Search Results (24,741)

The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy. This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and A/Guangdong-Maonan/SWL1536/2019 (GD1536, 2009/H1N1). Cross-hemagglutination inhibition (HI) assays revealed a significant antigenic disparity, with a 16-fold reduction in heterologous versus homologous HI titers. Comparative sequence analysis identified 22 amino acid differences across the five major antigenic sites (Sa, Sb, Ca1, Ca2, and Cb) of the HA1 subunit. Using reverse genetics, a panel of mutant viruses was generated. This study revealed that a single histidine (H)-to-asparagine (N) substitution at residue 128 (H3 numbering) in the Sa antigenic site acts as a primary determinant of antigenic variation, sufficient to cause a four-fold change in HI titers and a measurable drift in antigenic distance. Structural modeling via AlphaFold3 and PyMOL software suggests that the H128N mutation may alter the local conformation of the antigenic site. It is plausible that H at position 128 could exert electrostatic repulsion with adjacent amino acids, whereas N might facilitate hydrogen bond formation with neighboring residues. These interactions would potentially lead to structural changes in the antigenic site. Our findings confirm that residue 128 is a critical molecular marker for the antigenic differentiation of EA H1N1 and 2009/H1N1 viruses. The study underscores the necessity of monitoring specific HA mutations that could reduce cross-reactivity and provides valuable insights for refining vaccine strain selection and pandemic preparedness strategies. Full article

Background/Objectives: Precautionary health behaviours (PHBs), such as hand-washing or self-isolation, are non-pharmaceutical interventions used to reduce SARS-CoV-2 transmission. We investigated the potential confounding by PHBs of COVID-19 vaccine effectiveness (VE) estimates in a subset of study participants enrolled in id.DRIVE. Methods: The id.DRIVE COVID-19 VE study (formerly COVIDRIVE) is a European multicentre test-negative case–control study estimating COVID-19 VE against hospitalisation due to laboratory-confirmed SARS-CoV-2 in patients with severe acute respiratory infection. All adults (≥18 y) prospectively enrolled between 16 November 2021 and 16 August 2023 at three sites were invited to complete a PHB survey capturing indicators of PHBs in the 3 months preceding admission. Fisher’s exact test with Bonferroni-adjusted threshold was used to measure the level of association between PHB indicators and both COVID-19 vaccine status and SARS-CoV-2 test result. VE estimates were generated with and without adjustment for PHBs. Results: PHBs were modified over time, with higher precautionary attitudes in the first COVID-19 vaccine booster season (2021–2022) compared to the second one (2022–2023). For the first booster season, PHBs were positively associated with exposures (vaccination status) and outcomes (case or control status). Adjusting for PHBs led to a 6 to 9 percentage-point increase in VE estimates. Conversely, no confounding by PHBs was observed in the second booster season. Conclusions: PHBs should be considered a possible confounder of COVID-19 VE studies. Further research is needed to define when PHBs should be integrated into VE models, as the level of confounding may differ according to the study population and the epidemiological context. Full article

Cancer treatment remains challenging due to the complexity of the tumor microenvironment, which promotes tumor heterogeneity and contributes to the development of multidrug resistance, ultimately hindering drug delivery and reducing therapeutic efficacy. In recent years, biomimetic nanocarriers have emerged as promising tools to address these challenges. Among them, cancer cell membrane (CCM)-coated nanoparticles (CCM-NPs) have attracted increasing attention due to their unique advantages, including homologous targeting, prolonged circulation mediated by self-recognition, and enhanced tumor penetration. Moreover, CCM-NPs can serve as versatile platforms for tumor vaccines by leveraging their inherent tumor-associated antigens and immunomodulatory potential. By leveraging CCMs to functionalize NPs, researchers have developed innovative approaches to improve drug delivery, enhance tumor immunotherapy, and optimize cancer vaccine efficacy. Despite these advancements, a comprehensive review summarizing the latest progress in CCM-based biomimetic nanocarriers for tumor treatment is lacking. This review integrates recent advances in CCM-NPs for targeted drug delivery and cancer vaccination, and discusses their fabrication, characterization, mechanisms and applications across multiple cancer types, which provides timely insights to guide their future development in precision tumor therapy. Full article

