Search Results (3,310)

Nanodiamonds (NDs) are an innovative material in biomedical applications based on their excellent biocompatibility, nanoscale dimensions, and high surface area. In this study, we evaluated the potential of ND-in-oil emulsion to induce potent antibody responses in animals immunized with cobra venom. NDs demonstrated the capacity to bind complex venom proteins as stable conjugates, well dispersed in aqueous solution. Immunization of mice with cobra venom incorporated with ND-in-oil emulsion adjuvant (ND/venom) elicited strong venom-specific antibody responses with titers comparable to those induced by venom formulation with conventional Freund’s adjuvants (FA/venom). IgG subclass analysis revealed that ND- and FA-based formulations induced a Th2-biased immune response in mice. Moreover, antibodies elicited by ND/venom or FA/venom immunization specifically recognized the epitopes of the lethal component of short-chain neurotoxin and conferred full protection against lethal cobra venom challenge (3LD₅₀). Further, ND/venom hyperimmunization was capable of inducing high levels of neutralizing antibodies in larger animals, rabbits, highlighting the potential for antivenom manufacturing. Notably, there were no obvious lesions at the injection sites of animals that received ND/venom, in contrast to those that received FA/venom. These findings indicated NDs as an effective and safe additive in venom formulation for antivenom production. Full article

The growing threat of multidrug-resistant fungal pathogens, especially Candida auris, has underscored the need for effective antifungal vaccines. This commentary highlights recent advances in peptide-based vaccination using the SNAP (Spontaneous Nanoliposome Antigen Presentation) platform, focusing on the FM-SNAP vaccine, a bivalent liposomal formulation targeting the surface-expressed peptides fructose bisphosphate aldolase (Fba) and methionine synthase (Met6). Compared to earlier constructs such as MP12, FM-SNAP achieves superior immunogenicity and long-lasting protection at lower antigen doses. It elicits balanced Th1/Th2 cytokine responses and demonstrates durable efficacy in both immunocompetent and complement-deficient mouse models. The platform’s compatibility with clinically approved adjuvants (MPLA and QS-21), modular peptide design, and potential for multi-pathogen applications underscores its translational promise. FM-SNAP exemplifies a next-generation vaccine strategy that is both scalable and adaptable for high-risk immunocompromised populations. Full article

Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a particular problem for the pediatric population among whom the highest mortality from the disease is recorded. Several reasons for this phenomenon can be mentioned, but what is particularly important from the microbiological point of view is the correlation of the increased number of pertussis cases with the introduction of a new form of vaccine—the acellular vaccine in place of the whole-cell vaccine. In this review, we summarized the current state of knowledge on potential factors that may contribute to the decline in immunization efficacy against the pathogen. The post-vaccination response profile, symptomatic of vaccination with vaccination-acellular, is characterized by recruitment of Th₂ and Th₁₇ lymphocytes; it has been reported that in the long term, this results in insufficient activation of B cells and low titers of antibodies to key bacterial antigens (hemagglutinin, pertactin). Moreover, the immune response proceeds by bypassing the recruitment of tissue-resident memory T cells, resulting in a lack of protection against colonization of the nasal cavity by the bacterium despite vaccination. The decline in vaccination efficacy should also be attributed to the phenotypic variability of Bordetella. The popularization of the PtxP3 strain, characterized by its ability to incompletely activate immune mechanisms, poses a real threat to public health. The growing resistance of B. pertussis to standardly used antibiotics including macrolides also remains a problem. This makes it difficult to eradicate pathogens from the nasal cavity area and increases the pool of bacterial carriers in the population area. The increasing prevalence of the disease prompts reflection on more effective methods of prevention. Particularly promising in this field seem to be new vaccines, especially mucosally implemented, e.g., intranasal, or developed on the basis of B. pertussis antigens other than those used so far. Full article

