Search Results (107)

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

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article

Uveal melanoma (UM), the most common primary intraocular malignancy in adults, poses a unique clinical challenge due to its high propensity for liver metastasis and poor responsiveness to conventional therapies. Despite the expanding landscape of immunotherapy in oncology, progress in managing metastatic uveal melanoma (mUM) remains limited, and no universally accepted standard of care has been established. In this review, we examine the current state and evolving strategies in immunotherapy for mUM, focusing on immune checkpoint inhibitors (ICIs), T cell receptor (TCR)-engineered therapies, and tumor-targeted vaccines. We also present a meta-analytical comparison of clinical outcomes between ICI monotherapy and combination regimens, alongside the recently FDA-approved T cell engager tebentafusp. Our analysis indicates that the triple combination of Ipilimumab, anti-PD-1 agents, and tebentafusp significantly enhances objective response rates, disease control rates, 1-year overall survival rates, and median overall survival (mOS) compared to ICI monotherapy alone. However, this enhanced efficacy is accompanied by increased toxicity due to broader immune activation. In contrast, tebentafusp offers superior tumor specificity and a more favorable safety profile in HLA-A*02:01-positive patients, positioning it as a preferred therapeutic option for this genetically defined subset of UM. Additionally, early-phase studies involving dendritic cell-based immunotherapies and peptide vaccines has shown encouraging signs of tumor-specific immune activation, along with improved tolerability. Collectively, this review underscores the urgent need for more precise and effective immunotherapeutic approaches tailored to the unique biology of mUM. Full article

The COVID-19 pandemic has revealed the profound and lasting impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the nervous system. Beyond acute infection, SARS-CoV-2 acts as a potent immunomodulatory agent, disrupting immune homeostasis and contributing to persistent inflammation, autoimmunity, and neurodegeneration. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by a spectrum of neurological symptoms, including cognitive dysfunction, fatigue, neuropathy, and mood disturbances. These are linked to immune dysregulation involving cytokine imbalance, blood–brain barrier (BBB) disruption, glial activation, and T-cell exhaustion. Key biomarkers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NFL) correlate with disease severity and chronicity. This narrative review examines the immunopathological mechanisms underpinning the neurological sequelae of long COVID, focusing on neuroinflammation, endothelial dysfunction, and molecular mimicry. We also assess the role of viral variants in shaping neuroimmune outcomes and explore emerging diagnostic and therapeutic strategies, including biomarker-guided and immune-targeted interventions. By delineating how SARS-CoV-2 reshapes neuroimmune interactions, this review aims to support the development of precision-based diagnostics and targeted therapies for long COVID-related neurological dysfunction. Emerging approaches include immune-modulatory agents (e.g., anti-IL-6), neuroprotective drugs, and strategies for repurposing antiviral or anti-inflammatory compounds in neuro-COVID. Given the high prevalence of comorbidities, personalized therapies guided by biomarkers and patient-specific immune profiles may be essential. Advancements in vaccine technologies and targeted biologics may also hold promise for prevention and disease modification. Finally, continued interdisciplinary research is needed to clarify the complex virus–immune–brain axis in long COVID and inform effective clinical management. Full article

Measles, hepatitis C, and COVID-19 are significant human diseases caused by RNA viruses. While vaccines exist to prevent infections, there are a small number of currently available therapeutic agents that can effectively treat these diseases after infection occurs. This study explores a new therapeutic strategy using a small molecule designated polyprenyl immunostimulant (PI) to increase innate immune responses and combat viral infections. Using a multi-disciplinary approach, this study quantifies the effects of PI in mice and THP-1 cells using flow cytometry to identify immune phenotypic markers and mass spectroscopy to monitor the metabolomic profiles of immune cells perturbed by PI treatment. The metabolomic studies identified that sphinganine and ceramide, which are precursors of sphingosine-1-phosphate (S1P), were the common metabolites upregulated in THP-1 and mice blood. Sphingosine-1-phosphate can mediate the trafficking of T cells, whereas ceramide can signal the activation and proliferation of T cells, thereby modulating the mammalian host’s immunity. To demonstrate proof-of-principle, a case study was conducted to examine the benefit of administering PI to improve the outcomes of a feline co-infected with two distinct RNA viruses—feline leukemia virus and feline infectious peritonitis virus. Both viruses produce deadly symptoms that closely resemble RNA viruses that infect humans. The results identify quantifiable cellular and metabolic markers arising from PI treatment that can be used to establish a platform measuring the efficacy of PI in modulating the innate immune system. Full article

