Search Results (435)

Intestinal infections caused by Salmonella enterica serovar Typhi (S. Typhi) remain a global health concern, making preventive strategies and diagnostic tools essential. This study aimed to identify mimotope peptides of the Vi antigen using phage display and assess their recognition by rabbit and 46 human sera, as well as their potential for diagnosis and immunogen design. Rabbits were immunized with the Vi antigen (AgVi) from S. Typhi ATCC 6539, and sera-derived IgG was used for phage biopanning. DNA sequences from selected phagotopes were synthesized as Salmonella mimotope peptides (SMPs), either linear or KLH-conjugated. Their reactivity was tested with ELISAs against AgVi and SMPs, using both rabbit sera and 46 human serum samples. Ten phagotopes were identified, with a consensus motif (D/G–A/V–x–P–x–x–G–x–x–x–x–x), suggesting α-helix structures. Immunization with KLH-conjugated peptides generated specific antibodies, particularly SMPVi/5 and SMPVi/10, which recognized AgVi and their respective peptides. Competitive inhibition assays confirmed that SMPVi/5 reduced the anti-AgVi binding in a dose-dependent manner. In human sera, AgVi recognition occurred in 52% of samples, while SMPVi/5 and SMPVi/10 were recognized in 45%. Overall, SMPVi/5 demonstrated immunogenicity and functional mimicry, supporting its use as a synthetic reagent for serological assays and as a candidate for immunogen design. Full article

The capsid protein pE120R of African swine fever virus (ASFV) is highly immunogenic and is thought to play an important role in viral replication, yet its molecular characteristics and functions during infection remain poorly understood. Here, we generated two monoclonal antibodies (mAbs), 1C11 and 3G7, against ASFV pE120R and characterized their specificity and utility. Epitope mapping showed that 1C11 recognized the linear epitope ¹⁰⁹KKHLFP¹¹⁴, whereas 3G7 recognized ¹¹²LFPKL¹¹⁶. These antibodies enabled analysis of pE120R expression and localization during ASFV infection, demonstrating that pE120R is expressed at a late stage and partially co-localizes with the structural protein p54 in viral factories. Together, these results provide valuable immunological tools for further investigation of pE120R in ASFV replication and pathogenesis. Full article

Background/Objectives: Inflammatory bowel disease (IBD) management has evolved from conventional therapies to advanced biologics and targeted small molecules; however, clinical practice often relies on empirical treatment sequencing rather than individualized approaches. The heterogeneity of IBD phenotypes, variable treatment responses, and expanding therapeutic options necessitate a shift toward precision medicine. This review aims to synthesize current evidence on personalizing IBD therapy and provide an implementation framework for clinical practice. Methods: A narrative review was conducted encompassing peer-reviewed literature, recent network meta-analyses, and clinical guidelines. Evidence was gathered on treat-to-target strategies, therapeutic drug monitoring (TDM), clinical decision support systems, artificial intelligence applications, multi-omics platforms (genomics, transcriptomics, microbiome, metabolomics), advanced imaging modalities, and special populations including pediatric patients and pregnant women. Results: Treat-to-target strategies incorporating endoscopic and biochemical endpoints improve long-term outcomes when individualized to patient-disease factors. TDM-guided optimization enhances biologic efficacy and reduces immunogenicity. Emerging AI tools and multi-omics platforms show promise in predicting treatment response and patient stratification. Network meta-analyses provide comparative effectiveness estimates guiding advanced therapy selection in both Crohn’s disease and ulcerative colitis. Implementation of precision medicine frameworks remains constrained by regulatory, economic, and technical barriers. Conclusions: Personalizing IBD therapy through integration of precision medicine tools, patient-specific factors, and comparative effectiveness data represents the future of IBD management. Overcoming implementation barriers through standardized frameworks and multidisciplinary collaboration is essential to translate these advances into routine clinical practice. Full article

