and dynamically adjusting content strategies based on engagement feedback to enhance the effectiveness of vaccine education. Full article

The concurrent circulation of SARS-CoV-2 and influenza presents a complex immunological landscape. While biological evidence suggests that prior or current infection with one virus can alter susceptibility to the other, conventional epidemiological models often obscure these effects by aggregating co-infected populations into a single compartment. This structural simplification limits our ability to quantify how infection history shapes population-level transmission dynamics. We developed a stratified, deterministic co-infection model that explicitly distinguishes between single, concurrent, and sequential infections by accounting for sequence-dependent heterogeneity in susceptibility and transmissibility. Our primary innovation is a transmission source–pathway decomposition framework that mathematically attributes the rate of new infections to its specific transmission source (i.e., which infectious subpopulation is generating the transmission: the singly-infected, co-infected, or sequentially-infected class) and transmission pathway (i.e., which susceptibility class is receiving new infections: fully susceptible individuals, or those with prior immunity, or those with active co-infection). This framework accounts for altered susceptibility and transmissibility dependent on infection history. Our model-based analysis reveals a profound, sequence-driven asymmetry in transmission. In a baseline co-epidemic scenario, COVID-19 is predominantly driven by a sequential source: individuals who contracted COVID-19 after recovering from influenza are estimated to account for approximately 73% of new COVID-19 cases and approximately 76% of the disease burden, as predicted by our model. Conversely, influenza transmission remains driven by singly infected individuals (approximately 96% of new influenza cases inferred using our model). This sequence-driven asymmetry was robust to changes in model structure (especially, the inclusion of an influenza latent period in a sensitivity analysis) and across scenarios of varying relative transmissibility for the two viruses. Interventions exhibit pathway-specific effects: COVID-19 vaccination, for instance, disproportionately disrupts this dominant sequential transmission engine by protecting the most immunologically vulnerable hosts. Our model-based findings suggest that infection history may be a primary driver of co-epidemic dynamics. Our framework reveals a plausible, asymmetric interaction where an initial influenza wave can fundamentally reshape the transmission landscape for COVID-19, and demonstrates how a prior COVID-19 wave may fuel subsequent influenza transmission under specific temporal conditions. These findings generate the testable hypothesis that cross-viral susceptibility is a key control point and underscore the importance of pathway-aware intervention strategies that account for infection history. Full article

Background/Objectives: Vaccine clinical trials face high costs, long timelines, and variable progression rates, yet systematic evidence linking trial design features to progression outcomes remains limited. This study aimed to identify trial design features associated with vaccine trial progression and to explore robust design configurations using machine learning approaches. Methods: We analyzed 1618 vaccine trials registered from 2012 to 2022. Progression was defined as phase advancement (phase I/II) or regulatory authorization (phase III). Logistic regression assessed associations with progression. Random forest classifiers with cross-validation were used to estimate predicted progression probabilities based on combinations of design features. Monte Carlo simulations compared model-identified robust configurations with randomly generated configurations. Results: Among 1618 trials, 579 achieved phase progressions, corresponding to an overall observed progression rate of 35.8%. Larger sample size, preventive vaccine purpose, COVID-19 indication, and enrollment across all age groups were consistently associated with higher observed odds of progression in both univariable and multivariable logistic regression analyses. In machine learning analyses, the pooled mean predicted progression probability of model-identified robust configurations was 48.93%, compared with 39.44% for historically observed design configurations, corresponding to a relative increase of 24.1%. Simulations further showed a lower projected cumulative development duration (106.87 vs. 128.25 months; −16.7%) and reduced projected cost (USD 100.67M vs. USD 108.33M; −7.1%) for robust configurations compared with historical strategies. Conclusions: This study provides a data-driven framework for characterizing historical vaccine trial design patterns. By integrating machine learning with observational registry data, it supports hypothesis generation and descriptive benchmarking of design features that may inform the design of future prospective or causal investigations. Full article