Search Results (10,873)

Since MDCK cells are inherently tumorigenic, their safety in vaccine production has long been a concern; thus, establishing a screening method for low-tumorigenic cells is of great significance for influenza vaccine development. This study successfully obtained a low-tumorigenic MDCK cell line through monoclonal screening and systematically evaluated its potential as a cellular substrate for influenza vaccines using male nude mice (BALB/c nu/nu, 4–7 weeks old) for tumorigenicity assessment. Comprehensive analysis of the biological characteristics of the screened cells—including growth curves and transcriptomic features—showed that the cell line exhibits stable growth and consistent traits. Transcriptomic comparison was performed between two defined biological states: parental MDCK cells (SQ group) and the low-tumorigenic clone MDCK-20B9 (SH group). Transcriptomic analysis revealed good dispersion among samples and an overall consistent gene expression distribution. Differential expression analysis identified a total of 2198 differentially expressed genes, including 902 upregulated and 1296 downregulated genes. GO functional enrichment analysis indicated that these genes are mainly involved in biological processes such as acute-phase response, retinol metabolism, mitotic chromosome condensation, and cell migration; are enriched in cellular components such as kinetochores and the extracellular matrix; and are associated with molecular functions including calcium ion binding and the Wnt signaling pathway. KEGG pathway analysis further revealed that the differentially expressed genes are significantly enriched in key pathways such as cancer pathways, cell cycle, and cell adhesion molecules. The expression trends of five key differentially expressed genes were validated by RT-qPCR. In summary, this study successfully screened a stable and consistent low-tumorigenic MDCK cell line, providing a theoretical basis and practical foundation for its use as a cellular substrate in influenza vaccine development. Full article

Brucellosis is an important zoonotic disease caused by Brucella spp., posing significant impacts on animal health, livestock production, and public health. Infected dairy animals can shed the pathogen in milk, making milk a noninvasive and readily accessible sample for disease surveillance. Therefore, detection of Brucella in milk can be used for monitoring brucellosis in dairy herds. In this study, polyclonal antibodies were produced by immunizing camels with lipopolysaccharide (LPS) derived from Brucella abortus vaccine strain 19 (A19). These antibodies were subsequently conjugated to magnetic beads to develop immunomagnetic beads (IMBs). The IMBs were combined with a sandwich ELISA for the enrichment and detection of Brucella in milk samples. The IMB-sELISA showed a limit of detection (LOD) of 1 × 10⁴ CFU/mL. The method reduced matrix interference and showed satisfactory analytical performance. This approach can be applied for on-farm sample screening and herd-level surveillance to support the diagnosis and control of brucellosis in dairy animals. Full article

Background/Objectives: Vaccination is a critical public health intervention, yet its global implementation is hindered by high production costs and cold-chain requirements. This review aims to evaluate plant-based systems as sustainable, cost-efficient alternatives for vaccine production. Methods: A comprehensive literature search was conducted across major databases (PubMed, Scopus, Web of Science). The peer-reviewed references were critically assessed, focusing on molecular expression strategies, phytochemical immunomodulators, and plant-mediated oral delivery. Results: Plant and microalgae systems effectively support nuclear, chloroplast, and transient expression of diverse antigens. Furthermore, specific plant-derived compounds were found to act as potent adjuvants and immunostimulants, enhancing the immunogenicity of vaccine formulations. Edible plant tissues also provide a viable platform for oral delivery, reducing the need for extensive purification and refrigerated logistics. Conclusions: Integrating recombinant expression technologies with bioactive plant metabolites offers a flexible and scalable foundation for next-generation vaccines. These biological platforms show promise for addressing some immunization challenges, particularly in low-resource settings. Full article

