Search Results (10,899)

Although canine parvovirus (CPV) vaccination has been widely implemented, CPV continues to circulate in dog populations and poses a potential cross-species transmission risk to wildlife, including giant pandas. Recent increases in CPV-2c detection in China highlight the need for molecular surveillance and standardized immunoreagents for diagnosis and epitope mapping. This study aimed to isolate a representative CPV-2c strain from China and develop VP2-targeted nanobody-based recognition molecules to support antigen monitoring and detection optimization. Canine and giant panda samples were collected in Sichuan Province, and CPV was isolated in F81 cells, followed by VP2 gene sequencing and phylogenetic analysis. A secretion expression system in Bacillus subtilis was established to produce VP2-targeting nanobodies, and a canine Fc-fused format of Nb10 (Nb10-Fc) was constructed. Immunoreactivity was evaluated via immunoassays, and structural modeling and molecular docking were performed to predict binding interfaces. The results showed that CPV-2c was the dominant genotype in Sichuan, with CPV L4 being a representative strain that exhibited 100% identity in VP2 with a giant panda-derived CPV-2c strain. Nb10 and Nb10-Fc demonstrated strong reactivity in Western blotting and immunofluorescence assays. The Fc-fusion improved detection sensitivity, offering potential in vivo application benefits. This study provides a standardized VP2-specific nanobody and molecular system for CPV-2c surveillance, antigenic studies, and diagnostic optimization. Full article

The Bacillus Calmette–Guérin (BCG) vaccine, originally developed for tuberculosis (TB) prevention, has recently attracted attention due to its broader immunomodulatory properties. In addition to its role in TB control, BCG induces trained immunity, a process involving epigenetic and metabolic reprogramming of innate immune cells that leads to altered systemic inflammatory responses. Increasing evidence suggests that these long-term immune adaptations may influence the central nervous system by modulating microglial activation and neuroinflammatory pathways implicated in neurodegenerative diseases. In parallel, chronic infections such as TB are associated with persistent systemic inflammation and immune dysregulation, which may contribute to microglial priming and increased vulnerability to neurodegeneration. This narrative review, based on a targeted literature search of PubMed, Scopus, Web of Science, Embase, and relevant preprint servers, synthesizes current evidence on the relationships between BCG vaccination, trained immunity, and neuroimmune interactions. We focus on studies addressing systemic immune reprogramming, microglial responses, and neuroinflammatory mechanisms relevant to neurodegenerative disorders. The available data suggest that BCG-induced immune modulation may exert context-dependent effects on the brain, with potential neuroprotective implications under certain conditions. However, the evidence remains heterogeneous and largely observational, and causality cannot yet be established. Further mechanistic and prospective studies are required to clarify whether BCG-induced trained immunity can modify the risk or progression of age-related neurodegenerative diseases. Full article

Globally, Mycobacterium tuberculosis (Mtb) remains the leading cause of death from a single infectious agent. The only licensed vaccine, Bacillus Calmette–Guérin (BCG), was developed over a century ago and does not provide consistent protection against pulmonary tuberculosis (TB). Efforts to develop more effective vaccines are hindered by an incomplete understanding of the correlates of protection and by the pathogen’s sophisticated immune-evasion strategies. Mtb systematically undermines host defenses, reprograms host cell biology, and interferes with cell–cell communication to establish a permissive niche and sustain chronic infection. An effective vaccine must elicit immune responses capable of overcoming these bacterial strategies across diverse host and pathogen backgrounds. Traditional approaches focused on boosting T cell responses have proven inadequate. In this review, we summarize innate and adaptive immune mechanisms that contain Mtb, examine how bacterial immune subversion and host–pathogen heterogeneity complicate vaccine design, and highlight emerging concepts and strategies to guide TB vaccine development. Full article