Virus-like particles (VLPs) formed as a result of self-assembly of viral capsid proteins are widely used as a platform for antigen presentation in vaccine development. However, since the inclusion of a foreign peptide into the capsid protein can alter its spatial structure and interfere with VLP assembly, such insertions are usually limited to short peptides. In this study, we have demonstrated the potential of capsid protein (CP) of single-stranded RNA phage PQ465 to present long peptides using green fluorescent protein (GFP) as a model. GFP was genetically linked to either the N- or C-terminus of PQ465 CP. Hybrid proteins were expressed in Escherichia coli and Nicotiana benthamiana plants. Spherical virus-like particles (~35 nm according to transmission electron microscopy) were successfully formed by both N- and C-terminal fusions expressed in E. coli, and by plant-produced CP with GFP fused to the C-terminus. ELISA revealed that GFP in VLPs was accessible for specific antibodies suggesting that it is exposed on the surface of PQ465-GFP particles. VLPs carrying GFP were recognized by anti-CP antibodies with less efficiency than VLPs formed by empty CP, which indicates shielding of the CP core in PQ465-GFP particles. Therefore, PQ465 CP can be used as a chimeric VLP platform for the display of relatively large protein antigens, which can operate in bacterial and plant expression systems. Full article

Background and Objectives: Measles is a highly contagious but vaccine-preventable disease with significant morbidity in the European region, including Romania, especially in the post-COVID-19 era with low vaccination rates which no longer provide herd immunity. The current study aims to show how vaccination reduces the disease burden. Methods: A study using 29,148 cases with measles-compatible features in Romania from the 2020–2024 period was performed, analyzing symptoms, complications, and hospitalization rates comparatively between vaccinated and non-vaccinated groups. Results: Our findings show substantial hospitalization rates reduction among vaccinated cases with an over 12% decrease—depending on the number of MMR doses—as well as reduced severity of clinical features, but no significant effect on disease duration. Conclusions: MMR vaccination provides protection beyond primary disease prevention, as it reduces the disease burden among measles cases by reducing disease-related hospitalizations and improving clinical outcomes. Full article

Animal toxins contain various bioactive peptides and proteins which have evolved to interact in specific ways. As such, they are a good starting point for developing new drugs and vaccines. This paper examines three natural neurotoxins derived from the black mamba (Dendroaspis polylepis), which show significant pharmacological potential: mambalgins, fasciculins and dendrotoxins. All three may be of value in the treatment of pain, cancer and neurodegenerative disease. Mambalgins provide similar pain relief to opioids but without the risk of addiction; they act by selectively blocking acid-sensitive ion channels (ASICs), especially ASIC1a. Thanks to this inhibitory activity they also demonstrate selective activity against glioblastoma, melanoma and leukemia cells as innovative anticancer drugs. Fasciculins are very strong inhibitors of acetylcholinesterase (AChE) and hence offer promise in multi-target drugs and as treatments for treating Alzheimer’s disease. Dendrotoxins such as DTX-K and DTX-I are able to modulate neuronal excitability and synaptic transmission by blocking voltage-gated potassium channels (Kv1.1, Kv1.2, Kv1.6); both have been shown to be effective against cancer cells, and to influence the cardiovascular, immune, and digestive systems. Recent advances in recombinant biotechnology and protein engineering have allowed their safe production with increased therapeutic value. The review examines the translational potential of D. polylepis venom proteins and highlights the need for additional preclinical research on bioactive molecules of toxin origin. Full article

