Search Results (26,445)

Background: Predictive modeling of vaccine stability is an essential tool for accelerating development and ensuring product quality, particularly when long-term data are limited. To ensure high-quality input for accurate stability predictions, it is often necessary to allocate substantial analytical resources. Methods: This study demonstrates that integrating high-throughput screening (HTS) techniques such as ultraviolet–visible spectrophotometry (UV-VIS), intrinsic fluorescence and dynamic light scattering (DLS) with Advanced Kinetics Modeling (AKM) results in a synergistic approach, facilitating the development of robust predictive stability models. Results: Here, we applied AKM to a glycoconjugate vaccine targeting extra-intestinal pathogenic Escherichia coli (ExPEC). The aggregation processes observed via size-exclusion high-performance liquid chromatography (SE-HPLC), DLS, turbidity by UV-Vis absorbance and local changes in tryptophan microenvironment captured by intrinsic fluorescence were effectively described by the developed kinetic models. Conclusions: Using accelerated stability data across multiple temperatures, AKM successfully described key degradation pathways. Furthermore, the HTS assay results showed strong correlation with SE-HPLC data, indicating that these assays provide an efficient alternative requiring minimal analytical resources, material, and time. Full article

Early-onset infection caused by Streptococcus agalactiae (Group B Streptococcus, GBS) may occur during gestation or delivery and can lead to severe neonatal sepsis, meningitis, or pneumonia. Discordant GBS infections in twin gestations are rare. We report a fatal case of early-onset GBS infection in dichorionic–diamniotic twins conceived via IVF and delivered by caesarean section at 32 weeks’ gestation due to discordant fetal growth and abnormal Doppler indices in Twin A (Umbilical Artery PI = 1.4; Middle Cerebral Artery PI = 1.5). Twin A had Apgar scores of 3, 5, and 5 and rapidly developed tachycardia, respiratory distress, and systemic infection, while Twin B, with Apgar scores of 7, 8, and 9, remained clinically stable. Both infants were admitted to the NICU and underwent routine blood, urine, and cerebrospinal fluid testing. Despite the prompt initiation of parenteral ceftriaxone and respiratory support, Twin A deteriorated rapidly and died within 28 h. GBS was isolated from Twin A’s blood culture, and maternal placental tissue and high vaginal samples collected before antibiotic administration also grew GBS, with all isolates demonstrating identical antimicrobial resistance profiles. Molecular analysis revealed matching rib1 and alp2/3 gene patterns in isolates from the mother and Twin A. Maternal anovaginal immunochromatography at delivery was positive, whereas screening cultures obtained at 29 weeks’ gestation were negative. This case highlights the limitations of culture-based GBS screening in high-risk pregnancies and preterm deliveries and underscores the potential value of molecular assays and point-of-care testing to improve detection of S. agalactiae throughout pregnancy and the peripartum period. Emerging preventive strategies, including modulation of the genital microbiome and maternal vaccination aligned with WHO recommendations, may further reduce the burden of neonatal GBS disease. Full article

Respiratory syncytial virus (RSV) imposes a substantial burden of severe acute respiratory infection (SARI), especially in young children and the elderly. Methods: We describe RSV epidemiology among hospitalized SARI patients at the Ibn Sina University Hospital Center (Rabat, Morocco) from 1 January 2021, to 31 December 2025, using multiplex PCR (BioFire^® RP2.1plus or Xpert^® SARS-CoV-2/Flu/RSV). Results: Among 4604SARI samples, RSV prevalence was 16.1% (739/4604), predominantly pediatric (88.6%, p < 0.001), with peak burden in infants <6 months (70.4% of cases, p < 0.001). Pediatric prevalence was 28.3% (655/2316) vs. 3.8% (84/2204) in adults (p < 0.001), with predominance in the elderly ≥60 years (51/1041, 4.9%). Co-infections occurred in 46.7% (310/665) of FilmArray-tested positives (total = 665), led by rhinovirus/enterovirus (198/310, 63.9%), and were significantly higher in children (48.5%, p < 0.001). RSV peaked in winter (51.6%), except for summer dominance in 2021 (52.5%), reflecting COVID-19 non-pharmaceutical intervention effects. Conclusions: These data establish Morocco’s first comprehensive RSV surveillance baseline, highlighting post-pandemic epidemiological shifts. As maternal vaccines and monoclonal antibodies emerge, these data inform optimal implementation in low- and middle-income countries (LMICs). Full article