Background: Edwardsiella piscicida is a significant intracellular pathogen of channel catfish (Ictalurus punctatus) and a major threat to U.S. aquaculture. A recently developed recombinant attenuated vaccine strain (χ16016) uses arabinose-regulated murA expression to trigger delayed cell wall lysis in vivo, ensuring biological containment while conferring strong protection against virulent challenge. Although its efficacy has been demonstrated, the host immune programs underlying protection remain incompletely defined. Methods: We used RNA sequencing to characterize tissue-specific transcriptomic responses in the intestines and kidneys of channel catfish at 7 days post-vaccination. Fish were vaccinated with χ16016 by either bath immersion or intracoelomic (IC) injection, and differentially expressed genes and enriched immune pathways were analyzed to determine how the vaccine delivery route shapes systemic and mucosal immune responses. Results: Across comparisons, 19,101 differentially expressed genes revealed pronounced route- and tissue-dependent immune remodeling. As aquaculture vaccination strategies increasingly prioritize scalability and practical deployment, understanding how the delivery route shapes immune outcomes is critical. Here, IC vaccination induced broader systemic transcriptional changes, particularly in the intestine, whereas bath immunization elicited a more focused yet coordinated mucosal response. Overall, intestinal tissue exhibited greater transcriptional responsiveness than kidney tissue, underscoring its central role in early vaccine-induced immunity. Functional enrichment analyses identified the activation of innate recognition pathways, MAPK and calcium signaling cascades, complement components, antigen processing machinery, and cell adhesion networks. Notably, bath immunization enriched the intestinal immune network for IgA production pathway, which represents an orthology-based mapping of conserved mucosal immune components, alongside the upregulation of IL-6, CXCL12–CXCR4, integrins (α4β7), MHC class II, complement C3, and polymeric immunoglobulin receptor (pIgR). Given that catfish rely primarily on IgM in mucosal immunity, these findings indicate the induction of IgM-mediated mucosal defense rather than classical mammalian IgA responses. Concurrent complement and scavenger receptor signatures suggest a transition toward efficient opsonophagocytic clearance with controlled inflammation at this subacute stage. Conclusions: This study provides the first systems-level view of host transcriptomic responses to a regulated-lysis E. piscicida vaccine in channel catfish. The findings demonstrate that immersion vaccination, although transcriptionally less expansive than injection, effectively activates coordinated mucosal innate and adaptive immune programs, supporting its practical use as a scalable vaccination strategy for aquaculture. Full article

Type II toxin–antitoxin (TA) systems are significantly expanded in the Mycobacterium tuberculosis complex; however, the functional role of the VapBC40 system in Mycobacterium bovis(M. bovis) pathogenesis remains poorly characterized. This study aimed to investigate the role of VapBC40 in mycobacterial virulence and evaluate its potential as a target for rational vaccine attenuation. We performed evolutionary analysis and yeast two-hybrid assays to characterize VapBC40 system specificity, conducted in vitro macrophage infection models and in vivo murine studies to assess virulence contribution, and evaluated the immunoprotective efficacy of a VapC40 knockout strain. Evolutionary analysis revealed progressive sequence conservation and stringent homologous pairing specificity within the VapBC40 system. The VapC40 toxin correlates with enhanced intracellular bacterial survival, increased host cell death, and more severe pulmonary pathology with systemic dissemination. Based on these findings, we evaluated the vaccine potential of a vapC40 knockout strain. Immunization with this attenuated strain elicited a Th1 cellular immune response, characterized by enhanced IFN-γ production and increased frequency of CD4⁺IFN-γ⁺ T cells. Upon challenge with virulent M. bovis, the knockout strain conferred superior protection compared to the conventional BCG vaccine, significantly reducing lung pathology and restricting extrapulmonary bacterial dissemination. Although the molecular mechanisms underlying VapC40-mediated effects remain to be fully elucidated, our findings suggest an important role of the VapBC40 system in mycobacterial-host interactions and support its potential as a target for next-generation tuberculosis vaccine development. Full article

Brucellosis remains one of the most widespread zoonotic infections worldwide, causing serious veterinary, medical, and socio-economic consequences. The disease, caused by bacteria of the genus Brucella, affects a wide range of domestic and wild animals as well as humans, with global incidence potentially reaching 1.6–2.1 million new cases annually. The most effective approach to combating brucellosis is specific prevention through vaccination. Therefore, we conducted this review to summarize data from existing studies on modern strategies for brucellosis vaccination, types of vaccine platforms, their efficacy, safety, and applicability in veterinary and human medicine. We searched databases including PubMed, Scopus, and Web of Science to identify relevant scientific articles in English published from 1990 to 2025. The aim of this work is to conduct a systematic analysis of modern brucellosis vaccination strategies in livestock and humans, as well as to evaluate the prospects of new vaccine platforms. The review examines live attenuated, inactivated, subunit, vector, and DNA vaccines, as well as their immunological mechanisms of action, advantages, and limitations of application. This information allows for a better understanding of the mechanisms of protective immunity formation and challenges related to DIVA diagnostics (Differentiating Infected from Vaccinated Animals). The “One Health” concept demonstrated the interconnection between human, animal, and environmental factors, emphasizing the need for an interdisciplinary approach to brucellosis monitoring, prevention, and control. Vector vaccines based on influenza virus (Flu-BA), developed in Kazakhstan, have shown high promise, combining immunogenicity, protective efficacy, and a favorable safety profile. Promising directions remain mRNA vaccines, nanoparticles, CRISPR/Cas9 technologies, and mucosal vaccines. Full article

