Search Results (5,295)

Rabies remains a significant global public health concern, causing an estimated 59,000–69,000 human fatalities annually. Despite being entirely preventable through vaccination, rabies continues to impose substantial economic burdens worldwide. This study presents a scoping review of the economic research on rabies to determine overlaps and gaps in knowledge and inform future research strategies. We selected 150 studies (1973–2024) to analyze. The review categorizes the literature based on geographic distribution, species focus, and type of study. Findings indicate that economic studies are disproportionately concentrated in developed countries, such as the United States and parts of Europe, where rabies risk is low, while high-risk regions, particularly in Africa and Asia, remain underrepresented. Most studies focus on dog-mediated rabies, reflecting its dominant role in human transmission, while fewer studies assess the economic impacts of wildlife and livestock-mediated rabies. Case studies and modeling approaches dominate the literature, whereas cost–benefit and cost–effectiveness analyses—critical for informing resource allocation—are limited. The review highlights the need for more economic evaluations in rabies-endemic regions, expanded research on non-dog reservoirs, and broader use of economic methods. Addressing these gaps will be crucial for optimizing rabies control and supporting global initiatives to eliminate dog-mediated rabies by 2030. Full article

Background: Cervical cancer poses a threat to the health of women globally. Adolescent girls are the primary target population for HPV vaccination, and guardians’ attitude towards the HPV vaccine plays a significant role in determining the vaccination status among adolescent girls. Objectives: This study aimed to explore the factors influencing guardians’ HPV vaccine acceptance for their girls and provide clues for the development of health intervention strategies. Methods: Combining the health belief model as a theoretical framework, a questionnaire-based survey was conducted. A total of 2157 adolescent girls and their guardians were recruited. The multivariable logistic model was applied to explore associated factors. Results: The guardians had a high HPV vaccine acceptance rate (86.7%) for their girls, and they demonstrated a relatively good level of awareness regarding HPV and HPV vaccines. Factors influencing guardians’ HPV vaccine acceptance for girls included guardians’ education background (OR = 0.57, 95%CI = 0.37–0.87), family income (OR = 1.94, 95%CI = 1.14–3.32), risk of HPV infection (OR = 3.15, 95%CI = 1.40–7.10) or importance of the HPV vaccine for their girls (OR = 6.70, 95%CI = 1.61–27.83), vaccination status surrounding them (OR = 2.03, 95%CI = 1.41–2.92), awareness of negative information about HPV vaccines (OR = 0.59, 95%CI = 0.43–0.82), and recommendations from medical staff (OR = 2.32, 95%CI = 1.65–3.25). Also, guardians preferred to get digital information on vaccines via government or CDC platforms, WeChat platforms, and medical knowledge platforms. Conclusions: Though HPV vaccine willingness was high among Chinese guardians, they preferred to vaccinate their daughters at the age of 17–18 years, later than WHO’s recommended optimal age period (9–14 years old), coupled with safety concerns. Future work should be conducted based on these findings to explore digital intervention effects on girls’ vaccination compliance. Full article

Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8⁺ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article

Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 Å resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue β4–β5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand–DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Full article

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this context, cancer vaccines have emerged as a promising immunotherapeutic strategy. By activating the host immune system to eliminate tumor cells, cancer vaccines offer high specificity, low toxicity, and the potential to induce long-lasting immune memory. These advantages have positioned them as a focal point in cancer immunotherapy research. This paper provides a comprehensive overview of recent clinical advances in lung cancer vaccines, discusses the major challenges impeding their clinical application, and explores potential strategies to overcome these barriers. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-stranded positive-sense RNA virus, poses a significant threat to global swine production. Despite the availability of modified live virus and inactivated vaccines, their limited efficacy and safety concerns highlight the urgent need for novel antiviral therapeutics. This study aimed to investigate the molecular mechanisms by which lycopene inhibits PRRSV replication. Initial assessments confirmed that lycopene did not adversely affect cellular viability, cell cycle progression, or apoptosis. Using fluorescence microscopy, flow cytometry, immunoblotting, quantitative real-time PCR (qRT-PCR), and viral titration assays, lycopene was shown to exhibit potent antiviral activity against PRRSV. Mechanistic studies revealed that lycopene suppresses reactive oxygen species (ROS) production, which is critical for PRRSV proliferation. Additionally, lycopene attenuated PRRSV-induced inflammatory responses, as demonstrated by immunoblotting, ELISA, and qRT-PCR assays. These findings suggest that lycopene inhibits PRRSV replication by modulating ROS levels and mitigating inflammation, offering a promising avenue for the development of antiviral therapeutics. This study provides new insights and strategies for combating PRRSV infections, emphasizing the potential of lycopene as a safe and effective antiviral agent. Full article