Background/Objectives: Bitter Taste Receptors (encoded by TAS2R genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in TAS2R genes or pseudogenes in COVID-19 are limited. This study examined the association between TAS2R SNPs and COVID-19 infection and seroconversion in European individuals participating in the Canadian Longitudinal Study on Aging. Methods: Data from the Genome-wide Genetic Data, Comprehensive Baseline (version 7.0), Follow-up 2 (version 1.1), COVID-19 Questionnaire Study (4-2020 to 12-2020), and COVID-19 Seroprevalence (Antibody) Study (11-2020 to 7-2021) datasets were accessed. Associations of TAS2R SNPS with COVID-19 infection or seroconversion were determined using logistic regression adjusted for sociodemographics, genetic principal components, smoking, vaccine doses, and chronic medical conditions (diabetes, immune-mediated inflammatory diseases (IMIDs), respiratory disease, and cardiovascular disease). Results: In the COVID-19 Questionnaire Study (N = 14,073), the rs117458236 (C) variant in TAS2R20 showed a trend toward an association with COVID-19 infection (OR = 1.95; 95% Confidence Interval (CI): 0.98, 3.51). In the COVID-19 Antibody Study (N = 8313), the rs2234235(G) variant in TAS2R1 was associated with anti-nucleocapsid (OR = 1.55; CI: 1.06, 2.20) and anti-spike response (OR = 0.74; CI: 0.57, 0.98); the rs2234010(A) variant in TAS2R5 was associated with anti-nucleocapsid (OR = 1.56; CI: 1.08, 2.19); and the rs34039200(A) variant in TAS2R62P was associated with anti-spike (OR = 0.86; CI: 0.77, 0.97). In a subgroup analysis, the rs2234235(G) variant in TAS2R1 was associated with a decreased anti-spike response to infection or vaccination in individuals with IMIDs or respiratory disease and an increased risk of SARS-CoV-2 infection. Conclusions: TAS2R variants are associated with COVID-19 infection and vaccine response. These data may inform personalized management and vaccination strategies. Full article

Bovine viral diarrhea virus (BVDV) is an important pathogen in cattle and causes considerable economic losses worldwide. In Argentina, where there is no national control program, BVDV remains endemic. In this retrospective study, the epidemiological, clinical and pathological features of postnatal BVDV-associated diseases in 50 outbreaks in central Argentina (1995–2024) were analyzed. Data were obtained from field reports, necropsies, and virological results (virus isolation, RT-nPCR, immunochromatography). No seasonal pattern was found. Acute infections (AIs) and mucosal disease (MD) occurred with similar frequency. Clinical signs included salivation, weakness, emaciation and diarrhea. The lesions were widespread and involved the gastrointestinal tract, skin, lymphoid tissues and spleen. Although MD cases has more extensive tissue involvement, no significant differences in morbidity, mortality or distribution of lesions were observed between AIs and MD. BVDV-1b was the most frequently detected subtype. These results highlight the challenges of BVDV control in extensive production systems. Strengthening diagnostic surveillance, implementing targeted vaccination and eliminating persistently infected animals are essential to reduce BVDV impact in endemic regions such as Argentina. Full article

Severe acute respiratory syndrome (SARS), caused by the COVID-19 virus, continues to pose a significant public health challenge in Brazil, particularly in 2024, with high mortality rates among vulnerable groups. This study aimed to describe the sociodemographic, clinical and vaccination profiles of SARS cases due to COVID-19 in Brazil in 2024, as well as analysing factors associated with clinical outcomes such as death, admission to the intensive care unit (ICU) and the need for ventilatory support. A total of 30,529 reported cases were analysed. On average, the interval between the last vaccine dose and symptom onset was 30.31 months (SD = 6.77), while the interval between symptom onset and clinical outcome was 13.26 days (SD = 16.55), revealing significant variability. The results showed higher mortality rates among men (23.7%) than women (19.1%) (p < 0.0001). Mortality increased progressively with age, reaching 24.4% in individuals aged 60 years or older, whereas rates were below 2% in children under 10 years of age. The highest proportions of deaths were observed regionally in the Northeast (26.8%) and North (22.6%), in contrast to the Midwest (17.7%) (p < 0.0001). Men were also more likely to require ICU admission (38.1% vs. 33.6%) and ventilation (62.9% vs. 60.5%). A time interval of over 24 months since the last vaccine dose was associated with higher mortality (21.9% vs. 20.6%; p = 0.0005). These results highlight the importance of ongoing surveillance and updating the vaccination schedule, particularly for more vulnerable populations. Full article

