Search Results (10,867)

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

Genetically modified (GM) lactic acid bacteria (LAB) are gaining attention as tools for innovation in the food sector, health applications, and industrial processes. LAB have long been used safely due to their GRAS/QPS status, making them suitable for improving fermentation and synthesizing specific and beneficial metabolites. Advances in genomics and gene editing have significantly expanded the available tools, ranging from classical mutagenesis to site-specific recombination, homologous recombination in non-coding regions, CRISPR-based systems, and food-grade chromosomal integration. These approaches enable the insertion of desired genes and the development of engineered strains with tailored functionalities. GM-LAB are also being studied as live delivery systems for therapeutic molecules, including cytokines, hormones, antimicrobial peptides, and vaccine antigens. Engineered strains of Lactococcus lactis and Lactobacillus spp. have yielded promising outcomes in applications such as mucosal immunization, modulation of inflammatory and metabolic responses, and inhibition of pathogenic microorganisms, including multidrug-resistant bacteria. From an industrial perspective, several studies highlight their potential for cost-effective recombinant protein production and the synthesis of high-value metabolites through fermentation. However, within the European Union, their use is subject to stringent regulatory oversight, requiring comprehensive molecular and environmental risk assessments, careful evaluation of horizontal gene transfer, and a preference for markerless chromosomal integrations. Despite these constraints, GM-LAB offer significant potential to improve food quality, sustainability, and human health. Full article

Human Papillomavirus (HPV) is one of the most prevalent infections worldwide and a leading cause of cervical cancer, as well as anal, oropharyngeal, penile, vulval, and vaginal cancers. Despite the availability of safe and effective vaccines, coverage beyond female adolescent programmes remains often insufficient, leaving many adolescents and adults unprotected. The World Federation of Public Health Associations (WFPHA) convened a year-long global expert engagement forum to develop evidence-informed policy recommendations to advance HPV elimination. Building on this work, the resulting Call-to-Action urges countries to expand access to boys and adults. Adopting a life-course approach, integrated with screening, equitable access policies, and sustainable financing, can significantly increase coverage and reduce the burden of HPV-related cancers. This article outlines the main outcomes of the Call-to-Action and highlights key priorities for policy and decision makers committed to accelerating HPV elimination. Full article

Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide, with current polysaccharide-based vaccines offering limited serotype coverage, high production costs, and reduced efficacy in vulnerable populations. These limitations have prompted the search for conserved pneumococcal proteins as universal vaccine candidates. Among them, pneumococcal surface protein A (PspA) stands out as a major virulence factor, present in virtually all clinically relevant strains, and capable of interfering with complement activation, opsonophagocytosis, and host defense mechanisms. Over three decades of research have demonstrated PspA’s strong immunogenicity, protective efficacy in multiple animal models, and safety in early-phase clinical trials. Here, we critically review advances in PspA-based vaccine development, including recombinant protein fragments, fusion constructs, nanoparticle formulations, and live-vector platforms. We highlight the structural and immunological determinants underlying its protective potential, while discussing major challenges such as antigenic variability and cross-reactivity across pneumococcal strains expressing distinct PspA clades. By integrating recent experimental and translational findings, this review outlines the opportunities and obstacles for the implementation of serotype-independent PspA-based vaccines. Full article

Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs—including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)—emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks. Full article

Background/Objectives: The efficacy of inactivated foot-and-mouth disease virus (FMDV) vaccines depends on the structural integrity of the 146S virions. However, instability of 146S antigens during vaccine manufacturing and storage can compromise vaccine quality. Despite its high immunogenicity, the Korean serotype O strain O Jincheon (O JC) exhibits poor physical stability. Methods: To enhance antigenic stability while preserving strain-specific antigenicity, we engineered a VP1-substituted recombinant virus, (R) O1 M–O JC_VP1, by integrating the VP1 coding region of O JC into the O1 Manisa (O1 M) backbone. Results: The resulting chimeric virus exhibited significantly improved capsid stability, as demonstrated by an increased melting temperature and enhanced resistance to thermal stress, chloroform exposure, and long-term storage. Importantly, the recombinant antigen maintained its immunogenicity and induced antibody responses comparable to those induced by the parental O JC strain in vaccinated pigs. Conclusions: These findings demonstrate that VP1-direct chimeric engineering can improve capsid stability without compromising antigenicity and provide a practical approach for developing a stable FMDV vaccine. Full article

Background: Hematological patients have a high risk of developing severe COVID-19 (37%). Most mRNA vaccine trials in hematological patients showed a low immunogenicity after two doses, while long-term data are scarce. Methods: In this monocentric retrospective observational study, we evaluated humoral and T cell-mediated immune responses in 230 hematological patients after three doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. Patients were stratified by age, disease type/state, prior COVID-19 infection, and treatment status and regimens (anti-CD20 monoclonal antibodies, BTK and BCL-2 inhibitors, and treatment line). Antibody titer to SARS-CoV-2 was assessed by electrochemiluminescence immunoassay and T cell response by QuantiFERON interferon-γ release assay (IGRA). Data were analyzed using univariate (Fisher’s exact test) and Firth’s bias-reduced penalized-likelihood logistic regression. Results: A robust humoral response was observed with 91.55% of patients developing anti-spike antibodies (GMT 988.83 U/mL). Anti-CD20-bendamustine treatment was associated with a significantly lower antibody positivity compared to untreated subjects. Prior COVID-19 infection significantly boosted both antibody positivity (95.9% vs. 85.2%) and GMT (847.02 U/mL vs. 258.79 U/mL). Conversely, T cell response was suboptimal (36.1% positive), particularly in anti-CD20-bendamustine-treated and multi-treated patients (27.1%), but highest in those treated with BTK inhibitors (50%). Multivariable logistic regression analysis linked multiple treatments to lower T cell response. Following vaccination, 29.1% of patients contracted SARS-CoV-2, but only 0.89% developed severe COVID-19. Conclusions: Three doses of mRNA vaccine elicit a strong humoral but a low T cell response, as detected by IGRA, in hematological patients. These findings underscore the importance of completing vaccination before initiating immunosuppressive therapies. Full article