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with a five-year survival rate of only 26%, primarily due to late-stage diagnosis and limited treatment options. Exosomes, nanosized extracellular vesicles released by nearly all cell types, have emerged as promising tools in both diagnostics and therapeutics. Their unique composition containing proteins, lipids, and nucleic acids reflects the molecular profile of their cell of origin, making them excellent candidates for non-invasive early detection biomarkers. For therapeutic applications, exosomes offer biocompatible, low-immunogenicity platforms capable of delivering diverse therapeutic agents, including small molecules, siRNAs, and antimetabolites, directly to tumor cells while minimizing systemic toxicity. Functionalization strategies, such as folic acid tagging, have further enhanced tumor specificity, especially in cancers with high folate receptors. However, clinical translation is hindered by challenges including lack of standardized isolation and characterization methods, high production costs, and regulatory uncertainties. Despite these limitations, ongoing research continues to optimize exosome production, targeting, and integration with conventional therapies. Milk- and colostrum-derived exosomes have shown promising potential due to their abundance, scalability, oral bioavailability, and safety. Collectively, exosomes represent a transformative approach in lung cancer management, with the potential to improve early diagnosis, enhance therapeutic efficacy, and reduce adverse effects, thereby offering a path toward more personalized and effective cancer care. Full article

As a non-invasive mucosal immunization strategy, intranasal vaccines are highly promising for preventing respiratory infectious diseases. Among them, recombinant subunit vaccines represent a safe and ideal option, as they induce targeted mucosal immunity without the safety risks associated with live-vectored or nucleic acid vaccines. However, nasal mucosal defenses rapidly clear antigens before immune activation, limiting protective efficacy. Therefore, intranasal vaccine adjuvants—key regulators of immune response intensity, duration, and type—are essential to overcome mucosal tolerance and improve immunogenicity. Based on a systematic search and analysis of 127 peer-reviewed articles (2010–2026) in PubMed, Web of Science, and Embase, this study comprehensively summarizes the mechanisms, applications, and limitations of existing and candidate adjuvants for intranasal vaccines. This review systematically categorizes and discusses the nasal mucosal barrier, major adjuvant types (e.g., pattern recognition receptor agonists, cytokine adjuvants, and carrier adjuvants), and their mechanisms of action. It also identifies key bottlenecks: insufficient mucosal targeting, inconsistent global safety evaluation standards for adjuvants, and interference from pre-existing antibodies in humans. Furthermore, this review highlights future development directions, including biomimetic adjuvants, pH-responsive nanoadjuvants, and thermostable vaccine formulations. This systematic review clarifies key scientific and technical barriers in intranasal vaccine adjuvant development. The findings provide valuable references for advancing the translation of intranasal vaccines from emergency countermeasures to routine, accessible preventive tools for respiratory infectious diseases. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are dangerous respiratory pathogens with high pandemic potential. Since 2021, these two viruses have been co-circulating, which implies additional risks of co-infection with both pathogens. Prophylactic vaccination is widely recognized as the most effective way to prevent COVID-19 and influenza and to reduce the severity of these diseases. This review analyzes recent data on the simultaneous circulation of influenza and SARS-CoV-2 viruses worldwide, including epidemiological data and the pathogenetic mechanisms of co-infection. Next, we focus on current approaches to simultaneous and combined vaccination against influenza and COVID-19. We outline the types of vaccines and summarize the available findings on the effectiveness and safety of co-vaccination. Methods: A comprehensive search was conducted using PubMed, Scopus, Web of Science, and ClinicalTrials to identify data relevant to SARS-CoV-2 and influenza co-circulation and dual vaccination. Results: Influenza and SARS-CoV-2 cause similar symptoms, and co-infection can significantly enhance the risks of pneumonia and acute respiratory distress syndrome progressing with a poor outcome, especially among children and the elderly. A range of influenza and COVID-19 vaccines built on different technological platforms is currently available on the market, with proven effectiveness, immunogenicity, and safety. A co-vaccination approach is more convenient for patients and is associated with better response to treatment, while also improving vaccine coverage and compliance and offering significant resource savings for healthcare systems. Conclusions: The concurrent circulation of SARS-CoV-2 and influenza viruses presents a growing public health challenge. Simultaneous and combination vaccination strategies have emerged as effective tools to streamline immunization, enhance protection, and reduce healthcare burden. Future studies should elucidate the mechanisms of the exacerbation of respiratory disease caused by co-infection, as well as the optimal strategies for co-administering influenza and COVID-19 vaccines for long-term control of seasonal and potentially pandemic respiratory viruses. Full article