Pseudorabies virus (PRV), a major swine pathogen, causes severe neurological, respiratory, and reproductive disorders, resulting in substantial economic losses to the global swine industry. Previous studies have shown that the gD glycoprotein of PRV has an effective protective effect. In this study, we constructed a plasmid DNA vaccine (pVAX1-GD-Fc) encoding a gD protein fused with pig IgG Fc and evaluated the adjuvant effects of porcine cGAS, the universal STING complex mimic (UniSTING), or IFN-α in mice. The mice were immunized three times (days 0, 14, and 21) with pVAX1-GD-Fc in the presence or absence of an adjuvant, followed by lethal challenge with PRV-HLJ8 3 days after the final immunization. The results revealed that the pVAX1-GD-Fc group exhibited 20% mortality (1/5 mice) on day 7 postchallenge, and all adjuvanted groups achieved 100% survival during the 14-day observation period. Flow cytometric analysis of splenocytes one week after the second immunization revealed significantly greater CD8+ T cell proportions in the adjuvant groups than in both the mock and pVAX1-GD-Fc-only control groups (p < 0.01). Furthermore, T cell proliferation assays demonstrated a significantly increased stimulation index in the adjuvant-treated mice, confirming enhanced cellular immunity. These findings demonstrate that cGAS, UniSTING, and IFN-α can serve as effective vaccine adjuvants to rapidly enhance cellular immune responses to PRV, highlighting their potential application in veterinary vaccines. Full article

In July 2024, bluetongue virus serotype 3 (BTV-3) was first detected in southern Belgium, marking the onset of a major epidemic wave. This study documents, for the first time in Belgium, the ability of BTV-3 to cross the placental barrier in cattle, causing abortions and congenital central nervous system malformations. Abortion cases from January to December 2024 were monitored through the national abortion protocol, which mandates reporting and laboratory investigation (i.e., the year of emergence and the three previous years as the baseline data set). Among 5,751 reported abortions, 903 foetuses were tested by PCR, revealing widespread BTV-3 circulation. The first malformed PCR-positive foetus was recorded in mid-August, four weeks after a sharp increase in abortion rates. Lesions such as hydranencephaly were confirmed in PCR-positive foetuses, with a malformation rate of 32.24% in affected herds from weeks 36 to 52 (i.e., 22 times higher than in previous years). Gestational stage analysis indicated that congenital lesions were most frequent following infection between 70 and 130 days of gestation. Based on the observed gross lesions and the timing of abortion, it was deduced that the earliest maternal infections likely occurred in February–March 2024, implying low-level winter BTV-3 circulation before the official detection of the epidemic wave. These findings highlight the epidemiological value of systematic abortion monitoring as an early warning system tool and highlight the inadequacy of relying solely on clinical surveillance in adult ruminants. The abrupt emergence of BTV-3 across the territory without a gradual spatial spread underscores the need for anticipatory control strategies. Strategic, multivalent vaccination campaigns and enhanced abortion surveillance are critical to mitigate similar reproductive and economic losses in future bluetongue outbreaks. Full article

Chronic hepatitis B (CHB) remains a major global health challenge, largely due to the persistence of covalently closed circular DNA (cccDNA) and impaired host immunity. Interferon-α (IFN-α), a key antiviral cytokine, not only directly restricts HBV replication but also orchestrates innate and adaptive immune responses. This review summarizes current advances in IFN-α-mediated immune regulation, highlighting its effects across diverse immune cell populations. Evidence indicates that IFN-α can reprogram immune responses to promote viral clearance, although clinical efficacy is limited by modest response rates and adverse effects. Recent progress in cytokine engineering, subtype research, and rational combination strategies—including nucleo(s/t)ide analogs, RNA interference therapeutics, antisense oligonucleotides, therapeutic vaccines, and beyond—has expanded opportunities to improve treatment outcomes. While challenges remain, these advances lay the foundation for optimizing IFN-α–based interventions and highlight IFN-α as a key driver for innovative therapies aimed at achieving a functional cure of chronic hepatitis B. Full article