The repeated occurrence of SARS-CoV-2 variants, largely driven by virus–host interactions, was and will remain a public health concern. Spike protein mutations shaped viral infectivity, transmissibility, and immune escape. From February 2022 to April 2024, a local genomic surveillance program in Verona, Italy, was conducted on 1333 SARS-CoV-2-positive nasopharyngeal swabs via next generation full-length genome sequencing. Spike protein mutations were classified based on their prevalence over time. Mutations were grouped into five categories: fixed, emerging, fading, transient, and divergent. Notably, some divergent mutations displayed a “Lazarus effect,” disappearing and later reappearing in new lineages, indicating potential adaptive advantages in specific genomic contexts. This two-year surveillance study highlights the dynamic nature of spike protein mutations and their role in SARS-CoV-2 evolution. The findings underscore the need for ongoing mutation-focused genomic monitoring to detect early signals of variant emergence, especially among mutations previously considered disadvantageous. Such efforts are critical for driving public health responses and guiding future vaccine and therapeutic strategies. Full article

Despite growing global momentum to reduce the number of children who never received a dose of any vaccine, i.e., zero-dose (ZD) children, persistent geographic and social inequities continue to undermine progress toward universal immunization coverage. In Madagascar, where routine vaccination coverage remains below 50% in most regions, the non-governmental organization Doctors for Madagascar and public sector partners are implementing the SOAMEVA program: a targeted community-based initiative to identify and reach ZD children in sixteen underserved districts in the country’s south. This paper outlines the equity-sensitive evaluation design developed to assess the implementation and impact of SOAMEVA. It presents a forward-looking evaluation framework that integrates both quantitative program monitoring and qualitative community insights. By focusing at the fokontany level—the smallest administrative unit in Madagascar—the evaluation captures small-scale variation in ZD prevalence and program reach, allowing for a detailed analysis of disparities often masked in aggregated data. Importantly, the evaluation includes structured feedback loops with community health workers and caregivers, surfacing local knowledge on barriers to immunization access and program adoption. It also tracks real-time adaptations to implementation strategy across diverse contexts, offering insight into how routine immunization programs can be made more responsive, sustainable, and equitable. We propose eight design principles for conducting equity-sensitive evaluation of immunization programs in similar fragile settings. Full article

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article

Porcine circovirus type 2 (PCV2) is a globally prevalent swine pathogen that induces immunosuppression, predisposing pigs to subclinical infections. In intensive farming systems, PCV2 persistently impairs growth performance and vaccine efficacy, leading to substantial economic losses in the swine industry. Emerging evidence suggests that certain viruses exploit Suppressor of Cytokine Signaling 3 (SOCS3), a key immune checkpoint protein, to subvert host innate immunity by suppressing cytokine signaling. While SOCS3 has been implicated in various viral infections, its regulatory role in PCV2 replication remains undefined. This study aims to elucidate the mechanisms underlying the interplay between SOCS3 and PCV2 during viral pathogenesis. Porcine SOCS3 was amplified using RT-PCR and stably overexpressed in PK-15 cells through lentiviral delivery. Bioinformatics analysis facilitated the design of three siRNA candidates targeting SOCS3. We systematically investigated the effects of SOCS3 overexpression and knockdown on PCV2 replication kinetics and host antiviral responses by quantifying the viral DNA load and the mRNA levels of cytokines. PCV2 infection upregulated SOCS3 expression at both transcriptional and translational levels in PK-15 cells. Functional studies revealed that SOCS3 overexpression markedly enhanced viral replication, whereas its knockdown suppressed viral proliferation. Intriguingly, SOCS3-mediated immune modulation exhibited a divergent regulation of antiviral cytokines: PCV2-infected SOCS3-overexpressing cells showed elevated IFN-β but suppressed TNF-α expressions, whereas SOCS3 silencing conversely downregulated IFN-β while amplifying TNF-α responses. This study unveils a dual role of SOCS3 during subclinical porcine circovirus type 2 (PCV2) infection: it functions as a host-derived pro-viral factor that facilitates viral replication while simultaneously reshaping the cytokine milieu to suppress overt inflammatory responses. These findings provide novel insights into the mechanisms underlying PCV2 immune evasion and persistence and establish a theoretical framework for the development of host-targeted control strategies. Although our results identify SOCS3 as a key host determinant of PCV2 persistence, the precise molecular pathways involved require rigorous experimental validation. Full article

