Search Results (232)

As a major retrovirus threatening global poultry farming, Avian Leukosis Virus Subgroup J (ALV-J) has expanded its host range since discovery, extending from conventional broilers to layer chickens and native breeds. Its diverse oncogenic manifestations, including myeloid leukemia, hemangiomas, and tumors of immune and visceral organs, have led to increased mortality, reduced productivity, and substantial economic losses in the poultry industry. Based on the current body of literature, this review summarizes and synthesizes advances in the etiological characteristics, infection and pathogenic mechanisms, host resistance, and research progress in prevention and control of ALV-J. Accumulating evidence indicates that viral evolution driven by mutations and recombination—particularly in the env gene and LTR regions—plays a central role in host range expansion, tumor diversity, and immune evasion. Current studies consistently demonstrate that host resistance to ALV-J is a multifactorial process involving genetic polymorphism, innate immune responses, and cellular autonomous defense systems. In this context, recent advances in disease-resistant breeding highlight CRISPR-Cas9-mediated gene editing as a promising strategy for blocking viral entry or replication. Despite these advances, major gaps remain, including an incomplete understanding of virus–host interaction networks, limited insight into co-infection-mediated synergistic pathogenicity, the absence of effective vaccines, and insufficient large-scale epidemiological surveillance and purification systems. Addressing these challenges will be critical for the development of integrated prevention strategies and the sustainable control of ALV-J in poultry production. Full article

Background: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis remains a major public health concern due to its severity, lethality, and long-term sequelae. To address the rise in serogroups W and Y in Spain, the Community of Madrid implemented a catch-up campaign in 2019–2021, targeting adolescents (ages 13–18) alongside routine tetravalent meningococcus vaccine (MenACWY) at age 12. This study evaluated MenACWY catch-up vaccination uptake in routine practice by describing vaccine coverage, temporal trends, and associated factors in adolescents born between 2001 and 2006. Methods: A population-based cross-sectional study was conducted using data from the Community of Madrid’s vaccination registry (SISPAL Vacunas). Vaccination coverage was calculated for adolescents with at least one recorded MenACWY dose from age 10 onwards. Temporal trends were analyzed by birth cohort and calendar time, and multivariable logistic regression models were used to identify factors associated with vaccination uptake. Results: Among 424,059 adolescents, overall vaccination coverage by December 2021 was 63.8%, ranging from 54.4% to 78.2% across birth cohorts. Coverage was highest in the 2006 cohort, likely due to co-administration with the tetanus and diphtheria (Td) booster. A slightly higher uptake was observed among females and adolescents with chronic conditions, while foreign-born adolescents consistently showed lower coverage. COVID-19 disruptions led to temporal variability, with sharp declines during lockdowns and partial recoveries thereafter, with persistent sociodemographic differences in uptake. Conclusions: By December 2021, coverage was incomplete, with marked variability across birth cohorts. Higher uptake was observed when vaccination was integrated into routine visits, while persistent sociodemographic disparities remained evident. These observational findings are consistent with the programmatic value of combined catch-up and routine strategies and the need for targeted actions to ensure equitable MenACWY coverage. Full article

RNA viruses pose a persistent global threat due to their high mutation rates, zoonotic potential, and rapid adaptability. Emergence events have risen steadily, as demonstrated by major outbreaks caused by Influenza A, Ebola, Zika, and Chikungunya viruses, followed by the coronavirus epidemics of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-1) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and culminating in the COVID-19 pandemic. These characteristics frequently compromise the durability of existing vaccines and antiviral therapies, highlighting the urgent need for new antiviral agents. Alkaloids, a structurally diverse class of nitrogen-containing natural compounds, have gained attention for their ability to interfere with multiple stages of the viral life cycle, including entry, replication, protein synthesis, and host immune modulation. To our knowledge, this review compiles all currently reported alkaloids with antiviral activity against RNA viruses and summarizes their proposed mechanisms of action, distinguishing evidence from in vitro, in vivo, and in silico studies. Quaternary alkaloids are discussed separately because their permanent ionic charge enables distinctive interactions with membranes and host pathways. Although many findings are promising, clinical translation remains limited by incomplete mechanistic validation, scarce in vivo data, suboptimal bioavailability, narrow therapeutic windows, and inconsistent experimental methodologies. To advance the field, future research should prioritize RT-qPCR–based antiviral evaluation to accurately quantify viral replication, incorporate mechanistic assays to clarify modes of action, apply structure–activity relationship (SAR) approaches for rational optimization, and expand in vivo pharmacokinetic and efficacy studies to assess therapeutic feasibility. Overall, alkaloids represent a promising yet underdeveloped reservoir for next-generation antiviral discovery against rapidly evolving RNA viruses. Full article