Background: Varicella burden is closely linked to national socioeconomic development, yet systematic analyses of its non-linear relationship with the Socio-demographic Index (SDI) are lacking. This study aims to elucidate this relationship and inform equitable, context-specific strategies. Methods: Based on data from the Global Burden of Diseases 2021 study, we analyzed global trends (1990–2021) in the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of varicella. Joinpoint regression was used to identify trend transition points, and an autoregressive integrated moving average (ARIMA) model was applied to forecast the disease burden through 2035. Analyses were conducted, and countries and territories were stratified into five SDI groups: high (SDI > 0.81), high–middle (0.70–0.81), middle (0.61–0.69), low–middle (0.46–0.60), and low (SDI < 0.46). These approaches aimed to systematically elucidate the socioeconomic gradient of the varicella burden and to specifically investigate its potential non-linear relationship with SDI. Results: From 1990 to 2021, global age-standardized mortality and DALYs declined by −45.71% (95% UI: −48.32% to −42.95%) and −36.15% (95% UI: −39.04% to −33.01%), respectively, while incidence and prevalence rates slightly increased. A significant U-shaped relationship emerged between burden and SDI, with rates highest in low- and high-SDI regions. The rise in high-SDI regions was driven by increasing incidence and prevalence from 1996 to 2015. Projections to 2035 indicate continued global decline but persistent disparities. Conclusions: The varicella burden follows a U-shaped socioeconomic gradient. Rising incidence in high-SDI regions highlights that economic development and routine pediatric vaccination alone are insufficient. Precision strategies tailored to SDI levels—closing adult immunity gaps in high-SDI, sustaining gains in middle-SDI, and expanding vaccine access in low-SDI regions—are essential. Full article

Background: The emergence of SARS-CoV-2 variants necessitates the development of effective adjuvants to enhance subunit vaccine immunogenicity. Safe adjuvants are essential to enhance the immunogenicity of SARS-CoV-2 receptor-binding domain (RBD) subunit vaccines. Traditional Chinese medicine polysaccharides are attractive candidates due to their immunomodulatory properties. Methods: Female BALB/c mice (6–8 weeks) were immunized on days 0, 7, and 21 with an RBD protein (20 μg) alone or formulated with Poria cocos polysaccharide fraction PCP-I or PCP-II (200 μg), Isatis indigotica polysaccharide, or aluminum adjuvant; PBS served as a control. RBD-specific total IgG and subclasses were quantified by ELISA on day 7 after the third immunization. Neutralizing antibody titers were measured by a pseudovirus assay on days 14, 28, and 56 after the first immunization. Splenic CD19⁺ B cells were analyzed by flow cytometry, and antigen-stimulated IFN-γ and IL-4 spot-forming cells were quantified by ELISpot. Results: PCP-II significantly increased RBD-specific total IgG and IgG1 compared with RBD alone and other formulations, whereas IgG2a and IgG2b remained unchanged. Both PCP-I and PCP-II increased neutralizing titers versus RBD alone, and PCP-II showed an earlier and sustained increase in neutralizing responses through day 56. PCP-II showed a non-significant increase in splenic CD19⁺ B cell frequency. PCP-I and PCP-II markedly increased IFN-γ-secreting splenocytes without increasing IL-4, indicating enhanced antigen-specific cellular responses. Conclusion: In this comparative evaluation of traditional Chinese medicine polysaccharide candidates in a SARS-CoV-2 RBD subunit vaccine model, PCP-II showed the most prominent adjuvant activity. PCP-II enhanced antigen-specific humoral immunogenicity, improved neutralizing antibody responses, and was associated with increased IFN-γ-related cellular responses, supporting its potential as a candidate polysaccharide adjuvant for protein subunit vaccines. Full article