Background: It is still challenging to develop effective vaccines against tumorigenic human gammaherpesviruses such as Epstein–Barr virus (EBV). A major obstacle is the lack of a small animal model that reproduces the natural infection course of human gammaherpesviruses to allow for proper assessment of vaccine efficacy. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of wild rodents and laboratory mice and therefore can be used as a surrogate for human gammaherpesviruses to evaluate vaccination strategies. Methods: In this study, two mRNA vaccine candidates were generated, one encoding a fusion protein of the MHV68 gH with the gL (gHgL-mRNA) and the other expressing the MHV68 gB protein (gB-mRNA). The immunogenicity and protective efficacy of the mRNA vaccine candidates were evaluated in a mouse model of MHV68 infection. Results: The gHgL-mRNA but not the gB-mRNA candidate vaccine was able to induce neutralizing antibodies in mice, whereas both vaccines could elicit antigen-specific T-cell responses. Following MHV68 intranasal inoculation, complete blocking of the establishment of viral latency was observed in some mice immunized with individual gHgL-mRNA or gB-mRNA vaccines. Notably, co-immunization with the two mRNA vaccines appeared to be more effective than individual vaccines, achieving sterile immunity in 50% of the vaccinated mice. Conclusions: This study demonstrates that immunization with mRNA platform-based subunit vaccines is indeed capable of preventing MHV68 latent infection, thus validating a safe and efficacious vaccination strategy that may be applicable to human gammaherpesviruses. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Furunculosis caused by Aeromonas salmonicida poses a significant challenge to the sustainable production of maraena whitefish (Coregonus maraena). This case report outlines a multi-year disease management strategy at a European whitefish facility with two production departments, each specialising in different life-cycle stages. Recurrent outbreaks of A. salmonicida necessitated the development of effective vaccination protocols. Herd-specific immersion vaccines failed to confer protection, while injectable formulations with plant-based adjuvants caused severe adverse reactions and mortality rates exceeding 30%. In contrast, the bivalent vaccine Alpha Ject 3000, containing inactivated A. salmonicida and Vibrio anguillarum with a mineral oil adjuvant, yielded high tolerability and durable protection in over one million whitefish. Post-vaccination mortality remained low (3.3%), aligning with industry benchmarks, and furunculosis-related losses were fully prevented in both departments. Transcriptomic profiling of immune-relevant tissues revealed distinct gene expression signatures depending on vaccine type and time post-vaccination. Both the herd-specific vaccine and Alpha Ject 3000 induced the expression of immunoglobulin and inflammatory markers in the spleen, contrasted by reduced immunoglobulin transcript levels in the gills and head kidney together with the downregulated expression of B-cell markers. These results demonstrate that an optimised injectable vaccination strategy can significantly improve health outcomes and disease resilience in maraena whitefish aquaculture. Full article

In today’s volatile supply chain environment, organizations require flexible and collaborative procurement strategies. Swap contracts, originally developed as financial instruments, have recently been adopted to address inventory imbalances—such as the 2021 COVID-19 vaccine swap between South Korea and Israel. Despite its increasing adoption in the real world, theoretical studies on swap-based procurement remain limited. This study proposes an integrated model that combines buyer-to-buyer swap agreements with long-term wholesale contracts under demand uncertainty. The model quantifies the expected swap quantity between parties and embeds it into the profit function to derive optimal order quantities. Numerical experiments are conducted to compare the performance of the proposed strategy with that of a baseline wholesale contract. Sensitivity analyses are performed on key parameters, including demand asymmetry and swap prices. The numerical analysis indicates that the swap-integrated procurement strategy consistently outperforms procurement based on long-term wholesale contracts. Moreover, the results reveal that under the swap-integrated strategy, the optimal order quantity must be adjusted—either increased or decreased—depending on the demand scale of the counterpart and the specified swap price, deviating from the optimal quantity under traditional long-term contracts. These findings highlight the potential of swap-integrated procurement strategies as practical coordination mechanisms across both private and public sectors, offering strategic value in contexts such as vaccine distribution, fresh produce, and other critical products. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy. Full article