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) are pediatric inflammatory conditions with overlapping mucocutaneous features that may complicate early diagnosis. We performed a narrative review of the literature to characterize and compare cutaneous manifestations reported in children with KD and MIS-C and to assess their diagnostic relevance. Published studies describing dermatologic findings in patients aged 0–18 years were reviewed. The analysis revealed a broad heterogeneity of skin manifestations in both conditions, ranging from classic polymorphous rash and acral erythema to atypical presentations, including annular, psoriasiform, vesiculobullous, urticarial, and erythema nodosum-like lesions. Reactivation at Bacillus Calmette–Guérin vaccination sites and associated mucocutaneous findings, such as conjunctivitis and oral changes, emerged as supportive diagnostic clues, particularly for incomplete KD. Considerable overlap in cutaneous phenotypes between KD and MIS-C was observed, especially in patients with persistent fever and systemic inflammation, highlighting the risk of diagnostic delay. These findings underscore the importance of recognizing atypical dermatologic patterns as part of an integrated diagnostic approach, as delayed identification may increase the risk of cardiovascular complications. Early recognition of cutaneous clues can support timely initiation of immunomodulatory therapy and improve clinical outcomes. Full article

Oocysts of Toxoplasma gondii exhibit remarkable resistance to environmental stressors and most conventional disinfectants. Despite its ability to infect a wide variety of host species, sexual reproduction and oocyst formation occur exclusively within felid definitive hosts. Despite the epidemiological significance of oocyst-mediated transmission, the molecular mechanisms governing oocyst production and sporulation remain incompletely understood. Glutaredoxin, serving as a central regulator of cellular redox homeostasis and multiple vital cellular processes in cells, is a potential regulator for oocyst sporulation. Here, we investigated the role of TGME49_227100 (glutaredoxin 5, Grx5) in the T. gondii Pru strain-a type II strain capable of oocyst formation, with a particular focus on its functions during oocyst formation and sporulation. We found that Grx5-knockout tachyzoites exhibited no defects in growth or virulence. Neither in vitro nor in vivo tachyzoite-to-bradyzoite differentiation was affected compared to wild-type parasites. Notably, Grx5 deletion significantly reduced oocyst production in cats by approximately 70%. Additionally, the collected oocysts showed a 50% decrease in sporulation rate. These results indicate that Grx5 plays a predominant role within feline host and the external environmental stage of sporulation, which of these is likely to provide a crucial molecular target for developing a transmission-blocking vaccine. Full article

