Search Results (2,260)

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

Monkeypox (Mpox), a re-emerging zoonotic disease, has garnered global attention due to its evolving epidemiology, diverse clinical manifestations, and significant public health impact. The rapid international spread of the Mpox prompted the World Health Organization to designate the outbreak as a Public Health Emergency of International Concern. Accurate and timely diagnosis is hindered by its critical resemblance to other orthopoxviruses and viral exanthems, underscoring the need for improved diagnostic tools. Point-of-care diagnostic innovations, including CRISPR-based and smartphone-integrated technologies, have revolutionized outbreak management, offering rapid and accurate detection critical for containment and treatment. The effective control of Mpox outbreak underscores the necessity of strengthened global surveillance, equitable healthcare access, rapid diagnostics, the prompt isolation of infected individuals, and the implantation of ring vaccination strategies. The integration of a “One Health” framework that links human, animal, and environmental health is vital for sustained preparedness. Advances in vaccine development, including novel bionic self-adjuvating vaccines and platforms utilizing DNA, mRNA, and viral vectors, highlight promising prevention efforts. However, issues such as vaccine hesitancy, limited immunization coverage and accessibility in resource-constrained regions remain significant barriers. Therapeutic interventions like tecovirimat and the JYNNEOS vaccine demonstrate efficacy but face challenges in scalability and deployment. To address these multifaceted challenges, this review delves into the molecular insights, clinical features, epidemiological trends, and diagnostic challenges posed by Mpox. This review further highlights the critical need for robust scientific evidence and sustained research to inform effective, evidence-based responses, and long-term management strategies for Mpox outbreaks. Full article

Between 2016 and 2018, the state of Minas Gerais, Brazil, experienced its most significant yellow fever (YF) outbreak in 80 years. Yellow fever virus (YFV) circulation persisted afterward, with continued non-human primate (NHP) epizootics and, recently, human cases. In June 2024, YFV RNA was detected in a dead marmoset (Callithrix penicillata) in an urban square in Belo Horizonte (BH), prompting a field investigation in an adjacent park to assess infection in potential mosquito vectors and NHPs. A total of 250 mosquitoes representing nine species were collected at ground and canopy level, of which Aedes fluviatilis and Aedes scapularis comprised 78.8% of the specimens. Haemagogus spp. and Sabethes spp. mosquitoes were not collected, possibly due to the short sampling window during the dry season. No active YFV infection was detected in any of the mosquito pools tested. Eight marmosets (Callithrix penicillata) were captured and tested for arboviral infections. Five out of eight sera, representing both adult and juvenile (less than 17 months old) animals, tested positive for anti-YFV IgM. Interestingly, two adults recaptured in later expeditions revealed seroconversion. One was IgM-positive in July 2024 but negative by September 2024, consistent with the expected decline in IgM levels. The other, initially IgM-negative (as of July 2024), tested positive in April 2025, indicating recent exposure to YFV. These findings provide evidence for the ongoing, low-level circulation of YFV among urban NHPs, posing a continued risk of viral spillover to humans. Moreover, these results highlight the importance of active surveillance in detecting recent infections that would likely be missed by passive monitoring. This integrated approach enhances our understanding of local YF epidemiology and supports early, evidence-based public health interventions to prevent future human outbreaks. Full article