Background: Porcine epidemic diarrhea virus (PEDV) remains a major threat to the global swine industry, highlighting the urgent need for safe and effective next-generation vaccines. mRNA vaccines have emerged as a promising platform due to their rapid development and favorable safety profile. Objectives: This study aimed to design and perform the preliminary evaluation of a PEDV multi-epitope mRNA vaccine using an immunoinformatics-guided strategy combined with experimental validation. Methods: Immunoinformatics tools were used to identify B-cell and cytotoxic T lymphocyte (CTL) epitopes from the PEDV spike (S), membrane (M), and nucleocapsid (N) proteins. Selected epitopes were assembled into a multi-epitope antigen (E). mRNA constructs encoding S1, S2, and antigen E were synthesized via in vitro transcription and encapsulated into lipid nanoparticles (LNPs). Expression was evaluated in HEK293T cells, and immunogenicity was assessed in mice measuring antigen-specific antibody responses and cytokine levels following immunization. Results: The mRNA constructs exhibited high structural integrity and efficient intracellular translation. The LNP formulations showed good physicochemical stability and delivery efficiency. Immunization with the antigen E mRNA-LNP formulation induced significantly higher PEDV-specific IgG levels compared with control groups. Elevated cytokine levels further indicated activation of both humoral and cellular immune responses. Conclusions: This study presents a feasible workflow for the development of a PEDV multi-epitope mRNA vaccine. The antigen E construct demonstrated favorable immunogenicity in a mouse model, supporting its potential as a promising construct for further investigation and optimization. Although further studies are required to validate antigen expression at the protein level and to further characterize immune mechanisms, these findings provide preliminary evidence supporting the feasibility of multi-epitope mRNA vaccines for PEDV prevention. Full article

Lipid nanoparticles (LNPs) have become the cornerstone of nucleic acid delivery platforms, particularly in RNA-based vaccines and therapeutics. However, the conventional methods of LNP production, which are primarily reliant on microfluidic mixing of aqueous and organic solvent phases, pose limitations in terms of mRNA stability, residual organic contamination, scalability, cost, and environmental impact. These limitations prompted a renewed search for non-conventional strategies with the promise of improving mRNA-LNP encapsulation approaches. These emerging approaches aim to address key bottlenecks, including mRNA hydrolysis-driven degradation, high production losses, and complex downstream purification. Moreover, the ability to decouple LNP synthesis from mRNA encapsulation could enable streamlined, modular manufacturing workflows and customizable payload delivery, including single- or multiple-mRNA payloads, thereby expanding the therapeutic scope of LNPs. This review offers an early insight into the design principles and scalability potential of emerging non-conventional LNP encapsulation approaches, including solvent-free and microfluidics-free methodologies, and pre-built LNP workflows. We also examine trends in emerging LNP encapsulation tools, including high-shear mixing, sonication, membrane contraction, and other approaches. Finally, we extrapolate the suitability of the methods for scale-up approaches and their economic implications based on the process information. Full article

Background: Photodynamic therapy (PDT) has emerged as a powerful minimally invasive modality for cancer treatment. However, its efficacy as a monotherapy is often limited by oxygen dependence and limited light penetration. Combining PDT with systemic anticancer drug therapies offers a promising strategy to achieve synergistic effects and overcome resistance. Objective: This review aims to provide a systematic analysis of the mechanisms and clinical potential of combining PDT with chemotherapy, targeted therapy, and immunotherapy, focusing on recent advancements and nanotechnology-based delivery systems. Methods: A comprehensive literature search was performed using PubMed and Scopus databases. The analysis focused on peer-reviewed studies published over the last 10 years addressing synergistic molecular pathways, co-delivery nanoplatforms, and clinical trial outcomes. Results: The combination of PDT with chemotherapy enhances drug accumulation via vascular photosensitization and can overcome multi-drug resistance. Integration with immunotherapy, particularly immune checkpoint inhibitors and tumor vaccines, triggers immunogenic cell death (ICD), leading to systemic antitumor responses. Nanotechnology provides a versatile platform for the targeted co-delivery of photosensitizers and pharmacological agents, significantly reducing systemic toxicity. Conclusions: Combined PDT–drug regimens demonstrate superior therapeutic efficacy compared to monotherapies. Future clinical translation requires the standardization of dosimetry and the development of multifunctional nanomedicines to enable personalized treatment protocols. Full article