Background: Persistent infection with high-risk human papillomavirus (HPV) is the key driver of cervical carcinogenesis and post-treatment recurrence. Although excisional treatment effectively removes dysplastic tissue, it does not directly target viral persistence. While HPV vaccination is well established in primary prevention, its potential role as an adjuvant strategy in HPV-positive women, particularly with respect to viral clearance, remains incompletely defined. Methods: This retrospective cohort study included HPV-positive women with at least 12 months of follow-up who were managed at a tertiary gynecology clinic. Patients were stratified according to HPV vaccination status with the nonavalent vaccine (Gardasil 9) and excisional treatment status with loop electrosurgical excision procedure (LEEP). HPV clearance at 12 months was defined as the primary outcome, while histological outcomes were evaluated as secondary and independent endpoints. Analyses were performed in the overall cohort and stratified by LEEP status. Multivariable logistic regression was used to identify factors independently associated with HPV persistence, adjusting for baseline disease severity and clinical covariates. Results: A total of 935 HPV-positive women were included in the final analysis. Completion of the three-dose HPV vaccination schedule was associated with significantly higher HPV clearance rates at 12 months compared with no vaccination. This association was consistently observed in women who underwent LEEP as well as in those managed without excisional treatment. In multivariable analysis, HPV vaccination emerged as an independent protective factor against HPV persistence, whereas LEEP status itself was not independently associated with viral clearance after adjustment for baseline histological severity. Histological outcomes differed according to baseline disease severity and did not demonstrate a direct one-to-one relationship with HPV clearance. Conclusions: Adjuvant vaccination with the nonavalent HPV vaccine is independently associated with increased HPV clearance in HPV-positive women at 1-year follow-up, irrespective of excisional treatment status. HPV clearance and histological regression represent related but distinct biological processes and should be evaluated as independent outcomes. These findings support a broader role for HPV vaccination beyond primary prevention and suggest potential clinical benefit of vaccination as an adjunctive strategy in the management of HPV-positive women. Full article

Monkeypox virus (MPXV) is a zoonotic Orthopoxvirus responsible for Monkeypox (Mpox), historically associated with sporadic zoonotic transmission but increasingly characterised by sustained human-to-human spread. While vaccinia-based vaccination is known to confer cross-protection against MPXV, the durability of such immunity over a human lifetime remains incompletely characterised. Here, we assessed humoral and cellular immune responses to MPXV in octogenarians and nonagenarians vaccinated against smallpox during childhood. Twenty-three adults aged 79–94 years (median 83), who self-reported childhood vaccinia vaccination between 1925 and 1940, were recruited. MPXV-specific antibody responses were evaluated using ELISA, targeting homologous vaccinia and MPXV proteins, and live-virus neutralisation assays. Cellular immunity was assessed by IFN-γ ELISpot following stimulation with peptide pools derived from highly conserved vaccinia antigens. Responses were also obtained from younger, recently MVA–BN-vaccinated and unvaccinated control donors. All historically vaccinated participants exhibited MPXV-reactive IgG responses, with antibody binding and neutralisation levels comparable to recently vaccinated individuals. Functional neutralising activity against MPXV was detected in all donors, with ≥50% neutralisation observed in 78% of participants. Antibody concentrations correlated strongly with neutralisation capacity. T-cell responses were detectable in all historically vaccinated donors, most prominently against the major core protein A10L, although reduced magnitudes were observed in participants over 90 years of age. No MPXV-specific humoral or cellular responses were detected in unvaccinated controls. These findings demonstrate that childhood vaccinia vaccination induces durable humoral and cellular immunity against MPXV persisting for over seven decades. Historical smallpox vaccination status may therefore remain a relevant determinant of protection against Mpox. Full article

Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of this study were to estimate the prevalence of complete HPV vaccination and to identify factors associated with vaccination completion among MSM using PrEP in Brazil. Methods: We conducted a cross-sectional online survey between May and September 2025 among MSM aged ≥18 years, residing in Brazil and currently using oral PrEP. Participants were recruited through virtual snowball sampling and targeted advertisements on social media and a gay geosocial networking application. Data were collected using a structured, self-administered questionnaire hosted on REDCap^®. Complete HPV vaccination was defined as self-reported receipt of all doses recommended according to the participant’s age and clinical condition. Sociodemographic characteristics, relationship patterns, sexual behaviors, lubricant use during sexual activity, and history of sexually transmitted infections (STIs) were assessed. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95% CIs) were estimated using Poisson regression with robust (sandwich) variance. Results: A total of 872 MSM using PrEP were included, of whom 59.4% reported complete HPV vaccination. In adjusted analyses, complete vaccination was more frequent among participants reporting both steady and casual partners (aPR = 1.90; 95% CI: 1.36–2.65) or only casual partners (aPR = 1.72; 95% CI: 1.24–2.39), those reporting lubricant use during sexual activity (aPR = 1.41; 95% CI: 1.23–1.61), and those with a diagnosis of chlamydia and/or gonorrhea in the previous 12 months (aPR = 1.22; 95% CI: 1.08–1.36). Conclusions: Although HPV vaccination coverage among MSM using PrEP in Brazil is higher than that reported for MSM in general, it remains incomplete in a population with regular contact with specialized health services. Integrating systematic assessment and delivery of HPV vaccination into PrEP care may help increase vaccination completion and reduce missed opportunities for prevention. Full article