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment. Full article

Cathepsin L (CatL) is a critical protease involved in cleaving the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), facilitating viral entry into host cells. Inhibition of CatL is essential for preventing SARS-CoV-2 cell entry, making it a potential therapeutic target for drug development. Six QSAR models were established to predict the inhibitory activity (expressed as IC₅₀ values) of candidate compounds against CatL. These models were developed using statistical method heuristic methods (HMs), the evolutionary algorithm gene expression programming (GEP), and the ensemble method random forest (RF), along with the kernel-based machine learning algorithm support vector regression (SVR) configured with various kernels: radial basis function (RBF), linear-RBF hybrid (LMIX2-SVR), and linear-RBF-polynomial hybrid (LMIX3-SVR). The particle swarm optimization algorithm was applied to optimize multi-parameter SVM models, ensuring low complexity and fast convergence. The properties of novel CatL inhibitors were explored through molecular docking analysis. The LMIX3-SVR model exhibited the best performance, with an $R^2$ of 0.9676 and 0.9632 for the training set and test set and RMSE values of 0.0834 and 0.0322. Five-fold cross-validation $R_{5-fold}^2$ = 0.9043 and leave-one-out cross-validation $R_{loo}^2$ = 0.9525 demonstrated the strong prediction ability and robustness of the model, which fully proved the correctness of the five selected descriptors. Based on these results, the IC₅₀ values of 578 newly designed compounds were predicted using the HM model, and the top five candidate compounds with the best physicochemical properties were further verified by Property Explorer Applet (PEA). The LMIX3-SVR model significantly advances QSAR modeling for drug discovery, providing a robust tool for designing and screening new drug molecules. This study contributes to the identification of novel CatL inhibitors, which aids in the development of effective therapeutics for SARS-CoV-2. Full article

The aggregation of α-synuclein (αSyn) is a central feature of Parkinson’s disease (PD) and other synucleinopathies. The efficient clearance of αSyn depends largely on the autophagy–lysosomal pathway. Emerging genetic evidence highlights the role of pleckstrin homology and RUN domain-containing M1 protein (PLEKHM1), a critical regulator of autophagosome–lysosome fusion, in the pathogenesis of multiple neurodegenerative diseases. This study investigates the possible effects of increased PLEKHM1 expression on αSyn pathology and neurodegeneration in mice. We utilized a mouse model of PD that is based on A53T-αSyn overexpression, achieved by the stereotactic injection of recombinant adeno-associated viral vectors (rAAV) into the substantia nigra. Additionally, this study explores the effect of PLEKHM1 overexpression on the autophagy–lysosomal pathway under physiological conditions, using transgenic autophagy reporter mice. PLEKHM1 overexpression facilitated the αSyn-induced degeneration of dopaminergic somata in the substantia nigra and degeneration of dopaminergic axon terminals in the striatum. In concert with αSyn expression, PLEKHM1 also potentiated microglial activation. The extent of αSyn pathology, as reported by staining for phosphorylated αSyn, was not affected by PLEKHM1. Using RFP-EGFP-LC3 autophagy reporter mice, rAAV-mediated PLEKHM1 overexpression reduced lysosomal and autolysosomal area, increased LAMP1-LC3 colocalization, and decreased the autolysosome-to-autophagosome ratio. Concurrently, PLEKHM1 overexpression in both genotypes caused p62 accumulation, accompanied by reduced overlap with lysosomal and autophagosomal markers but increased colocalization with autolysosomal markers, indicating impaired cargo degradation during late-stage autophagy. Taken together, elevated PLEKHM1 levels exacerbate neurodegeneration in αSyn-overexpressing mice, possibly by impairing autophagic flux. Now, with in vivo evidence complementing genetic data, alterations in PLEKHM1 expression appear to compromise autophagy, potentially enhancing neuronal vulnerability to secondary insults like αSyn pathology. Full article

Despite improved diagnostic and treatment protocols, cancer remains a leading cause of morbidity and mortality globally. There are increasing rates of certain cancer types, including the highly drug-resistant colorectal cancer, in younger population cohorts. Therapeutic advances in oncology have led to the application of immunotherapy-based agents, including checkpoint inhibitors, antibodies, and adoptive cell therapies. Such immunotherapy approaches are greatly hindered by the tumour microenvironment and lack of specificity. Therapeutic vaccines are an innovative and rapidly advancing area of oncology, having potential for application as mono- and combined therapy in clinical settings, offering long term efficacy against disease recurrence. Advances in vaccine production using gene editing and bioprocessing techniques allows for novel vaccine types, including protein-based subunit vaccines, virus-like particle vaccines, and viral vector- and nucleic acid-based (RNA and DNA) vaccines. Cancer vaccines are designed to deliver specific tumour antigens, which activate anti-cancer cytotoxic T cells and helper T cells to produce immune memory, providing long term anti-cancer action. When coupled with advances in machine learning and artificial intelligence, anti-cancer vaccines may revolutionise oncology protocols and improve patient prognosis. This review aims to discuss current immunotherapy options in cancer treatment and recent advances in anti-cancer vaccine modalities. Full article