The Enzyme-Linked ImmunoSpot (ELISPOT) assay is a highly sensitive and widely used technique for assessing antigen-specific cellular immune responses in cancer research. By enabling the quantification of cytokine secretion at the single-cell level, particularly interferon gamma (IFN-γ), ELISPOT provides a functional readout of T cell activity with applications in both preclinical and clinical settings. This systematic review presents a structured qualitative synthesis of 78 studies investigating the use of ELISPOT in cancer immunotherapy, including cancer vaccines, oncolytic viruses, cellular therapies, immune checkpoint inhibitors, and biomarker development. Studies were selected following PRISMA guidelines from PubMed, Scopus, and Embase, focusing on both clinical and preclinical research with translational relevance. The evidence indicates that ELISPOT is widely used to validate tumor-associated antigens and neoantigens, monitor antigen-specific T cell responses during cancer immunotherapy, including immune checkpoint blockade, cancer vaccines, and adoptive cell therapies, and characterize antigen-specific T cell function. However, only a limited subset of studies establishes direct associations between ELISPOT responses and clinically meaningful outcomes. In addition, substantial variability in assay protocols and reporting criteria limits cross-study comparability and reproducibility. Overall, ELISPOT remains a valuable tool for immune monitoring in cancer research. Still, its implementation as a clinically validated biomarker requires further standardization, prospective validation, and integration with complementary analytical approaches. Full article

Background: Despite the availability of safe vaccines, Ethiopia’s human papillomavirus (HPV) vaccine uptake remains suboptimal, particularly among out-of-school girls (OOSGs). This study examines the effect of multi-channel demand generation messages in two districts to determine which interventions most effectively improve uptake. Methods: A convergent mixed-methods design was employed across four districts in the Somali and South Ethiopia regions, with Jigjiga and Derashe serving as intervention sites and Gode and Kolango Zuria as controls. For the quantitative component, 950 sample households were recruited using cluster sampling. The qualitative inquiry involved 27 in-depth interviews (IDIs) and 16 focus group discussions (FGDs) within the intervention sites. Results: A total of 950 caregivers and 1134 girls completed the survey. Awareness was significantly higher among caregivers (AOR: 4.42; 95% CI: (3.06, 6.39)) and girls (AOR: 7.63; 95% CI: (3.49, 16.67)) in intervention sites, as well as among in-school girls (AOR: 13.46; 95% CI: (4.09, 41.90)). The mean vaccination coverage reached 71%, with significantly higher rates in intervention sites (AOR: 4.07; 95% CI: (2.29, 7.23)) and among in-school girls (AOR: 47.16; 95% CI: (20.23, 109.9)). Interpersonal communication—via teachers, peers, community health workers and vehicle-mounted promotion—was more effective in influencing awareness, attitude and uptake. Barriers for OOSGs included limited access to vaccination sites, low campaign awareness, misconceptions and gender-related issues. Conclusions: Appropriate demand generation strategies effectively enhance HPV awareness and vaccine uptake, yet a significant equity gap remains, as only one-third of OOSGs received the vaccine compared with 85% of in-school girls. Targeted interventions are recommended for OOSGs focused on both access to service and context-specific demand creation to address this disparity. Full article

Hepatitis B virus (HBV) remains a leading cause of chronic liver disease worldwide, contributing to cirrhosis and hepatocellular carcinoma. Sub-Saharan Africa accounts for an estimated 68% of incident HBV infections, where co-infection with human immunodeficiency virus (HIV) is common and associated with poorer clinical outcomes. In Botswana, limited HBV screening and the absence of established HBV management guidelines persist despite reported HIV-HBV co-infection rates ranging from 1.1% to 10.6%. This scoping review aimed to summarise existing research on HBV and HIV-HBV co-infection in Botswana and assess clinical and policy implications. Following PRISMA methodology, searches were conducted across PubMed, Google Scholar, Semantic Scholar, and Consensus databases. Thirty eligible peer-reviewed studies were identified and evaluated for prevalence data, virological characteristics, genotypes, mutations, treatment outcomes, vaccination programs, and the availability of guidelines. Findings indicate intermediate-to-high HBV and HIV-HBV disease burden, substantial occult HBV infection, and gaps in diagnostic and preventive practices. The lack of routine screening, deficient infant birth-dose and adult vaccination, and established treatment pathways likely increase the risk of HBV-associated morbidity and mortality. Strengthened public health interventions, including expanded testing, enhanced vaccination coverage, and prevention of mother-to-child transmission strategies, are recommended to improve disease control and clinical outcomes in Botswana. Full article