The endemicity of H9N2 avian influenza viruses (AIVs), particularly the Y280 lineage, poses persistent challenges to the poultry industry due to the limitations of inactivated vaccines, such as interference by maternally derived antibodies (MDAs) and incomplete suppression of viral replication. This study evaluated the immunogenicity and protective efficacy of a novel recombinant turkey herpesvirus vaccine expressing the hemagglutinin gene of H9N2/Y280 (rHVT-H9/Y280) in commercial Hy-Line Brown layers with high-MDA backgrounds. In a comparative challenge study, the rHVT-H9/Y280 vaccine induced complete protection against a homologous Y280 strain challenge at 4 weeks of age, whereas commercial inactivated vaccines failed to completely block replication, showing virus isolation rates of 16.7–25%. Long-term serological monitoring demonstrated that the rHVT-H9/Y280 vaccine elicited a robust humoral response characterized by persistent maintenance of high HI titers (>8.0 log₂) up to 39 weeks post-vaccination. These findings confirm that rHVT-H9/Y280 effectively overcomes MDA interference and provides protection by inhibition of viral replication in layer chickens, making it a promising candidate for the effective control of H9N2 AIV in endemic regions. Full article

Cutaneous squamous cell carcinoma (cSCC) is an immunogenic malignancy with variable immune infiltration and inconsistent responses to checkpoint blockade. Tumor-infiltrating lymphocytes (TILs) influence tumor progression and therapeutic outcome, yet their phenotypic and functional diversity across disease contexts remains incompletely understood. This review systematically characterizes the TIL landscape in human cSCC. Following PRISMA 2020 guidelines, PubMed and Embase were searched up to May 2025 and restricted to studies evaluating tumor-infiltrating lymphocytes in human cSCC, using the modified Newcatle–Ottawa score to assess risk of bias. Data were synthesized qualitatively given methodological heterogeneity. 48 studies met inclusion criteria. cSCCs exhibited dense CD3⁺ infiltrates composed of cytotoxic (CD8⁺GzmB⁺, Ki-67⁺, CD69⁺) and regulatory (FOXP3⁺, CCR4⁺) subsets. Higher CD8⁺ activity correlated with smaller tumors and longer disease-free survival, whereas FOXP3⁺ enrichment and TGF-β2 signaling promoted immune evasion. Immunosuppressed patients demonstrated diminished CD8⁺ density and clonality. Immune modulation with PD-1/PD-L1 blockade, imiquimod, HPV vaccination, or OX40 stimulation enhanced effector function. The cSCC immune microenvironment reflects a balance between cytotoxic and suppressive factors. Harmonizing multimodal immune profiling and integrating spatial context with systemic immune status may advance both prognostic stratification and therapeutic design. Full article

