Search Results (221)

Background: Since the introduction of Pasteur’s rabies vaccine in 1885, rabies prophylaxis and post-exposure prophylaxis (PEP) have been widely administered globally under the recommendation of the World Health Organization (WHO). However, 124 documented cases of PEP failure had been reported worldwide between 1980 and 2023. Additionally, sporadic media reports from China showed occasional PEP failures between 2017 and 2024. Rabies remains a serious public health problem in over 150 countries and regions. Methods: In this review, we summarize PEP procedures recommended by the Advisory Committee on Immunization Practices (ACIP) and the WHO. We also analyze potential contributing factors to PEP failure, propose a concept of circulating antibodies, and discuss their roles in PEP. Furthermore, we summarize key guidelines for clinical trial design from the U.S. Food and Drug Administration (FDA) and China’s Center for Drug Evaluation (CDE), as well as the latest developments in monoclonal antibody (cocktail) therapies. Results: Adherence to core PEP practices, such as wound cleansing, infiltration of wounds with immunoglobulin (mAbs), and administration of vaccines, and broader societal involvement are crucial for preventing rabies infection in most cases. For high-risk exposures or immunocompromised individuals, the provision of circulating antibodies through high-dose human rabies immune globulin (HRIG) or mAbs is of utmost importance for preventing PEP failure. Conclusions: Early, high-concentration circulating antibodies are important for preventing PEP failure. Addressing the global issue of rabies requires involvement of the entire society. Only through collective efforts can we tackle this neglected disease and achieve WHO’s goal of “zero by 30”. Full article

Immunosuppression dramatically increases tissue and organ susceptibility to infection, injury, and even cancer. This poses a serious threat to human and animal health. In a previous study, we established a platform for high-throughput design and screening of multifunctional peptides. Using this platform, we successfully identified a novel hybrid peptide, VLP-Aβ (VA), which exhibits both immunomodulatory and antioxidant properties. This study aimed to evaluate the immunomodulatory activity of VA and investigate the underlying molecular mechanisms. In the cyclophosphamide (CTX)-induced immunodeficient mouse model, VA significantly alleviated CTX-induced weight loss. It also restored thymus and spleen indices, and increased serum immunoglobulins (IgA, IgM, IgG) and cytokines (TNF-α, IL-6, IL-1β) levels. VA also improved splenic lymphocyte proliferation, CD4⁺/CD8⁺ T cell ratios, and NK cell cytotoxicity. At the cellular level, western blot analysis showed that VA activated the TLR4-NF-κB pathway in RAW264.7 macrophages. Mechanistically, inhibition of the MD2 protein by L6H21 abolished VA’s immunomodulatory effects. This confirms MD2 as a critical mediator. Molecular docking and dynamics simulations revealed that VA binds stably to the hydrophobic pocket of MD2. These findings suggest that VA exerts immunomodulatory effects by stimulating MD2 and activating the TLR4-NF-κB pathway, which provides new ideas, techniques, and approaches for the development of novel peptide immunomodulators. Full article

The aim of this systematic review was to evaluate the current evidence for the involvement of epithelial-derived extracellular vesicles (EVs) in Immunoglobulin E (IgE)-mediated allergic sensitisation. Original clinical and research studies specifically examining the effect of epithelial-derived EVs in IgE-mediated allergic sensitisation were included. Non-IgE mediated allergies, abstracts and review articles were excluded. A total of 18 publications were identified from three databases (EMBASE, Web of Science and PubMed) that indicate epithelial-derived EVs have the potential to promote tolerance or allergic sensitisation. For example, epithelial-derived EVs have the potential to promote IgE-mediated allergic sensitisation by delivering mRNAs that promote T helper 2 (Th2) polarisation and cytokine secretion, or promote tolerance through the induction of T regulatory (Treg) cells. The results also indicate that the potential role of epithelial-derived EVs in IgE-mediated allergic sensitisation may be dependent on the barrier, with all publications related to intestinal epithelium driving tolerance, but publications on nasal and bronchial/alveolar epithelia gaving mixed effects. No publications were found on cutaneous epithelia. Taken together, the literature suggests that epithelial-derived EVs play a key role in influencing IgE-mediated allergic sensitisation. Further research examining all epithelial barriers, using both robust human in vitro models that give more biologically relevant information, as well as clinical studies, are required to further characterise the role of epithelial-derived EVs in IgE-mediated allergic sensitisation. Full article