Sex and gender play a critical role in allergic diseases, influencing immune response, clinical phenotypes, treatment strategies, outcomes, and health-related quality of life. Despite mounting evidence across multiple studies examining sex/gender differences in a multitude of allergic diseases, most address isolated conditions, not taking into consideration the vast interplay of hormonal, genetic, immunological, and sociocultural factors and their unique consequences for clinicians and researchers. With this position paper, we aim to assess currently available evidence on the sex- and gender-specific characteristics of the most common allergic diseases, providing an overview of present knowledge and future areas of improvement for clinicians and researchers. This position paper was developed by the Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC): a panel of experts who conducted a literature review focusing on sex and gender differences across major allergic diseases. A consensus-based approach was employed to assess the immunological, clinical, and therapeutic implications of available evidence, offering a recommendation for researchers and clinicians alike. Data highlights marked differences driven by sex and gender in disease prevalence, immune pathways, clinical phenotype and severity, as well as therapeutic outcomes. Female patients appear to show a higher prevalence of Th2-driven ailments, autoimmune overlap, and allergic drug reactions, whereas males are more likely to experience fatal anaphylaxis and severe mastocytosis. Sex hormones can modulate multiple immune pathways leading to mast cell activation, antibody production, and cytokine expression, thus contributing to divergent disease trajectories. In conclusion, sex and gender are a key determinant in allergic diseases, and their integration in future research is essential to develop a tailored approach to treatment. Efforts should prioritise the identification of sex- and gender-specific biomarkers, therapeutic strategies, and equitable access to healthcare services. A sex- and gender-aware approach could potentially improve outcomes, optimise treatment strategies, and address current gaps in allergy practice. Full article

Intracellular pathogens such as Neospora caninum, Brucella abortus, and Bovine Viral Diarrhea Virus (BVDV) are major contributors to bovine abortions, yet many cases remain without a definitive etiological diagnosis despite inflammatory evidence. This study aimed to characterize the immune response in bovine fetuses aborted due to these intracellular agents, comparing them with fetuses showing inflammatory lesions of probable infectious origin and with negative controls. We analyzed cytokine expression (IFN-γ, TNFα, IL-4, IL-8, IL-12) and haptoglobin levels in mid- and late-gestation fetuses. Mid-gestation fetuses infected with intracellular agents exhibited elevated IFN-γ and IL-8 expressions, suggesting a Th1-type immune response, while late-gestation fetuses showed decreased of these cytokines, indicating a shift toward a Th2-type response. Probable infectious abortions at late gestation also showed downregulation of IFN-γ. No significant differences were observed in TNF-α and IL-12 expressions. Additionally, haptoglobin levels were lower in mid-gestation infected fetuses compared to controls. These findings highlight gestational age-dependent immune modulation in response to intracellular infections and suggest that other unidentified pathogens may contribute to abortions with inflammatory lesions but no confirmed etiology. This study enhances our understanding of fetal immune responses in bovine abortions and may support improved diagnostic approaches for reproductive losses in cattle. Full article

Leishmaniasis is a parasitic disease caused by Leishmania spp., transmitted by sandflies, and endemic in 98 countries. Leishmania infantum, the main agent of visceral leishmaniasis in Europe, commonly infects both humans and animals, with dogs as the principal domestic reservoir. Clinical manifestations in dogs depend on the host immune response. A robust Th1 response facilitates macrophage activation and parasite control, while persistently elevated TNF-α and IL-6 can lead to chronic inflammation and tissue damage. Current treatments reduce parasite load but rarely achieve complete cure and are often associated with relapses and resistance. Artemisia annua, source of artemisinin, could be a promising alternative to canine leishmaniasis. Despite its potential, no published studies have investigated its effect specifically against Leishmania infantum as well as its possible dual action: antiparasitic and immunomodulation. We conducted in vitro evaluations of a standardized Artemisia annua extract. Leishmanicidal activity was assessed against both promastigote and amastigote stages, and cytokine modulation was evaluated in RAW 264.7 macrophages. The extract showed strong leishmanicidal activity without cytotoxicity and significantly reduced TNF-α and IL-6 levels under inflammatory conditions, and in both cases, efficiency was correlated with artemisinin content. These results support Artemisia annua as a promising safer therapeutic adjuvant candidate for canine leishmaniasis, targeting both the parasite and the host inflammatory response. Full article

Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4⁺ Th1 and CD8⁺ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8⁺ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin’s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases. Full article

Facial recognition systems are increasingly used for authentication across domains such as finance, e-commerce, and public services, but their growing adoption raises significant concerns about spoofing attacks enabled by printed photos, replayed videos, or AI-generated deepfakes. To address this gap, we introduce a multi-layered Face Recognition-as-a-Service (FRaaS) platform that integrates passive liveness detection with active challenge–response mechanisms, thereby defending against both low-effort and sophisticated presentation attacks. The platform is designed as a scalable cloud-based solution, complemented by an open-source SDK for seamless third-party integration, and guided by ethical AI principles of fairness, transparency, and privacy. A comprehensive evaluation validates the system’s logic and implementation: (i) Frontend audits using Lighthouse consistently scored above 96% in performance, accessibility, and best practices; (ii) SDK testing achieved over 91% code coverage with reliable OAuth flow and error resilience; (iii) Passive liveness layer employed the DeepPixBiS model, which achieves an Average Classification Error Rate (ACER) of 0.4 on the OULU–NPU benchmark, outperforming prior state-of-the-art methods; and (iv) Load simulations confirmed high throughput (276 req/s), low latency (95th percentile at 1.51 ms), and zero error rates. Together, these results demonstrate that the proposed platform is robust, scalable, and trustworthy for security-critical applications. Full article