Background: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. Clinical trials in advanced cancer patients have demonstrated low toxicity, high immunogenicity and clinical benefit. The goal of this study was to identify circulating biomarkers of clinical outcome. Methods: Eighteen patients with stage IIIb/IV non-small-cell lung cancer (NSCLC) were injected with racotumomab-alum as switch maintenance therapy after first-line chemotherapy. Treatment was administered until severe performance status worsening or toxicity. The frequencies of innate and adaptive lymphocytes were assessed by flow cytometry. Circulating factors were measured using multi-analyte flow assay kits. Results: The median overall survival was 16.5 months. Twenty-seven percent of patients were classified as long-term survivors. Patients with lower baseline frequencies of CD4+Tregs and central memory (CM) CD8+T cells displayed longer survival rates. Furthermore, higher baseline frequencies of NKT cells and a high CD8+T/CD4+Treg ratio were associated with longer survival. Interestingly, patients with significantly lower levels of effector memory (EM) CD8+T cells survived longer. The levels of NKT cells and terminal effector memory (EMRA) CD8+T cells were higher in long-term survivors in comparison with short-term survivors in post-immune samples. As expected, the ratio of CD8+T/CD4+Tregs showed significantly higher values during treatment in patients with clinical benefits. Regarding serum factors, pro-tumorigenic cytokines significantly increased during treatment in poor survivors. Conclusions: In advanced NSCLC patients receiving racotumomab-alum vaccine, longer survival could be associated with a unique profile of circulating lymphocyte subsets at baseline and during treatment. Additionally, certain pro-tumor-related cytokines increased in short-term survivors. These results should be confirmed in larger randomized clinical trials. This clinical trial was registered in the Cuban Clinical Trials Register (RPCE00000279). Full article

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Conventional therapies are frequently limited by tumor heterogeneity and the immunosuppressive tumor microenvironment (TME). Dendritic cells (DCs), central to orchestrating antitumor immunity, have become key targets for HCC immunotherapy. This review examines the biological functions of DC subsets (cDC1, cDC2, pDC, and moDC) and their roles in initiating and modulating immune responses against HCC. We detail the mechanisms underlying DC impairment within the TME, including suppression by regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs). Additionally, we discuss novel DC-based therapeutic strategies, such as DC-based vaccines designed to enhance antigen presentation and T cell activation. Combining DC vaccines with immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 and CTLA-4 blockers, demonstrates synergistic effects that can overcome immune evasion and improve clinical outcomes. Despite progress, challenges related to DC subset heterogeneity, TME complexity, and patient variability require the further optimization and personalization of DC-based therapies. Future research should focus on refining these strategies, leveraging advanced technologies like genomic profiling and artificial intelligence, to maximize therapeutic efficacy and revolutionize HCC treatment. By restoring DC function and reprogramming the TME, DC-based immunotherapy holds immense potential to transform the management of HCC and improve patient survival. Full article