Background: EHEC O157:H7 causes severe gastrointestinal illness by first colonizing the large intestine. It intimately attaches to the epithelial lining, orchestrating distinctive “attaching and effacing” lesions that disrupt the host’s cellular landscape. While much is known about the well-established virulence factors, there are much to learn about the surface proteins’ roles in a living host. Methods: This study presents the first in vivo characterisation of the surface proteome, i.e., proteosurfaceome, of Escherichia coli O157:H7 EDL933 during intestinal infection, revealing spatial and temporal adaptations critical for colonisation and survival. Using a murine ileal loop model, surface proteomic profiles were analysed at early (3 h) and late (10 h) infection stages across the ileum and colon. Results: In total, 272 proteins were identified, with only 13 shared across all conditions, reflecting substantial niche-specific adaptations. Gene ontology enrichment analyses highlighted dominant roles in metabolic, cellular, and binding functions, while subcellular localisation prediction uncovered cytoplasmic moonlighting proteins with surface activity. Comparative analyses revealed dynamic changes in protein abundance. Conclusions: These findings indicate a coordinated shift from stress adaptation and virulence to nutrient acquisition and persistence and provide a comprehensive view of EHEC O157:H7 surface proteome dynamics during infection, highlighting key adaptive proteins that may serve as targets for future therapeutic and vaccine strategies. Full article

Chicken infectious anemia virus (CIAV) causes immunosuppression in poultry, leading to substantial global economic losses through both vertical and horizontal transmission. Since 2014, frequent outbreaks have been reported in southern China; however, the epidemiology of CIAV in Guangdong Province remains poorly defined. Between July 2018 and March 2022, we collected 105 tissue samples and 786 serum samples from poultry in nine cities. PCR/qPCR assays targeting the VP1 gene confirmed CIAV infection, and positive tissues inoculated into MSB1 cells yielded four isolates (GDHZ1, GDHZ2, GDJM, GDLF). Phylogenetic analysis demonstrated that GDHZ1, GDJM, and GDLF clustered within clade A1, whereas GDHZ2 belonged to clade A2. All isolates shared glutamine (Q) at position 394, together with virulence-associated amino acid signatures (75V, 89T, 125L, 139K, 141Q, 144E). Serological testing indicated a high prevalence, with 627 of 786 samples positive (79.77%). The relatively low proportion of virus-positive tissues and successful isolations may reflect viral tropism or limitations in detection sensitivity. These findings enhance understanding of CIAV molecular epidemiology in Guangdong and provide evidence to inform surveillance, vaccination strategies, and control measures. Full article

Antimicrobial resistance (AMR) is a growing global threat, exacerbated by the adaptive mechanisms of Gram-negative ESKAPE pathogens, which include biofilm formation and outer membrane vesicle (OMV) production. Biofilms create robust protective barriers that shield bacterial communities from immune responses and antibiotic treatments, while OMVs contribute to both defense and offense by carrying antibiotic-degrading enzymes and delivering virulence factors to host cells. These mechanisms not only enhance bacterial survival but also increase the virulence and persistence of infections, making them a significant concern in clinical settings. This review explores the molecular processes that drive biofilm and OMV formation, emphasizing their critical roles in the development of AMR. By understanding these mechanisms, new therapeutic strategies can be developed to disrupt these defenses, potentially improving the efficacy of existing antibiotics and slowing the spread of resistance. Additionally, the use of OMVs in vaccine development and drug delivery offers promising avenues for future research. Addressing these challenges requires a comprehensive approach, combining advanced research with innovative therapies to combat the escalating threat of AMR and improve patient outcomes. Full article