Background/Objectives: Extraintestinal pathogenic Escherichia coli (ExPEC) is a major pathogen that causes septicemia, meningitis, and polyserositis in pigs. The increasing prevalence of antimicrobial resistance and the diverse serotypes of ExPEC highlight the urgent need for broadly protective vaccines. Methods and Results: In this study, an OmpC epitope vaccine based on the T4 phage display system was developed and evaluated. Two B-cell epitopes (OmpC-1 and OmpC-2) were identified by bioinformatic analysis and displayed on recombinant T4 phages. Immunization induced strong antigen-specific IgG responses, with the OmpC-1-T4 group showing significantly higher antibody titers than the OmpC protein group. In the O11 serotype PCN033 challenge model, survival rates reached 100% in the OmpC-1-T4 group, 60% in the OmpC-2-T4 group, and approximately 80% in the OmpC protein group. In the O18 serotype 2103 challenge model, both recombinant phage groups had survival rates of approximately 60%, whereas all the mice in the OmpC protein group died within three days. OmpC-1-T4 immunization also significantly reduced bacterial loads in lung and brain tissues after PCN033 infection and decreased TNF-α and IL-6 expression in lung tissues, accompanied by reduced inflammatory infiltration and tissue damage. Conclusions: Overall, the T4 phage-displayed OmpC epitope vaccine induced strong humoral immunity and provided protection against different ExPEC serotypes. Among the candidates, OmpC-1-T4 showed superior immune protection, bacterial clearance, and inflammation control, supporting its potential as a vaccine candidate against porcine ExPEC infection. Full article

Background: In the Republic of Korea, a bivalent foot-and-mouth disease (FMD) vaccine covering serotypes O and A is administered to livestock, while antigens for the other serotypes are stockpiled in overseas antigen banks. To achieve self-reliance in FMD vaccine production, various vaccine strains have been developed using in-house technology. Although SAT 3 has historically been confined largely to Africa, preparedness against this serotype remains necessary, as the possibility of its introduction into Korea cannot be completely excluded. Methods: In this regard, we evaluated the commercial potential of the SAT 3 ZIM-R vaccine strain by assessing antigen productivity, scalability, inactivation kinetics, and immunogenicity. Results: Supplementation with 3 mM Ca²⁺ markedly increased antigen yield compared with that obtained in the absence of calcium. Further optimization showed that antigen yield was highest at pH 8.0–8.5. During scale-up, antigen yield was maintained at 9.2–9.8 μg/mL in flask cultures and remained high at approximately 7.8 μg/mL in a bioreactor, demonstrating robust scalability. Treatment with 2 mM binary ethylenimine at 26 °C achieved complete inactivation within 24 h. Vaccines formulated with the SAT 3 ZIM-R antigen produced either in flasks or in a bioreactor induced comparable neutralizing antibody responses in pigs following both the primary and booster immunizations. Conclusions: Collectively, these findings indicate that SAT 3 ZIM-R is a promising vaccine candidate for large-scale vaccine antigen production and the future establishment of a domestic FMD antigen bank in Korea. Full article

Measles remains a major global public health challenge as declining vaccination coverage fuels outbreaks worldwide. Although pneumonia is the most recognized respiratory complication, spontaneous air leak syndrome—including pneumomediastinum, subcutaneous emphysema, and pneumoperitoneum—is rarely documented. We report the case of a 9-year-old previously healthy girl with no documented measles–rubella vaccination who presented with fever, maculopapular exanthem, Koplik spots, and persistent cough. Measles was confirmed by both immunoglobulin M enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction. She developed sudden cervicothoracic swelling and chest pain. Chest radiography revealed pneumomediastinum and subcutaneous emphysema; computed tomography confirmed extensive air leak including pneumoperitoneum. Flexible bronchoscopy and upper gastrointestinal endoscopy excluded structural airway and esophageal injury. Laboratory evaluation revealed elevated hepatic transaminases, gamma-glutamyl transferase, lactate dehydrogenase, and D-dimer. Conservative management with high-flow supplemental oxygen and clinical surveillance led to progressive resolution. The patient was discharged on hospital day three, asymptomatic and breathing room air. This case highlights the spectrum of air leak complications in measles and supports conservative management in hemodynamically stable pediatric patients when structural injury has been excluded. Full article