Background: Gastrointestinal (GI) disturbances occur frequently in the early premotor stage of Parkinson’s disease (PD). These GI impairments are associated, at least in part, with dopaminergic dysfunction in the myenteric plexus. However, the enteric nervous system (ENS) pathophysiology underlying GI dysfunction in PD has been overlooked. Objectives: The aim of this study was to evaluate the premotor GI disturbances in rats submitted to intranasal (i.n.) MPTP, a valid experimental model of the premotor stage of PD. Methods: Ileum segments from male Wistar rats (21 weeks old) were collected 12 days following the i.n. MPTP administration for functional studies. Isometric contractile concentration–response (CR) curves (cumulative) for dopamine (DA) were performed in both the presence and absence of sulpiride, a selective dopamine D2-like receptor (D2R) antagonist. Results: Functional studies showed that DA induced a concentration-dependent contractile response in the ileum, which exhibited marked contraction at lower concentrations (0.01–0.9 µM) and relaxation at higher concentrations (3–90 µM). MPTP significantly attenuated both the contraction and the ensuing relaxation. Furthermore, sulpiride significantly reduced the contractile response to DA in the control group and blocked the relaxation in the MPTP group. The MPTP-induced dysmotility occurred with preserved DA homeostasis, as shown by normal DA, TH, and D2R ileal levels in the MPTP group. However, MPTP seemed to impose a decrease in S100β and GFAP (enteroglial markers) immunostaining in the ileal myenteric plexus. Conclusions: In summary, we provide pioneering functional, neurochemical, and morphological evidence showing that rats submitted to the i.n. MPTP model exhibited premotor DA-dependent ileum motile dysfunction accompanied by enteroglial disturbance within the myenteric plexus, but with preserved DA markers. Full article

Global warming has been altering the East Asian climate at an unprecedented rate since the 20th century. In order to evaluate the changes in the East Asian winter climate (EAWC) and support policy-making for climate mitigation and adaptation strategies, this paper utilizes the multimodel ensemble from the Couple Model Intercomparison Project 6 and a temperature threshold method to investigate the EAWC changes during the period 1979–2100. The results show that the EAWC has been undergoing widespread and robust changes in response to global warming. The winter length in East Asia has shortened and will continue shortening owing to later onsets and earlier withdrawals, leading to a drastic contraction in length from 100 days in 1979 to 43 days (27 days) in 2100 under SSP2-4.5 (SSP5-8.5). While most regions of the East Asian continent are projected to become warmer in winter, the Japan and marginal seas of northeastern Asia will face the risks from colder winters with more frequent extreme cold events, accompanied by less precipitation. Meanwhile, the Tibetan Plateau is very likely to have colder winters in the future, though its surface snow amounts will significantly decline. Greenhouse gas (GHG) emissions are found to be responsible for the EAWC changes. GHG traps heat inside the Earth’s atmosphere and notably increases the air temperature; moreover, its force modulates large-scale atmospheric circulation, facilitating an enhanced and northward-positioned Aleutian low together with a weakened Siberian high, East Asian trough, and East Asian jet stream. These two effects work together, resulting in a contracted winter with robust and uneven regional changes in the EAWC. This finding highlights the urgency of curbing GHG emissions and improving forecasts of the EAWC, which are crucial for mitigating their major ecological and social impacts. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