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

Equine Infectious Anemia (EIA) is a retroviral disease of equids, for which there is no vaccine particularly adapted to American viral strains. In this work we searched for possible epitope regions for the surface proteins gp90 and gp45, rationally employing the latest available bioinformatics tools that constitute the state of the art in the field. We selected eight regions that contain numerous overlapping epitopes that have a high coverage amongst American viral strains and designed a chimeric envelope protein with those proteins fused in tandem as a novel vaccine candidate. In silico predictors were used to analyze chimeric protein physicochemical and immunogenic properties, as well as its allergenicity and toxicity. Protein structure was predicted and validated, and its ability to trigger cytotoxic immune responses was predicted by molecular docking to ELA alleles. The proposed sequence is predicted to be highly immunogenic and sets the base for a novel EIAV vaccine that could be used to protect against several American field strains. Full article

Aptamers, short single-stranded DNA or RNA oligonucleotides, are emerging as transformative tools in cardiology for the diagnosis, treatment, and theranostics of cardiovascular diseases (CVDs). This review highlights their dual utility. In diagnostics, aptamers enable the construction of highly sensitive biosensors for key cardiac biomarkers (e.g., troponins, myoglobin, C-reactive protein, natriuretic peptides), outperforming conventional assays and enabling early detection and point-of-care testing. Therapeutically, aptamers offer targeted, controllable, and reversible anticoagulation, as demonstrated by clinical-stage candidates like BT200 (anti-vWF) and NU172 (anti-thrombin), whose action can be rapidly reversed with antidote oligonucleotides. Furthermore, aptamers serve as precision delivery vehicles (e.g., Gint4.T, RNA-Apt30) for transporting therapeutic peptides or nucleic acids specifically to cardiomyocytes. Recent integration with nanomaterials (quantum dots, graphene, liposomes, DNA origami) has led to advanced biosensing and drug delivery platforms. Despite challenges like stability and the polyethylene glycol (PEG) immunogenicity, ongoing clinical trials underscore the significant potential of aptamer technology to bridge precise diagnostics and targeted therapy, paving the way for innovative, personalized CVD interventions.) Full article

Background/Objectives: Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) may cause severe complications and death in children. It is also a common cause of outbreaks in the Asia-Pacific Region. Incidence among children 1 to <2 years was over 3000/100,000 population in China. A systematic review and meta-analysis was performed to review evidence on vaccine efficacy (VE), immunogenicity, and safety of two doses of EV71 vaccine in children. Methods: Randomized controlled trials (RCTs) comparing EV71 vaccine with placebo or with another EV71 vaccine in children and adolescents aged ≤18 years were searched on PubMed, Medline, Embase, CENTRAL, and CNKI (Chinese) in week 5 November 2024. The reference list of each study and the websites of vaccine manufacturers were also searched. The Cochrane Risk of Bias 2 tool (RoB2) was used to assess the risk of bias. VE, immunogenicity (including seropositive rate, seroconversion rate, geometric mean titer (GMT), Geometric Mean Fold Increase (GMFI)), and rate of adverse events were analyzed. Results: A total of 4199 articles were identified, and 25 studies were finally included. VE (%) against EV71 HFMD in children aged ≤5 years at 12 months was 94.8% (95%CI 87.2–97.9) for Sinovac and 90.9% (95%CI 70.4–97.2) for Wuhan Institute of Biological Products (WIBP), while the Chinese Academy of Medical Sciences (CAMS) reported 97.4% (95%CI 92.9–99.0) at 11 months. At 1 month after the second dose, 99.19% (95%CI 98.15–99.65) of children aged ≤5 years in the vaccine group were seropositive, and 96.30% (95%CI 92.71–98.17) achieved seroconversion. GMT at 1 month after the second dose in the vaccine group was 46.78 (95%CI 26.18–83.61) times that in the placebo group. GMFI at 1 month after the second dose in the vaccine group was 28.41 (95%CI 22.18–36.39) times that of the placebo group. The rate of serious adverse events (AEs) was lower in the vaccine group than the placebo group (1.23% (95%CI 0.58–2.69) vs. 1.34% (95%CI 0.58–3.07)) at 1 month after the second dose. There was no significant difference in other adverse events between the vaccine and placebo groups. Conclusions: EV71 vaccines were effective, immunogenic and safe. Areas with a high incidence of EV71 may consider introducing EV71 vaccines. Full article