Yellow fever (YF) is an infectious disease caused by the yellow fever virus (YFV), an arbovirus of the Flaviviridae family. It is transmitted through the bite of infected mosquitoes of the Culicidae family and affects both humans and non-human primates (NHPs). This study aimed to investigate the sylvatic Culicidae fauna and the occurrence of natural YFV infection in a microregion of southern Santa Catarina, Brazil, an area recently affected by a sylvatic YF outbreak. Entomological collections were conducted between January and February 2023 in five municipalities with confirmed viral circulation. Natural YFV infection was assessed using RT-LAMP. A total of 4352 female culicids were collected, representing at least 32 species, including several key sylvatic YFV vectors. Haemagogus leucocelaenus was identified in all sampled municipalities, whereas Haemagogus (Haemagogus) janthinomys Dyar, 1921, historically considered the primary vector of sylvatic YFV in Brazil, was not detected. Mosquitoes from the genera Aedes Meigen, 1818; Haemagogus Williston, 1896; Psorophora Robineau-Desvoidy, 1827; and Sabethes Robineau-Desvoidy, 1827 were tested for YFV. Only one pool, composed of Sabethes albiprivus, tested positive, yielding a minimum infection rate (MIR) of 11.6. This is the first record of natural YFV infection in Sa. albiprivus in southern Brazil, and only the third record globally, highlighting its potential role as a secondary vector in maintaining viral circulation in sylvatic environments. Based on species presence and abundance, Hg. leucocelaenus is likely to have acted as the primary YFV vector in the study area. The composition of the culicid fauna, coupled with the detection of YFV in sylvatic vectors, indicates an ongoing epidemiological risk. These findings underscore the need to strengthen entomological surveillance and expand YF vaccination coverage in affected and neighbouring regions. Full article

Glioblastoma (GB) remains the most aggressive primary brain malignancy, with the Stupp regimen persisting as the standard of care for nearly two decades despite poor survival outcomes. This review was synthesized by extensively reviewing and analyzing the literature from PubMed, Scopus, and Web of Science to evaluate the emerging promising therapeutic and diagnostic strategies for combating GB. Results indicate significant progress in molecularly targeted therapies, biomimetic nanocarriers, and advanced radiotherapy. While immunotherapeutic approaches, such as checkpoint inhibitors and vaccines, show variable clinical success, the integration of bioinformatics and machine learning has significantly enhanced treatment response prediction. Furthermore, advances in radiomics and molecular imaging have improved the differentiation between true tumor progression and pseudoprogression, potentially reducing invasive diagnostic requirements. Additionally, other emerging and investigational adjuvant therapeutic approaches have shown promise. We conclude that, while multimodal strategies integrating molecular and computational approaches offer a path toward personalized GB management, significant barriers—namely tumor heterogeneity and the blood–brain barrier—persist. Future research must prioritize precision-based combinatorial models to successfully translate these preclinical advancements into improved clinical outcomes for patients. Full article

Background and Clinical Significance: Osmotic demyelination syndrome (ODS) and pituitary apoplexy are rare but potentially severe neurological and endocrine complications that can arise in the context of profound metabolic stress. Case Presentation: We describe the case of a previously healthy 34-year-old man who developed severe symptomatic hyponatremia shortly after receiving his second dose of an mRNA COVID-19 vaccine. Initial laboratory findings and clinical assessment were consistent with syndrome of inappropriate antidiuretic hormone secretion. Following correction of serum sodium, the patient experienced neurological deterioration with gait disturbance, dysarthria, and cognitive impairment. Follow-up brain MRI demonstrated extrapontine osmotic demyelination involving the basal ganglia and thalamus, despite initially normal imaging. During subsequent endocrinological follow-up, pituitary MRI revealed pituitary apoplexy in a previously unrecognized adenoma, accompanied by evolving partial hypopituitarism. The patient was managed with careful electrolyte control and long-term hormone replacement therapy, including hydrocortisone, levothyroxine, and recombinant growth hormone, resulting in gradual functional and cognitive improvement. Conclusions: This case highlights the interaction between severe hyponatremia, osmotic stress, and pituitary vulnerability, and emphasizes the need for cautious sodium correction, careful interpretation of temporal associations, and continued clinical vigilance in the context of COVID-19 vaccination programs. Full article

Background/Objectives: This article reports results from a multisite field trial conducted as part of the regulatory evaluation of a novel monovalent vaccine for Atlantic salmon targeting an emerging variant of Moritella viscosa, with the objective of assessing safety and performance under commercial production conditions. Methods: The trial included approximately 8 million Atlantic salmon reared at seven freshwater and eleven seawater sites in Norway. At each site, fish in the test and control groups received identical vaccination regimens, with the test group additionally receiving the test vaccine. Fish were monitored from vaccination until harvest. Safety endpoints included post-vaccination mortality and local reactions; effectiveness endpoints included outbreak-related mortality and antibody responses. Harvest quality was evaluated as an exploratory endpoint. Results: Post-vaccination mortality within 21 days was low and comparable between groups. Local reaction scores were within acceptable ranges but slightly higher for the test group. Outbreaks of winter ulcer disease caused by variant M. viscosa occurred at three seawater sites, during which test groups were associated with substantially lower mortality compared with controls. At these sites, the proportion of downgraded fish at slaughter was consistently lower in test than control groups. Across sampling points, the test group showed higher antibody titers than the control group. Conclusions: Co-administration of the monovalent variant M. viscosa vaccine with commercial core vaccines was associated with reduced disease burden during outbreaks and a favourable safety profile under commercial farming conditions. These findings support its potential relevance in vaccination programmes for Atlantic salmon farming. Full article