Respiratory viruses continue to present serious health challenges to human wellness. Growing evidence suggests that the more severe and damaging effects and symptoms of influenza, rhinovirus (RV), respiratory syncytial virus (RSV), and COVID-19 may primarily result from their common ability to disorganize the body’s healthy immune response. The simultaneous over-stimulation of several reactive oxygen species (ROS) pathways and concurrent suppression of bioavailable Nitic Oxide (NO) contribute to an immune disbalance that can lead to cellular oxidative distress and an excessive inflammatory response. This study evaluated the real-time, acute ability of a single, orally administered 50 mg encapsulated dose of a plant-based dietary supplement (“PB-Blend”), compared to 1000 mg of Vitamin C as a positive control, to modulate multiple ROS associated with a dampened immune response, as well as NO and other markers of inflammation, in a cohort recovering from a moderate course of COVID-19. This randomized, double-blind study was performed on 28 individuals 18–24 days after a moderate COVID-19 infection. Participants were orally supplemented with a single encapsulated dose of either 50 mg of PB-Blend or 1000 mg Vitamin C as a positive control. Changes in the levels of bioavailable NO (measured as circulating NOHb) were assessed, as well as the ex vivo cellular formation of mitochondrial, NOX2-, iNOS-, and TNFα-dependent ROS. All parameters were measured in real time before ingestion (baseline), and then at 30, 60, 120, and 180 min after administration. ROS were measured using a portable electron paramagnetic resonance (EPR) spectrometer. Inflammatory, immunity (hsCRP and TNFα plasma levels), interleukin (IL1, IL6, IL8, and IL10), cytokine (IFNγ, TNFα, and NF-κB), and immunoglobulin (IgA, IgM, IgG, and IgE) profiles were also followed. In addition to laboratory and cell function investigations, we performed clinical cardio ergometry, blood O₂ saturation, and respirometry examinations. As hypothesized, the collected baseline data from this study group confirmed that mitochondrial, NOX2, and iNOS enzymatic systems were strongly involved in the generation of ROS at 18–24 days following a positive COVID-19 PCR test. Acute single-dose supplementation of 50 mg PB-Blend had a multifunctional impact on ROS and significantly inhibited the following: (a.) mitochondrial ROS levels by up to 56%; (b.) iNOS by up to 60%; and (c.) NOX2-dependent ROS generation by up to 49%. Moreover, 1000 mg Vitamin C supplementation exhibited narrower ROS-mitigating activity by solely inhibiting NOX2-dependent ROS generation by 45%. Circulating NOHb levels were significantly increased after PB-Blend administration (33%), but not after Vitamin C administration. PB-Blend and Vitamin C exhibited similar potential to reduce ex vivo high dose TNFα (200 ng/mL)-induced H₂O₂ formation. These results suggest that 50 mg of PB-Blend has the potential to modulate disbalanced mitochondria, iNOS, and NOX2 enzymatic systems that can be engendered during respiratory viral infection and subsequent recovery. Moreover, PB-Blend, but not Vitamin C, showed potential to upregulate bioavailable NO, which is known to decline under these conditions. Based upon these observations, PB-Blend could be considered an alternative to, or to be used in tandem with Vitamin C in applications that promote immune support and recovery during seasons of heightened respiratory viral risk (e.g., “flu season”). Full article

Background: Human milk (HM) provides critical immunological support to neonates, serving as a key component of passive immunity during early life. Objectives: The main aim of this cohort study was to compare the concentrations of lactoferrin (Lf), secretory immunoglobulin A (SIgA), C-reactive protein (CRP), and their ratios to total protein levels in the colostrum of postpartum women infected with SARS-CoV-2 and healthy controls. Methods: Colostrum samples (3–5 mL) were collected from 40 mothers (20 infected, 20 healthy) during the first wave of the COVID-19 pandemic in Poland. Concentrations of Lf, SIgA, and CRP were analyzed using ELISA, and total protein content was measured using the bicinchoninic acid assay (BCA). Results: The presence of specific anti-SARS-CoV-2 SIgA antibodies was assessed via cassette serological lateral flow detection tests. Significant differences were observed in Lf (p = 0.04) and SIgA (p = 0.03) concentrations, both lower in the COVID-19 group. Lactoferrin medians were 12.30 g/L (infected) and 14.95 g/L (healthy), and for SIgA: 9.15 g/L vs. 15.01 g/L, respectively. No significant difference was found in CRP levels. Interestingly, the Lf/Protein ratio was significantly higher in the infected group (p = 0.03), whereas the SIgA/Protein ratio did not differ. Furthermore, 75% of infected mothers had positive anti-SARS-CoV-2 SIgA results. These mothers also showed a higher Lf/Protein ratio. Among healthy controls, 90% had negative test results. Conclusions: These findings suggest a potential compensatory role of lactoferrin in the nonspecific immune response to SARS-CoV-2, though stress-related reductions in SIgA levels cannot be excluded. Full article