Arthropod-borne orthoflaviviruses, including dengue, Zika, Japanese encephalitis, yellow fever and West Nile viruses, pose a significant global public health threat, causing hundreds of millions of infections annually with severe clinical symptoms. However, the lack of effective vaccines and antiviral drugs, coupled with the biosafety risks associated with handling live highly pathogenic strains, hinders progress in antiviral research. Pseudovirus technology, which uses single-round infectious viral particles lacking replication competence, has thus gained prominence as a safe and versatile tool for antiviral research. This review systematically summarizes the construction, optimization, and applications of orthoflavivirus pseudoviruses in antiviral research. The primary construction strategies of orthoflavivirus pseudoviruses rely on multi-plasmid co-transfection of viral replicons and structural protein expression vectors, leveraging the host cell secretory pathway to mimic natural viral assembly and maturation. The core applications of pseudovirus technology are highlighted, including high-throughput screening and detection of neutralizing antibodies, identification of antiviral drugs targeting viral entry or replication, and evaluation of vaccine immunogenicity. Despite these strengths, the approach still faces limitations, such as incomplete simulation of native viral structures and batch-to-batch titer variability, which may affect the physiological relevance of findings. In summary, orthoflavivirus pseudovirus technology has become an essential platform in both basic virology research and translational medicine, providing critical insights and tools in the ongoing fight against arthropod-borne orthoflaviviruses diseases. Full article

Background/Objectives: Vaccination programs are highly effective public health interventions, yet parental hesitancy toward combination vaccines has led to growing demand for alternative vaccination schedules, defined in this study as parental requests to split or replace recommended combination vaccines with single-antigen vaccines for non-clinical reasons. While parental attitudes have been widely studied, little empirical evidence exists on the real-world use of single-antigen vaccines and their public health implications in countries with otherwise high coverage. This study examined the prevalence patterns and parental motivations for requesting such alternative vaccination schedules in Israel, where national guidelines recommend specific combination vaccines, including measles-mumps-rubella-varicella (MMRV) and the pentavalent diphtheria-tetanus-pertussis–inactivated polio–Haemophilus influenzae type b (DTaP+IPV+Hib) vaccines, but informal accommodations exist. Methods: A mixed-methods design was employed: a retrospective cohort analysis of vaccination data from 2018 to 2021 (before and during the COVID-19 pandemic) focused on measles (first dose at 12 months) and pertussis (four-dose primary series), followed by semi-structured interviews with Maternal and Child Health clinic providers, policymakers, and parents. Results: Alternative vaccination schedules involving single-antigen measles or pertussis vaccines are occasionally used despite official policy, accounting for less than 1% of vaccinations overall. Outcomes include delayed administration, lower uptake of combination vaccines, and incomplete protection in certain groups. Parents cited safety concerns, fear of immune overload, and mistrust of authorities. These concerns were often amplified by misinformation, while providers described balancing parental preferences with the need for adequate coverage. Conclusions: This study provides new evidence on how vaccine hesitancy translates into service utilization, highlights the tension between individualized parental decision-making and contribution to collective health, and underscores the need for communication, policy strategies and service designs that sustain high coverage while addressing community-specific concerns. Full article

Background: Cutaneous viral infections, defined as viral pathogens that either primarily affect the skin (e.g., herpesviruses, enteroviruses) or frequently produce dermatologic manifestations despite systemic tropism (e.g., HIV, SARS-CoV-2), can trigger systemic inflammatory and neurotropic responses that extend their impact to the nervous system. A growing body of evidence suggests that viruses with dermatologic manifestations may play a significant role in the pathogenesis of neurologic disorders. Summary: Although individual viruses have been studied in isolation, the skin–brain axis in viral infections remains incompletely characterized. This review synthesizes existing knowledge and highlights gaps in understanding the mechanisms linking cutaneous viral infections to neurologic disease. We explore the principal mechanisms linking viral skin infections to central and peripheral nervous system damage, including direct neuroinvasion, immune-mediated injury, and vascular or endothelial dysfunction. Particular attention is given to herpesviruses, retroviruses, enteroviruses, and respiratory viruses, which have been associated with conditions such as dementia, multiple sclerosis, myelopathies, Guillain-Barré syndrome, and the post-acute neurologic sequelae of COVID-19. Furthermore, we discuss the role of neuroinflammation in viral-associated neurodegeneration and highlight emerging evidence supporting the recombinant zoster vaccine (Shingrix) as a potential modulator of neuroinflammatory processes and a protective factor against dementia. Conclusions: Cutaneous viral infections extend beyond local skin pathology, contributing to a broad spectrum of neurologic complications through intertwined infectious and inflammatory mechanisms. A clearer understanding of how peripheral viral activity shapes central nervous system vulnerability remains a major unmet need. A multidisciplinary approach integrating dermatologic and neurologic perspectives is essential for early recognition and prevention. While observational studies suggest that zoster vaccination may reduce viral reactivation and modulate neuroinflammatory pathways, definitive evidence of neuroprotection is still lacking. Future studies should clarify causal relationships, test mechanistic hypotheses regarding skin–brain immune crosstalk, and explore vaccine-mediated neuroprotection as a novel therapeutic strategy. Full article