Schmallenberg virus (SBV) is a negative-sense RNA virus transmitted by insect vectors, causing arthrogryposis-hydranencephaly syndrome in newborn ruminants. Since its discovery in Germany and the Netherlands in 2011, SBV has rapidly spread across multiple European countries, resulting in significant economic losses in the livestock industry. With the increasing global animal trade and the expanded range of insect transmission, the risk of SBV introduction into non-endemic regions is also rising. As the gold standard for serological testing, the virus neutralization test (VNT) is crucial for tracking the spread of SBV and evaluating the efficacy of vaccines. However, in non-endemic regions, the lack of local viral strains and the biosafety risks associated with introducing foreign strains pose challenges to the implementation of VNT. In this study, we employed reverse genetics techniques using vesicular stomatitis virus (VSV) to substitute the VSV G protein with the envelope glycoproteins of SBV, thereby successfully generating and rescuing the recombinant virus rVSVΔG-eGFP-SBVGPC. The recombinant virus was then thoroughly characterized in terms of SBV Gc protein expression, viral morphology, and growth kinetics. Importantly, rVSVΔG-eGFP-SBVGPC exhibited SBV-specific cell tropism and was capable of reacting with SBV-positive serum, enabling the measurement of neutralizing antibody titers. The results suggest that this recombinant virus can serve as a feasible alternative for SBV neutralization tests, with promising potential for application in serological screening and vaccine evaluation. Full article

Plant viruses have been traditionally considered pathogens restricted to plant hosts. However, recent studies have shown that some plant viruses can infect and replicate in filamentous fungi and oomycetes, suggesting that their host range is broader than previously thought, and that their ecological interactions are more complex. In this study, we investigated the ability of the well-characterized positive-sense RNA plant virus Tobacco mosaic virus (TMV) to replicate in four major phytopathogenic fungi from different taxonomic groups: Botrytis cinerea, Fusarium oxysporum f. sp. lycopersici, Verticillium dahliae, and Monilinia fructicola. Using a recombinant TMV-based vector expressing a green fluorescent protein (TMV-GFP-1056) as reporter, we demonstrated that TMV can enter, replicate, and persist within the mycelia of B. cinerea and V. dahliae—at least through the first subculture. However, it cannot replicate in F. oxysporum f. sp. lycopersici and M. fructicola. RNA interference (RNAi) is a conserved eukaryotic epigenetic mechanism that provides an efficient defence against viruses. We explored the role of RNAi in the interaction between TMV and the mycelia of V. dahliae and B. cinerea. Our results revealed a strong induction of the Dicer-like 1 and Argonaute 1 genes, which are key compounds of the RNA silencing pathway. This RNAi-based response impaired TMV-GFP replication in both fungi. Notably, despite viral replication and RNAi activation, the virulence of V. dahliae and B. cinerea on their respective host plants remained unaffected. These findings reinforce the emerging recognition of cross-kingdom virus transmission and interactions, which likely play a crucial role in pathogen ecology and viral evolution. Understanding these virus–fungus interactions not only sheds light on RNAi interference silencing mechanisms but also suggests that plant viruses like TMV could serve as simple and effective tools for functional genomic studies in fungi, such as in V. dahliae and B. cinerea. Full article