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases. Full article

Monitoring the immune response to vaccination encompasses both significant challenges and promising opportunities for scientific advancement. The primary challenge lies in the inherent complexity and interindividual variability of immune responses, influenced by factors including age, genetic background, and prior immunological history. This variability necessitates the development of sophisticated, highly sensitive assays capable of accurately quantifying immune parameters such as antibody titers, T-cell responses, and cytokine profiles. Furthermore, the temporal dynamics of the immune response require comprehensive longitudinal studies to elucidate the durability and quality of vaccine-induced immunity. Challenges of this magnitude pave the way for immunological research advancements and diagnostic methodologies. Cutting-edge monitoring techniques, such as high-throughput sequencing and advanced flow cytometry, enable deeper insights into the mechanistic underpinnings of vaccine efficacy and contribute to the iterative design of more effective vaccines. Additionally, the integration of analytical tools holds the potential to predict immune responses and tailor personalized vaccination strategies. This will be addressed in this review to provide insight for enhancing public health outcomes and fortifying preparedness against future infectious disease threats. Full article

Pancreatic cancer is a deadly disease with a low survival rate, particularly in its advanced stages. Advanced pancreatic cancer remains a major clinical challenge due to limited treatment options. Surgical resection may not always be feasible, and traditional chemotherapy often shows restricted effectiveness. As a result, researchers are exploring a multifaceted therapeutic approach targeting the genetic and molecular drivers of the disease. A combination of molecular profiling and targeted therapies are being investigated to improve outcomes and address the shortcomings of traditional treatments. The focus of this review is to provide a summary of current and completed clinical trials for the treatment of advanced pancreatic cancer. This includes adagrasib (a KRAS inhibitor), olaparib (a PARP inhibitor for BRCA mutations), APG-1387 (an IAP antagonist), minnelide (an anti-stromal agent), arimastat (an MMP inhibitor), MK-0646 (an IGF1R inhibitor), sirolimus (an mTOR inhibitor), and metabolic inhibitors. These agents are being evaluated both as standalone treatments and in combination with standard therapy. Furthermore, we have summarized novel approaches such as cancer vaccines and ablation techniques as emerging strategies in the treatment of advanced pancreatic cancer. We have also examined the challenges in treating advanced pancreatic cancer and the factors contributing to therapeutic failure, which may offer valuable insights for developing more effective treatment strategies and innovative drug designs. Full article

(1) Background: Human Leukocyte Antigen (HLA) genetics substantially affect viral infection outcomes. SARS-CoV-2 continues to evolve, potentially escaping HLA presentation and hindering immune control. However, studies on HLA alleles in diverse non-Western populations remain limited. Therefore, we aimed to investigate whether mutations in successive SARS-CoV-2 variants have led to viral escape from common HLA class I alleles in the Saudi Arabian population. (2) Methods: The binding affinities of spike protein epitopes for common Saudi HLA alleles (HLA-A02:01, HLA-C06:02, and HLA-B51:01) were predicted across major SARS-CoV-2 strains using NetMHCpan. One-way ANOVA, one-sample t-tests, and pairwise chi-square analyses were performed to assess the differences in binding affinities and epitope binding categories among strains. (3) Results: One-way ANOVA revealed significant differences in binding affinities among SARS-CoV-2 strains for HLA-A02:01 and HLA-C06:02, but not for HLA-B51:01. One-sample t-tests revealed significant differences in mean binding affinity scores compared to a theoretical mean of 0 for all strain–HLA allele combinations, except for HLA-B51:01. Pairwise chi-square analyses identified significant differences in the epitope binding category distribution between Alpha and Epsilon strains, as well as between Epsilon and Gamma strains for HLA-B51:01. (4) Conclusions: The evolution of SARS-CoV-2 has enabled its escape from common HLA alleles in Saudis. Tracking population-specific HLA binding profiles is crucial for the elucidation of associated evasion mechanisms and guiding the design of future vaccines against COVID-19. Full article