Abortive zoonoses represent a major public-health threat and a significant constraint on small-ruminant production in West Africa, particularly in Benin. Yet they remain largely undocumented from the perspective of frontline actors. This cross-sectional study assessed the levels of knowledge, attitude, and perception (KAP) of Beninese farmers, butchers, meat inspectors, and para-veterinary staff. A structured questionnaire containing 28 items (11 knowledge, 9 attitudes, 8 perception) was administered to four professional groups (small ruminant keeper, para-veterinarian, butcher and meat inspectors) from four communes in the South, Central, and North of Benin. The number of correct and desirable responses was evaluated on a 0–100% scale. Overall, respondents demonstrated limited knowledge (50.4 ± 25.2%), highly undesirable attitudes (71.0 ± 23.2%) (higher attitude score means risky practices), and likely desirable (65.0 ± 24.4%) toward abortive zoonoses. Mixed-effect linear regression revealed that knowledge was generally higher among trained professionals such as meat inspectors and para-veterinarians. On the other hand, farmers and butchers showed larger informational gaps and more frequent risky practices. Respondents with previous experience of livestock abortion tended to be more aware of zoonotic risks but did not consistently translate this awareness into safer behavior. Correlations between knowledge and perception were weak and non-significant (r = 0.14; p = 0.135). Psychometric analysis revealed that the Knowledge scale was robust and effectively discriminated between respondents, while the Attitude scale showed poor validity, likely due to social desirability bias. Most participants perceived abortive diseases as a serious threat, yet this awareness did not translate into safer practices. The findings highlight substantial cognitive gaps, persistent risky practices and an incomplete perception of danger among value-chain actors. They underscore the need for targeted, behavior-change interventions in Benin, prioritizing practical training for farmers and butchers and the scaling-up of flock vaccination within a strengthened One Health framework. Full article

Flavivirus infections, including dengue, Zika, West Nile, and Japanese encephalitis, remain a major global health concern. Although several vaccines are licensed, the durability and qualitative features of vaccine-induced antibodies differ substantially across platforms, leading to incomplete cross-protection and the risk of antibody-dependent enhancement. Long-term durability is exemplified by YF-17D, which induces protective antibodies that have been detectable for decades, whereas the JE SA14-14-2 vaccine has achieved program-level reductions in disease in endemic regions. In contrast, CYD-TDV shows serostatus-dependent outcomes, and the investigational TAK-003 vaccine has demonstrated antibody persistence for at least four years. Recent studies have clarified how preserving quaternary envelope epitopes, minimizing prM-associated non-neutralizing specificity, and sustaining germinal center activity determine antibody affinity, breadth, and persistence. Advances in adjuvant formulations and delivery platforms have shown that engaging defined innate pathways and prolonging antigen availability enhance affinity maturation and long-lived plasma cell formation. Booster scheduling and baseline serostatus further shape the antibody quality, highlighting the importance of immune imprinting and cross-reactivity in vaccine design. Together, these findings outline the design principles for next-generation flavivirus vaccines, including stabilization of neutralization-sensitive epitopes, use of adjuvants that sustain germinal center responses, optimization of antigen persistence, and tailoring of dosing strategies to immune history to elicit durable and broadly protective humoral immunity. Full article