Extracellular vesicles (EVs) have emerged as promising tools for cancer diagnosis and therapy owing to their excellent biocompatibility, low immunogenicity, and ability to transport diverse bioactive molecules. This review summarizes recent advances in EVs research, focusing on isolation and detection technologies, their diagnostic and therapeutic applications in oncology, and the key challenges limiting clinical translation. Conventional EVs isolation methods, including ultracentrifugation, density-gradient centrifugation, and polymer-based precipitation, are discussed alongside emerging strategies such as immunoaffinity enrichment, microfluidic separation, lipid-mediated isolation, and thermophoretic enrichment, with comparative evaluation of their yield, purity, cost, and scalability. In cancer diagnosis, EV-associated biomolecules, such as miRNAs, mRNAs, proteins, and lncRNAs, show strong potential as liquid biopsy biomarkers for noninvasive early detection and dynamic disease monitoring. In therapeutic contexts, EVs serve as versatile carriers for gene molecules, chemotherapeutic agents, and small-molecule drugs, and can enhance immunotherapy and RNA-based treatments. Importantly, EVs released from metabolically active tissues, particularly skeletal muscle, contribute to systemic immune regulation and metabolic homeostasis, and their biogenesis and molecular cargo can be influenced by physical activity and exercise-related nutritional status. These insights highlight the need to integrate microengineering technologies, biomolecular profiling, standardized manufacturing systems, and lifestyle-related factors such as exercise and nutrition to accelerate the clinical translation of EV-based strategies in precision oncology and regenerative medicine. Full article

Breast cancer continues to be a major challenge in global health, in part due to significant inequalities in access to costly diagnostic and therapeutic technologies based on antibodies. Their manufacturing requires complex and expensive bioproduction systems, resulting in limited availability of these tools—essential for early detection and targeted treatment—in many regions, particularly in Latin America. This gap has highlighted the need for cost-effective and scalable theranostic alternatives, increasing interest in aptamers. Obtained through SELEX technology, aptamers are synthetic DNA or RNA oligomers that fold into functional structures. Among their advantages are high affinity for their target, low immunogenicity, and chemical synthesis, which assures reproducible production. Aptamers have expanded the landscape of diagnostic platforms through the development of sensitive aptasensors, liquid biopsy strategies, and imaging systems based on nanomedicines. They also contribute to targeted therapy by recognizing cancer biomarkers selectively and enabling controlled drug delivery. This review presents a critical summary of advances in aptamer-based theranostics for breast cancer, addressing molecular mechanisms, structural folding, selective ligand binding, and nanomaterial interfacing. We also discuss applications in extracellular vesicle capture, cancer stem cell detection, and therapeutic conjugates, emphasizing their advantages and limitations relative to approaches based on antibodies. Overall, current advances show aptamers as emerging tools capable of democratizing precision oncology, particularly in regions where access to advanced technologies remains limited. Full article