Background: There is a high burden of influenza among individuals aged 50–64 years, with the highest rates of influenza infections other than children. The MF59-adjuvanted influenza vaccine (adjuvanted trivalent influenza vaccine [aTIV]/adjuvanted quadrivalent influenza vaccine [aQIV]) is designed to enhance response to vaccination among older adults. Among those aged ≥65 years, adjuvanted vaccine (aTIV/aQIV) has shown to be 14% more effective than standard (TIV/QIV) vaccines. This modeling study aimed to estimate the potential public health impact of aTIV/aQIV over standard influenza vaccines (TIV/QIV) among individuals aged 50–64 years over five influenza seasons. Methods: A static compartmental model was developed based on a Centers for Disease Control and Prevention model. Model inputs included vaccine effectiveness, vaccine coverage, population counts and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses explored the influence of uncertainties in model input on the results. Results: Across the influenza seasons evaluated, on average each 5% increase in the relative vaccine effectiveness (rVE) of aTIV/aQIV vs. QIV prevented an additional 172,738 symptomatic illnesses, 74,277 outpatient visits, 1832 hospitalizations, 343 ICU admissions, and 105 deaths. This corresponds to an average seasonal incremental burden averted of 15.2%, with a range of 5.9% to 37.2%. Deterministic sensitivity analyses revealed the greatest variability was tied to rVE and burden estimates. Probabilistic sensitivity analyses results were normally distributed. Conclusions: Individuals aged 50–64 years could benefit from use of aTIV/aQIV over TIV/QIV, with an average increase in the number of influenza outcomes prevented of 15.2% per 5% improvement in vaccine effectiveness. Full article

Plant extracts are widely used as natural pesticides, cosmetic ingredients, and in pharmaceutical applications. However, their poor water solubility and stability limit their usability. Lipid nanoparticles (LNPs) offer an effective encapsulation strategy to overcome these challenges. This study demonstrates the encapsulation of three representative substances from these industries: quercetin as a pesticide, irones as a cosmetic ingredient, and nucleic acids for pharmaceutical use. Ultrasonic treatment was used for the encapsulation of quercetin and irones, and a concept for continuous encapsulation in a plug flow reactor was proposed for process intensification. Inline multi-angle light scattering and dynamic light scattering measurements proved effective for real-time monitoring and enabled the replacement of traditional batch measurements. In the pharmaceutical area, mRNA-based therapies require LNP encapsulation to prevent nucleic acid degradation. Plant-based β-sitosterol was used as an alternative helper lipid to cholesterol, resulting in an average particle diameter of 72 nm and an encapsulation efficiency of 91%, comparable to commercial formulations such as the Comirnaty vaccine. Furthermore, a novel process model based on population balances was developed to simulate the entire manufacturing process, from rapid mixing in a T-mixer to particle stabilization via buffer exchange during diafiltration. By applying a quantitative and distinctive model validation workflow, the model was shown to be as accurate and precise as the experimental data, enabling its use as a digital twin for autonomous continuous operation. In summary, this study contributes to reducing the facility footprint and cost of goods through the implementation of continuous processing and model-based control. This approach improves productivity by 20% and reduces process time by a factor of two. Full article