Dendritic cells (DCs) are central to cancer immunity, orchestrating both innate and adaptive immune responses. In melanoma and other solid tumors, however, their function is often impaired within the tumor microenvironment (TME), leading to weakened antitumor immunity and diminished responses to immune checkpoint inhibitors (ICIs) and adoptive tumor-infiltrating lymphocyte (TIL) therapy. Among the various cell-based immunotherapy approaches, DC therapy—particularly using blood-derived conventional DCs (cDCs)—holds considerable promise. Compared with traditional monocyte-derived DCs (moDCs), cDCs exhibit superior antigen processing and cross-presentation capacities. The therapeutic application of cDCs was initially pioneered in vaccine strategies involving ex vivo antigen loading and maturation, followed by administration to lymph nodes. More recently, intratumoral (IT) cDC immunotherapy has emerged as a strategy to reinvigorate the cancer-immunity cycle by engaging the full repertoire of tumor-associated antigens while limiting systemic toxicity. This review discusses the underlying biological mechanisms and summarizes the clinical outcomes of IT DC therapy in cancer. Notably, combination approaches incorporating IT cDCs with ICIs, oncolytic viruses, synthetic adjuvants, radiation, or cryotherapy are emerging as promising strategies to overcome both primary and acquired resistance to ICI monotherapy. Collectively, these findings highlight the potential of integrating IT cDC therapy with complementary immunotherapies in next-generation, cross-tumor treatment strategies. Full article

Background: In this study, we evaluated the effects of the nonavalent Gardasil^® vaccine in a heterogeneous cohort of women who underwent conization or LLETZ for various degrees of CIN, aiming to assess the adjuvant effect of vaccination on HPV clearance. Methods: We conducted a three-year prospective study with a two-year follow-up of 219 patients presenting to our facility for cervical dysplasia. All patients underwent HPV genotyping and were divided into HPV-vaccinated and non-vaccinated groups. Results: We detected a significant association between the final outcome and vaccination timing (p-value = 0.005). All women vaccinated before conization achieved viral clearance; 94.9% of those vaccinated at the time of conization/LLETZ and 68.6% of those vaccinated after the excisional procedure became HPV-negative. Logistic regression showed that, with increasing age, the likelihood of healing after vaccination decreased by approximately 9% per additional year, and non-16/18 HPV-positive women had a 5.5-fold higher chance of healing after vaccination compared with those HPV-positive for 16 and 18 genotypes. Conclusions: Adjuvant prophylactic HPV vaccination in the context of surgical treatment for cervical precancerous lesions is significantly associated with a reduced risk of lesion recurrence and HPV persistence/reinfection when administered prior to or at the same time as the excisional procedures. Full article

Background/Objectives: Mechanical ventilation (MV) is a crucial intervention in managing severe respiratory failure due to COVID-19. However, its use may be complicated by pulmonary barotrauma, a serious event associated with increased morbidity and mortality. Understanding its incidence and associated risk factors is essential for optimising ventilatory strategies and improving patient outcomes. The aim of this study was to determine the incidence and risk factors associated with the development of pulmonary barotrauma in mechanically ventilated patients with COVID-19. Methods: All mechanically ventilated patients aged 18 years and above who were admitted to the COVID-19 Intensive Care Unit (ICU) from January 2021 to June 2022 were included. Patients who developed pulmonary barotrauma prior to or within 24 h of ICU admission, had iatrogenic pneumothorax, were readmitted to the ICU, or were ventilated for causes other than COVID-19-related respiratory failure were excluded. Data on patient demographics, vaccination status, ventilator parameters, laboratory findings, and the use of steroid or immunomodulatory therapies were collected and analysed. Univariate and multivariate logistic regression analyses were performed to identify the potential risk factors and clinical outcomes associated with pulmonary barotrauma. Results: The medical records of 204 patients were included. The incidence of pulmonary barotrauma was 22.5%. Lower C-reactive protein (CRP) levels at ICU admission, lower FiO₂ requirements during the first week of MV, a higher positive end-expiratory pressure (PEEP) during the second week, and a prolonged mechanical ventilation duration were significantly associated with pulmonary barotrauma (p = 0.039, 0.049, 0.021, and 0.036, respectively). Patients who developed pulmonary barotrauma experienced longer ICU stays (p = 0.006) and higher all-cause ICU mortality (p = 0.009). Conclusions: Lower CRP levels and a lower FiO₂ requirements, a higher PEEP use, and longer ventilator days were the independent risk factors for pulmonary barotrauma in our study population, leading to a longer ICU stay and higher all-cause ICU mortality. Full article

Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite’s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals—prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis. Full article