Background: Tuberculosis (TB) remains a major global health challenge, highlighting the urgent need for more effective vaccines. This study aimed to develop an artificial intelligence-guided epitope prediction and prioritization pipeline to identify immunodominant peptides from Mycobacterium tuberculosis (Mtb) and to evaluate the immunogenicity and protective efficacy of the resulting vaccine candidates. Methods: An AI-guided framework was used to predict and prioritize immunodominant Mtb epitopes, leading to the generation of 72 recombinant immunogens. Among these, RI-13, RI-20, and RI-31 were selected as the leading candidates. Their protective efficacy was assessed in a zebrafish TB infection model and in BALB/c mice following DNA vaccination. Humoral and cellular immune responses were further evaluated in C57BL/6 mice. Results: RI-13, RI-20, and RI-31 markedly reduced infection-associated pathology and lowered bacterial burden by up to 1.5 log₁₀ in the zebrafish TB infection model, outperforming benchmark antigen combinations, including the Ag85A plus ESAT6/CFP10 cocktail used in the phase III vaccine candidate GamTBvac. In BALB/c mice, DNA vaccination with each construct reduced pulmonary mycobacterial burden by approximately 0.3 log₁₀ and alleviated lung tissue damage. In addition, all three candidates elicited robust humoral and cellular immune responses, with RI-13 showing the strongest overall immunogenicity and inducing a balanced Th1, Th2, and Th17 response profile in C57BL/6 mice. Conclusions: These findings identify RI-13, derived from Rv1174c, as a promising next-generation TB vaccine candidate. More broadly, this study supports the utility of an AI-guided framework for the rational design and preclinical prioritization of novel TB immunogens. Full article

Background: The recombinant zoster vaccine (RZV) has been shown to reduce the risk of dementia and delay cognitive decline. However, economic evaluations in populations with mild cognitive impairment (MCI), particularly those incorporating cognitive outcomes, remain unavailable. This study evaluated the cost-effectiveness of RZV vaccination at age 50 among Chinese adults with MCI. Methods: A decision tree–Markov model was developed from a societal perspective to assess the lifetime cost-effectiveness of RZV (Shingrix, GSK) in a cohort of 1 million immunocompetent Chinese adults with MCI receiving vaccination at the age of 50. The primary outcome was the incremental cost-effectiveness ratio (ICER), while secondary outcomes included cases averted and the number needed to vaccinate (NNV) to prevent one case of herpes zoster (HZ), postherpetic neuralgia (PHN), and dementia. A willingness-to-pay (WTP) threshold equivalent to the 2024 Chinese gross domestic product (GDP) per capita (13,121 USD) was applied. Sensitivity analyses were conducted to test the robustness of the results. Results: Over a lifetime horizon, RZV vaccination was estimated to avert 54.64% of HZ cases, 97.58% of PHN cases, and 12.28% of dementia cases compared with no vaccination, resulting in an additional 2.23 million quality-adjusted life years (QALYs) gained. The ICER was 4216.99 USD/QALY, remaining well below the WTP threshold. The corresponding NNVs were 6.25 for HZ, 24.03 for PHN, and 280.82 for dementia progression. Conclusions: RZV vaccination is cost-effective for Chinese adults aged 50 years with MCI, providing substantial health gains through reductions in both HZ burden and dementia progression. Full article

Functional antibody-dependent enhancement (ADE) represents a fundamental and context-dependent characteristic of antiviral antibody responses, reflecting the dual capacity of antibodies to mediate both the neutralization and Fc receptor-dependent enhancement of infection. In flavivirus research, this duality complicates the interpretation of conventional serological metrics and limits the reliability of single-parameter correlates of immunity, particularly in populations with complex exposure histories. Over the past decade, functional ADE assays have evolved from specialized mechanistic tools into integrated immune assessment platforms supporting translational immunology, vaccine evaluation, and population-level immune surveillance. These platforms incorporate Fcγ receptor-relevant target cell systems, standardized viral inputs, dilution series-based profiling, quantitative enhancement metrics, and structured quality control frameworks to enable reproducible, comparable, and context-aware functional measurements across cohorts and laboratories. A central concept emerging from these developments is that ADE reflects a dynamic functional immune state rather than an intrinsic property of antibodies or a direct indicator of pathological risk. Accordingly, functional ADE platforms support the contextual interpretation of antibody activity across physiologically relevant conditions, facilitating discrimination between transient functional enhancement and clinically meaningful immunological risk. By integrating functional ADE metrics with serological, cellular, and epidemiological data, these platforms provide a structured framework for interpreting immune profiles in vaccine evaluation, booster strategy design, and population-level risk stratification. This review synthesizes the development, standardization, and global dissemination of functional ADE platforms and discusses key principles governing biological relevance, analytical robustness, and inter-site transferability. Emerging directions integrating functional ADE profiling with systems immunology, immunogenomics, and computational modeling are highlighted as pathways toward predictive, decision-support-oriented frameworks. By positioning ADE platforms as immune assessment infrastructures rather than isolated assays, this review underscores their value for mechanistic inquiry, translational interpretation, and preparedness-oriented responses to emerging viral threats in the absence of definitive correlates of protection. Full article

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

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 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: 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