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) characterized by complement dysregulation, leading to microvascular thrombosis and multi-organ injury. TMAs are defined by thrombocytopenia, microangiopathic hemolytic anemia and organ dysfunction caused by small-vessel thrombosis. Unlike thrombotic thrombocytopenic purpura, which results from severe ADAMTS13 deficiency, aHUS is driven by uncontrolled activation of the alternative complement pathway. While the kidneys are most frequently affected, other vital organs can also be involved. Genetic susceptibility contributes significantly to disease risk, but a trigger such as infection, pregnancy or autoimmune disease is usually required. Diagnosis is challenging due to overlapping features with other TMAs and relies on exclusion and complement testing. C5 inhibitors, such as eculizumab and ravulizumab, have revolutionized treatment but necessitate prophylactic vaccination and ongoing clinical surveillance. While these therapies provide effective disease control, discontinuing treatment remains complex, especially in patients with complement gene mutations. New therapies targeting various points in the complement cascade are under investigation and may offer safer, more cost-effective options. Progress in genetic profiling and biomarker discovery is essential for earlier diagnosis, individualized therapy and relapse prevention. This review highlights recent advances in the understanding of aHUS pathophysiology, clinical features and evolving therapeutic strategies aimed at improving patient outcomes. Full article

Pharmacogenomics is revolutionizing precision medicine by enabling tailored therapeutic strategies based on an individual genetic and molecular profile. Circular RNAs (circRNAs), a distinct subclass of endogenous non-coding RNAs, have recently emerged as key regulators of drug resistance, tumor progression, and therapeutic responses. Their covalently closed circular structure provides exceptional stability and resistance to exonuclease degradation, positioning them as reliable biomarkers and novel therapeutic targets in cancer management. This review provides a comprehensive analysis of the interplay between circRNAs and pharmacogenomics, focusing on their role in modulating drug metabolism, therapeutic efficacy, and toxicity profiles. We examine how circRNA-mediated regulatory networks influence chemotherapy resistance, alter targeted therapy responses, and impact immunotherapy outcomes. Additionally, we discuss emerging experimental tools and bioinformatics techniques for studying circRNAs, including multi-omics integration, machine learning-driven biomarker discovery, and high-throughput sequencing technologies. Beyond their diagnostic potential, circRNAs are being actively explored as therapeutic agents and drug delivery vehicles. Recent advancements in circRNA-based vaccines, engineered CAR-T cells, and synthetic circRNA therapeutics highlight their transformative potential in oncology. Furthermore, we address the challenges of standardization, reproducibility, and clinical translation, emphasizing the need for rigorous biomarker validation and regulatory frameworks to facilitate their integration into clinical practice. By incorporating circRNA profiling into pharmacogenomic strategies, this review underscores a paradigm shift toward highly personalized cancer therapies. circRNAs hold immense potential to overcome drug resistance, enhance treatment efficacy, and optimize patient outcomes, marking a significant advancement in precision oncology. Full article

Background/Objectives: Murine models play a key role in guiding formulation and immunogenicity studies across various vaccine platforms, including mRNA-based vaccines. Typically, a narrow age range (6 to 8 weeks) is used in these studies. Here, we investigated whether widening this age range could provide greater flexibility in experimental design without impacting pre-clinical outcomes. Methods: To achieve this, we evaluated two commonly used lipid nanoparticle (LNP) formulations (based on SM102 and ALC-0315 ionizable lipids) containing either firefly luciferase or ovalbumin mRNA in female BALB/c mice aged 4, 8, and 16 weeks. LNPs were prepared and purified via microfluidics, and their size, polydispersity, zeta potential, and encapsulation efficiency were measured. Mice were injected intramuscularly, and the in vivo bioluminescence and antibody titers were measured to evaluate mRNA expression profiles and immunogenicity across the three age groups. Results: Our findings show that the 4-week-old mice exhibited higher protein expression following mRNA administration compared to the older groups; however, no significant differences were observed between the 8- and 16-week-old mice. Despite the initial higher protein expression, the antibody responses after the prime dose were lower in the 4-week-old mice compared to the other two groups. However, following the booster dose, antibody levels were comparable across all three age groups. Conclusions: By identifying a broader age range window, we provide greater flexibility in study design, enhance data comparability across studies, and promote more efficient use of animal resources, all while maintaining reliable and representative results in these murine models. Full article