Common bean (Phaseolus vulgaris L.), the world’s most widely grown legume crop, is not only of great commercial importance but is also a vital smallholder crop in low-to-medium-income countries. In sub-Saharan Africa common bean provides consumers with a major proportion of their dietary protein and micronutrients. However, productivity is constrained by viruses, particularly those vectored by aphids and whiteflies, and problems are further compounded by seed-borne transmission. We describe common bean’s major viral threats including the aphid-transmitted RNA viruses bean common mosaic virus and bean common mosaic necrosis virus, and the whitefly-transmitted begomoviruses bean golden mosaic virus and bean golden yellow mosaic virus and discuss how high-throughput sequencing is revealing emerging threats. We discuss how recent work on indirect and direct viral ‘manipulation’ of vector behaviour is influencing modelling of viral epidemics. Viral extended phenotypes also modify legume interactions with beneficial organisms including root-associated microbes, pollinators and the natural enemies of vectors. While problems with common bean tissue culture have constrained transgenic and gene editing approaches to crop protection, topical application of double-stranded RNA molecules could provide a practical protection system compatible with the wide diversity of common bean lines grown in sub-Saharan Africa. Full article

Rice planthoppers are the most destructive pests of rice production and the vectors of rice viruses. Fenmezoditiaz as a novel mesoionic insecticide is used for rice planthopper management by targeting the insect’s neural nicotinic acetylcholine receptor. This study aimed to evaluate the effects of fenmezoditiaz on the acquisition, propagation, and transmission of southern rice black-streaked dwarf virus (SRBSDV) by the white-backed planthopper, Sogatella furcifera (Hemiptera: Delphacida). The results revealed that sublethal concentrations of fenmezoditiaz significantly impaired SRBSDV acquisition and viral replication in S. furcifera. Fenmezoditiaz-treated viruliferous S. furcifera exhibited a lower transmission efficiency of SRBSDV to un-infected rice seedlings. Electrical penetration graph (EPG) recordings revealed prolonged non-probing (NP), salivary secretion (N2/N3), and xylem feeding (N5) durations, alongside shortened phloem contact behavior (N4a/N4b), of fenmezoditiaz-treated individuals, indicating disrupted feeding behaviors, which are critical for reducing viral infection. By reducing viral titers and interfering with phloem ingestion, fenmezoditiaz significantly suppresses SRBSDV transmission. These findings revealed fenmezoditiaz’s dual role in pest control and viral transmission blockage, providing a foundation for incorporation into integrated management of vector-borne plant viruses. Full article

Background/Objectives: Lysozyme-based amyloid aggregates offer a promising platform for RNA delivery due to their stability, cationic nature, biocompatibility, and ability to form well-defined structures. In this study, we evaluated their potential as drug carriers, focusing on the delivery of polyinosinic–polycytidylic acid (Poly(I:C)), an immunostimulatory synthetic RNA. To validate RNA delivery capability and rule out the possibility that observed effects arose from the lysozyme–Poly(I:C) complex itself, small interfering RNA (siRNA) was also used to verify that the successful delivery of intact and functional RNA was the cause of the observed effects. Methods: The aggregates were characterized by particle size, zeta potential, morphology, and RNA encapsulation efficiency. Results: In vitro studies using RAW 264.7 macrophage-like cells demonstrated that Poly(I:C)-loaded aggregates improved RNA uptake and triggered significant immune activation without inducing toxicity. To further confirm the potential of lysozyme amyloids in RNA delivery, GFP siRNA-loaded aggregates were evaluated in A549-GFP cells. A notable decrease in GFP expression, confirmed through confocal microscopy and flow cytometry, confirmed successful intracellular delivery. Conclusions: These results highlight the potential of lysozyme amyloids as non-viral vectors for RNA delivery, with promising applications in immunotherapy. Full article