The Knanaya Christians, also referred to as Thekkumbhagar or Southists, represent a distinct endogamous group within the wider community of Saint Thomas Christians of southern India. Their origins can be traced to the arrival of Jewish Christians led by Knai Thoma or Thomas of Cana, who migrated to the Malabar Coast from Persia in 345CE. Upon their arrival, they mingled with the established Christian population of the Malabar Coast, known as the Vadakkumbhagar or the Northists, whose roots extend back to the apostolic mission of Saint Thomas in the 1st century CE. However, the Knanaya Christians have successfully preserved their unique identity through the practice of endogamy, which keeps their bloodlines separate from those of the Vadakkumbhagar, while also maintaining a spiritual connection and liturgical continuity with the latter. Despite their matrimonial exclusivity, the Knanaya Christians have followed the same developmental path as the larger Thomas Christian community, sharing liturgical practices, enjoying similar privileges, facing the same challenges during the Portuguese era, experiencing divisions in the 17th century, and striving to preserve their identity. The migration of this endogamous community to other parts of the world since the mid-20th century, in similar lines with different groups of Thomas Christians, has posed challenges to their traditions and practices, especially endogamy. This paper explores how Knanaya Christians maintain and adapt their endogamous marriage traditions in transnational settings by focusing on how Knanaya religious authorities and lay members collectively negotiate these tensions—whether by reinforcing endogamy or adapting it in response to shifting realities in North American settings. Full article

Externally governed hydrogel swelling is a highly convenient yet inherently challenging process, as it requires both responsive materials and appropriately tuned external stimuli. In this work, for the first time, the influence of simultaneous action of external physical fields—ultrasound (US) and microwave heating (MW), combined with cooling—on the isothermal swelling kinetics of poly(methacrylic acid) (PMAA) hydrogel was investigated and compared with swelling under conventional thermal heating (TH) under isothermal conditions. Swelling kinetics were monitored over a temperature range of 248–318 K, under simultaneous cooling with either US, MW, or TH. The well-established Peppas model was used to determine swelling kinetics parameters, revealing a significant acceleration in the swelling process under MW (up to 48.8 times at 313 K), as well as different water penetrating mechanisms (non-Fickian diffusion) compared to TH and US (Super-case II). Additionally, it was demonstrated that the swelling conversion curves could be mathematically described using a “shrinking boundary surfaces” model. Isothermal swelling constants and the corresponding kinetic parameters (activation energy E_a and pre-exponential factor ln A) were calculated. The results confirmed that external physical fields significantly influence the thermal activation and swelling behavior of PMAA xerogels, offering insight into field-responsive transport processes in hydrogel networks. Full article

Background: Fasciola hepatica causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential roles in the parasite such as host invasion and nutrient acquisition. To characterize immune responses, we produced two recombinant F. hepatica LAPs (FhLAP1 and FhLAP2), formulated with ISCOM-matrices (IMXs) nanoparticles from Quillaja brasiliensis saponins. Methods: Forty female Corriedale sheep were assigned to four groups (n = 10): FhLAP1/IMX, FhLAP1/FhLAP2/IMX, IMX (control), and FhLAP1/Adj50 (Adjuvac 50). Animals received two subcutaneous immunizations at weeks 0 and 4 and were challenged orally with 200 metacercariae at week 6. Results: FhLAP1 and FhLAP1/FhLAP2 induced specific IgG responses, with the predominance of the IgG1 response. However, these responses were lower than those generated by FhLAP1 formulated with Adj50. A qPCR analysis revealed that FhLAP1/IMX stimulated a Th1-type response profile before the challenge, but this profile was not sustained after infection. The post-infection profile of FhLAP1/FhLAP2/IMX was more congruent with expected values despite not achieving a robust IFN-γ expression. No significant differences in the fluke burden were observed. Conclusions: Further research on the optimal antigen/adjuvant combination in ruminants is encouraged. For instance, a higher concentration of adjuvant in the formulation used in this work may enhance the strength and duration of the inflammatory response and improve protective immunity against fasciolosis. Full article

Visceral leishmaniasis is a zoonosis commonly caused in Brazil by the parasite Leishmania infantum. This protozoan parasite can infect several species of mammals, with dogs being the main reservoir in urban areas. Several methods are used to prevent the disease, including collars impregnated with 4% deltamethrin to prevent contact between the sandfly and the animal, and vaccines. Vaccines aim to stimulate an immune response that can effectively fight the parasite, with the Th1 immune response being the most desired. There are several research groups around the world dedicated to testing new immunogens against Leishmania spp. and there are currently two commercially available vaccines used to prevent the disease, Neoleish^® and Leti-Fend^®. Leish-Tec^®, a vaccine previously licensed for use in dogs in Brazil, was suspended in May 2023 due to non-compliance in some batches. This also happened with CaniLeish^®, which was discontinued by the European Commission in October 2023. These vaccines have different characteristics that influence their use as a public health measure, and therefore the objective of this review is to describe these immunogens, their characteristics, and their use as a collective prevention measure for canine visceral leishmaniasis. Full article