Neoantigen vaccines have revitalized cancer vaccination by targeting tumor-specific mutant epitopes largely absent from central tolerance. Yet, clinical benefits remain inconsistent, in part because conventional vaccine platforms often do not reliably deliver antigens within an inflammatory tumor context, struggle to overcome immunosuppressive tumor microenvironments, and may not rapidly adapt to tumor heterogeneity and evolution. Oncolytic viruses (OVs) provide a mechanistically distinct route to “vaccinate in situ” by coupling tumor-selective infection and immunogenic cancer cell death with local innate immune activation, antigen release, and remodeling of the tumor microenvironment. In parallel, advances in sequencing, neoantigen prediction (e.g., updated NetMHCpan and MHCflurry tools as of 2025), and antigen presentation validation have enabled rational selection of patient-specific targets. At the same time, modern OV engineering supports insertion of neoantigen payloads and immune-modulatory transgenes. Here, we summarized principles that underpin neoantigen-encoded OVs as personalized cancer vaccines, emphasizing how OV adjuvanticity and antigenicity interact to drive priming, epitope spreading, and durable systemic immunity. We discussed major OV platforms with respect to payload capacity, expression control, manufacturability, and clinical track records, including lessons learned from approved or late-stage OVs such as talimogene laherparepvec (T-VEC) and teserpaturev/G47Δ. We also discussed design choices for encoding neoantigens (polyepitope strings, minigenes, long peptides; class I/II balancing), prioritizing translational biomarkers and immune-monitoring strategies, and outlining regulatory and GMP considerations for “platform-plus-variable insert” products. Finally, we propose a pragmatic clinical workflow for rapid personalization to maximize therapeutic index. Tightly integrating neoantigen science with immunovirotherapy, including recent 2025 preclinical advances like oncolytic adenovirus neoantigen delivery sensitizing low-TMB tumors to PD-1 blockade, could enable next-generation personalized cancer vaccines capable of converting “cold” tumors into responsive, systemically controlled disease. Full article

Background/Objectives: African swine fever is currently the most devastating viral disease affecting domestic and wild suids, causing major economic losses and severe impacts on natural populations. Oral immunization could become an important tool to control the panzootic and support wild pig conservation. However, this requires safe and effective vaccines, baits accepted by target species, and vaccine reservoirs that reliably release the vaccine during bait intake while maintaining vaccine integrity. Methods: We evaluated different bait types and vaccine containers in four wild Suiformes species, including Eurasian wild boar. In the same wild boar, we assessed oral vaccination with the live attenuated vaccine candidate “ASFV-G-ΔI177L”. Environmental monitoring approaches were applied to detect potential virus shedding, and vaccine immunogenicity and dissemination were evaluated. Vaccine stability was tested in vitro in two container types under different temperature conditions. Results: Bait uptake and container performance varied between manufacturers and among species. Environmental samples were largely negative for vaccine virus genome under controlled laboratory conditions, with only a few positive cotton ropes (0.43% of all samples). After oral bait vaccination, 45% (9/20) of wild boar seroconverted, with a higher proportion in animals receiving the vaccine in the slightly less attractive bait (gelatine-based). Vaccine virus dissemination was limited to a small number of organs, including gastrohepatic and mandibular lymph nodes. Conclusions: Our findings demonstrate that wild pigs can be vaccinated orally with “ASFV-G-ΔI177L” while virus shedding appears minimal. Although the tested baits show potential for multiple target species, baits and containers require optimization. Environmental monitoring methods also need refinement for field application. Full article

Glioblastoma multiforme (GBM) remains the most aggressive and treatment-refractory form of primary brain tumor in adults, characterized by rapid proliferation, intratumoral heterogeneity and resistance to current therapies. Despite therapeutic advancements in surgical resection, radiotherapy and chemotherapy, clinical outcomes remain poor, underscoring the need for innovative molecular strategies. This review examines the therapeutic potential of CRISPR/Cas9 genome-editing technologies in GBM, highlighting their ability to model, dissect and potentially correct the genetic alterations that drive GBM tumorigenesis. Key molecular targets, such as EGFR, PTEN, TP53, NF1 and PIK3CA, are discussed within the context of GBM’s mutational and signaling landscape. We further outline emerging CRISPR applications in preclinical models, the current status of CRISPR-based clinical trials and the major barriers hindering translation, including off-target effects, immunogenicity and the challenge of delivering gene-editing systems across the blood–brain barrier. Particular emphasis is placed on delivery technologies, viral and non-viral vectors, including lipid nanoparticles, polymeric systems, inorganic nanocarriers and DNA nanostructures, which are rapidly evolving to improve precision, safety and CNS penetrance. Collectively, this review highlights CRISPR/Cas9 as a powerful tool whose integration with molecular neuro-oncology and precision medicine may ultimately shift GBM treatment toward more personalized and durable therapeutic interventions. Full article