Melanoma is a heterogeneous, complex and aggressive disease that, despite recent advances in molecular-targeted drugs and molecular and genetic analysis, represents approximately 65% of skin cancer deaths, and unfortunately survival dramatically decreases in melanoma stages III/IV. In young people there is an increased incidence of developing melanoma; hence new therapeutic strategies must be urgently investigated. Peptidergic systems play a crucial role in these strategies to fight melanoma. The scope of this review is to show the enormous potential of targeting peptidergic systems alone or in combination therapy with standard therapeutic strategies currently used in clinical practice to treat melanoma. In this sense, key points such as peptidergic systems and anti-melanoma treatments, oncogenic/anti-melanoma peptides, peptide receptors, peptidergic systems, melanoma risk and immune system relationships, clinical relevance, peptidergic systems and delivery strategies in melanoma will be discussed. Peptides exert oncogenic, anti-melanoma and dual oncogenic and anti-melanoma effects in melanoma, showing a high functional complexity in regulating melanoma development. A plethora of anti-melanoma strategies have been developed or repurposed for potential clinical applications, including peptide/peptide receptor antibodies, peptide receptor antagonists or agonists, enzyme inhibitors, CAR-macrophages, microRNAs and vaccines. Strategies for peptide delivery and protection from enzymatic degradation have also been developed. Some of the previous anti-melanoma strategies are based on the expression/overexpression of peptide receptors in melanoma cells which is crucial for diagnosis, melanoma risk and progression and metastasis development and for the application of more specific and safer anti-melanoma strategies. A meticulous and in-depth study of the peptidergic systems may help to understand how peptidergic systems regulate melanoma progression and shed light on possible therapeutic applications that can be applied in clinical practice. This review shows the enormous potential of targeting peptidergic systems alone or in combination therapy with standard therapeutic strategies currently used in clinical practice to treat melanoma. The benefits to be gained from these studies will be enormous because the peptidergic systems are promising antitumor targets in melanoma, based on the numerous anti-melanoma strategies that have been developed until now. Full article

Introduction: Placental malaria increases the risk of adverse birth outcomes. Current preventive measures are undermined by poor coverage, growing resistance to chemo-preventive and therapeutic drugs, and vector eliminating insecticides. Candidate placental malaria (PM) vaccines (PAMVAC and PRIMVAC) have shown safety and immunogenicity in Phase I trials, but empirical evidence on their potential population-level value is lacking. This study modelled the expected cost-effectiveness of a PM vaccine administered before pregnancy. Methods: A decision-analytic model compared two strategies from the provider’s perspective: vaccinating women of childbearing age versus no vaccination. The model incorporated gravidity-specific risks of PM, neonatal mortality and the malaria attributable fractions from the literature. Since the efficacy of a PM vaccine for malaria prevention is unknown, we assumed a 40% efficacy and varied this estimate widely in sensitivity analyses. Primary outcomes were incremental cost-effectiveness ratios (ICERs) per perinatal disability adjusted life years (DALYs) averted. Baseline, best-case, and worst-case scenarios were analysed. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty. Cost-effectiveness was defined as an ICER below half of sub- Saharan Africa’s 2025 GDP per capita ($1556). Results: The vaccine was most cost-effective among primigravidae. Under baseline assumptions (40% efficacy; 30% uptake; $5 dose price), the ICER was $321 per perinatal DALY averted for primigravidae versus $4444 for multigravidae. Best-case assumptions further improved cost-effectiveness ($225 vs. $3148). Sensitivity analyses showed robust cost-effectiveness for primigravidae across all plausible parameter ranges, while ICERs in multigravidae were highly sensitive to programme costs and vaccine efficacy. Cost-effectiveness acceptability curves demonstrated that vaccination becomes favourable for primigravidae at relatively low willingness-to-pay thresholds. Conclusions: A placental malaria vaccine delivered before pregnancy has high potential to be cost-effective in endemic areas when targeted to protect primigravidae. These findings support prioritised deployment strategies and highlight the value of early economic modelling to inform vaccine development and policy planning. Full article