Various inhibitors targeting T-cell immunoglobulin and mucin-containing molecule 3 (TIM3) aimed at reversing T-cell exhaustion for better immunotherapy outcomes have demonstrated limited clinical efficacy as monotherapy, with the underlying mechanisms remaining ambiguous. TIM3 is markedly expressed in dendritic cells (DCs), and the inconsistent research findings on its role in myeloid cells underscore its vital function within DCs. Through the establishment of an in vitro differentiation model generating mature dendritic cells (mDCs) under TIM3-targeted interventions, combined with an RNA sequencing analysis, this investigation systematically examined TIM3-mediated regulation and ligand interactions in human primary DCs. The findings indicate that TIM3 inhibition hinders DC maturation, which subsequently diminishes the antigen-presenting capacity of DCs, ultimately leading to immune suppression in T cells. These findings collectively establish TIM3 as a regulator of DC differentiation that promotes DC maturation while optimizing the antigen-processing and presentation capacity. This study elucidates the rationale behind the suboptimal efficacy of TIM3 inhibitors and advocates for retaining TIM3 signaling pathways in DCs. Full article

Most donor human milk (HM) banks use Holder pasteurization (HoP) to ensure microbiological safety, although it can degrade essential bioactive factors for newborns. This study evaluates the innovative ultra-high-pressure homogenization (UHPH) technology as a potential alternative. Listeria innocua, Staphylococcus carnosus, Franconibacter helveticus (formerly named Cronobacter helveticus) and Escherichia coli strains were used as surrogates for common HM pathogens according to European Milk Bank Association (EMBA) guidelines, to evaluate the efficacy of new technologies. A reconstituted powder milk formula inoculated with these strains was used to determine the most efficient conditions (those to achieve a lethality of ≥5 Log), applying treatments from 150 to 300 MPa. These treatments were later validated using inoculated HM with the same strains. Immunoglobulin (sIgA, IgG, IgM) retention was also evaluated and compared with HoP. Results showed that UHPH treatments at 200 MPa achieved a lethality > 5 Log for all strains, except for St. carnosus, which required 250 MPa for complete inactivation in HM. Unlike HoP, UHPH at 200 and 250 MPa did not significantly reduce the basal concentration of sIgA, IgG, or IgM compared with raw HM. These findings suggest UHPH as a promising alternative to HoP, maintaining both microbiological safety and immunological quality. Full article

Dengue is a neglected disease mainly affecting tropical and subtropical countries. The diagnosis of dengue fever is still a problem since most of it is made from whole or recombinant DENV proteins, which present cross-reactions with other members of the Flavivirus family. Therefore, there is still a huge demand for new diagnostic methods that provide rapid, low-cost, easy-to-use confirmation. Thus, in this study, we developed an affordable electrochemical biosensor for rapidly detecting immunoglobulin G (IgG) serological antibodies in the sera of DENV-infected patients. An identified linear B-cell epitope (DENV/18) specific for DENV 1–4 serotypes recognized by IgG in patient sera was selected as a target molecule after a microarray of peptides using the SPOT-synthesis methodology. After chemical synthesis, the DENV/18-peptide was immobilized on the surface of the working electrode of a commercially available screen-printed gold electrode (SPGE). The capture of DENV-specific IgG allowed for the formation of an immunocomplex that was measured by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using a potassium ferrocyanide/ferricyanide ([Fe(CN)₆]^3−/4−) electrochemical probe. An evaluation of the biosensor’s performance showed a detection limit of 100 µg mL⁻¹ for the synthetic peptides (DENV/18) and 1.21 ng mL⁻¹ in CV and 0.43 ng mL⁻¹ in DPV for human serum, with a sensitivity of 7.21 µA in CV and 8.79 µA in DPV. The differentiation of infected and uninfected individuals was possible even at a high dilution factor that reduced the required sample volumes to a few microliters. The final device proved suitable for diagnosing DENV by analyzing real serum samples, and the results showed good agreement with molecular biology diagnostics. The flexibility to conjugate other antigenic peptides to SPEs suggests that this technology could be rapidly adapted to diagnose other pathogens. Full article