Hemophilias and hemoglobinopathies—including hemophilias A and B, sickle cell disease (SCD), and β-thalassemia—are debilitating genetic disorders associated with significant global health burdens. While traditional management has centered on factor replacement and transfusions, these approaches remain palliative, with limited access and durability in many regions. Recent advances in immune-based therapeutics (e.g., emicizumab, concizumab, crizanlizumab), viral vector-mediated gene addition (e.g., Roctavian, Hemgenix), and gene-modified autologous stem cell therapies (e.g., Zynteglo, Casgevy) have ushered in a new era of disease-modifying and potentially curative interventions. These therapies offer durable efficacy and improved quality of life, particularly in adult populations. However, implementation remains uneven across global health systems due to high costs, limited infrastructure, and regulatory heterogeneity. Additionally, ethical considerations such as long-term surveillance, informed consent in vulnerable populations, and social perceptions of genetic modification present ongoing challenges. Innovations such as multiplex genome editing, immune-evasive donor platforms, synthetic biology, and AI-driven treatment modeling are poised to expand therapeutic horizons. Equitable access, particularly in regions bearing the highest disease burden, will require collaborative funding strategies, regional capacity building, and inclusive regulatory frameworks. This review summarizes the current landscape of curative therapy, outlines implementation barriers, and calls for coordinated international action to ensure that transformative care reaches all affected individuals worldwide. Full article

This study reviews the role of epidemiology in the United States in the late 19th and early 20th century, which led to recognition that poliomyelitis is an infectious disease and set the stage for subsequent developments in virology and immunology, the development of inactivated and live attenuated polio vaccines, and a dramatic worldwide decrease in poliomyelitis mortality and morbidity. Epidemiological studies in the United States were systematically reviewed from the mid-19th to early 20th centuries. Isolated cases and scattered small outbreaks of poliomyelitis in the mid-19th century led to epidemics of increasing size by the end of the century, causing public consternation, especially as the disease was considered “new” and had a predilection for young children. By the 1890s, the seasonal pattern of epidemics suggested that poliomyelitis might have an infectious etiology, but direct evidence of communicability or contagiousness was lacking, so an infectious etiology was not widely suspected until the early 20th century. Reports of bacterial isolations from spinal fluid and postmortem tissues suggested that poliomyelitis might be a bacterial disease, and simultaneous outbreaks of paralytic disease in humans and animals suggested a possible zoonotic basis. Although experimental studies showed that it was theoretically possible for flies to serve as vectors of poliovirus, and occasional cases of polio were likely caused by fly-borne transfer of poliovirus from human feces to human food, a fly abatement field trial showed convincingly that flies, whether biting or non-biting, could not explain the bulk of cases during polio epidemics. In conclusion, the early application of epidemiological evidence beginning in the late 19th century strongly suggested the infectious nature of the disease, distinct from previously identified conditions. Subsequent advances in virology and immunology from 1909 to 1954 proved that poliomyelitis was a viral disease with no natural animal host and made feasible the development of an inactivated trivalent poliovirus vaccine by Salk, and, subsequently, a live-attenuated trivalent poliovirus vaccine by Sabin. Full article

Background: Dengue infection is a spreading vector borne disease with most severe infection-related fatalities occurring in adults. This study was conducted to explore prognostic indicators of dengue infection severity. Methods: This study included patients aged over 15 years who were diagnosed with dengue viral infection. Data were collected from nine hospitals across all regions of Thailand between January 2019 and December 2022. Diagnosis of dengue infection was confirmed by a positive result for the NS-1 antigen via RT–PCR, IgM antibody, or IgG antibody tests. Data including gender, age, BMI, underlying disease, clinical characteristics and laboratory findings were collected. Multivariable logistic regression with backward elimination was used to identify a set of prognostic factors. Results: The prognostic indicators of severe dengue were age < 55 years (OR = 6.13, p = 0.054), severe bleeding (bleeding from the gastrointestinal tract, hematemesis, melena, menorrhagia, or hematuria) (OR = 20.75, p < 0.001), pleural effusion (OR = 10.23, p < 0.001), and platelet ≤ 100,000 (/µL) (OR = 3.62, p = 0.035). These predictors were able to accurately estimate the severity of dengue infection with an area under the receiver operating curve (AuROC) of 0.836. Conclusions: The proposed four prognostic factors can be applied to predict severe dengue infections. These findings may inform the development of a risk scoring system to forecast severe dengue infection, early detection, and appropriate treatment during sickness. Full article