The overuse of antibiotics in animal husbandry has driven the search for alternative strategies to combat zoonotic pathogens. Foodborne zoonotic diseases caused by pathogenic bacteria pose a significant threat to human health, and therefore food safety should be a priority. This study investigates the in vitro inhibitory effects of chicken egg yolk immunoglobulin Y (IgY) on the growth and viability of three major foodborne pathogens: Campylobacter jejuni, Salmonella spp., and Escherichia coli. IgY was isolated from immunized hen egg yolks using a modified water dilution method, and its antigen-specificity confirmed through agglutination assays. Growth inhibition was evaluated across multiple doses and time points, revealing a dose-dependent bacteriostatic effect against all tested pathogens. A single dose of IgY (0.5 mg/mL) significantly reduced C. jejuni counts by up to 7 log, while repeated doses were required for Salmonella spp. and E. coli. These findings highlight egg yolk immunoglobulin’s potential as a source of sustainable, effective, ethical, readily available, and inexpensive antibiotic substitutes in livestock management. Future research will focus on validating these results in vivo and exploring large-scale production of IgY for practical application in animal healthcare. Full article

There is a global and increasing demand for natural ingredients that support the human immune response. In this study, the immunomodulatory effect and mechanism of action of rice bran extract fermented by Lentinus edodes was investigated. The potential immunomodulatory effect of fermented rice bran (FRB) and processed rice bran (RB) was evaluated using male BALB/c mice whose immunity was lowered by Cyclophosphamide (CY). The changes in the weight of the thymus and the spleen, immunoglobulins, and cytokine expressions were measured as biomarkers of immunomodulating potential after 14 days of oral administration of FRB and RB (0.5 g/kg-body weight (b.w.), respectively). The FRB and RB groups treated with CY resulted in increased weight of the thymus (1.73 ± 0.40 and 1.45 ± 0.43 mg/g-b.w., respectively) compared to the CY-treated control group (1.05 ± 0.36 mg/g-b.w.). The levels of the immunoglobulin (Ig) G in the group treated with FRB (21.98 ± 2.17, p < 0.01) were significantly increased when compared to the RB group (18.48 ± 1.52 μg/mL, p < 0.01). The expression of serum cytokines, including IL-1α (p < 0.05), IL-2 (p < 0.05), IL-6 (p < 0.001), IL-12 p70 (p < 0.01), IFN-γ (p < 0.01), and TNF-α (p < 0.01) were also significantly increased by the administration of FRB (0.5 g/kg-b.w.). Similarly, the expression of spleen cytokines, including IL-1α (p < 0.05), IL-2 (p < 0.05), IFN-γ (p < 0.01), and TNF-α (p < 0.05), was also significantly increased in the group receiving the FRB (0.5 g/kg-b.w.). The natural killer cell (NK) cell activities at a 1:25 ratio of YAC-1 cells to splenocytes were significantly increased in positive control red ginseng extract 0.5 g/kg (38.64 ± 2.13%, p < 0.05), FRB (34.85 ± 3.45%, p < 0.05), and RB (25.00 ± 4.18%), compared to that of negative control CY group (12.67 ± 3.23%). These results suggest that FRB administration could stimulate the innate immune system by increasing the expression of cytokines in splenocytes and serum, especially IFN-γ, IL-2, and IL-12 (p70), which are associated with TNF-α and NK cell activities. The above results could provide the biochemical rationale to further evaluate the use of FRB for immunomodulatory applications. Full article

The erythrocyte sedimentation rate (ESR) measures the rate at which erythrocytes aggregate and sediment in a fixed time in an anticoagulated blood tube and is expressed as a speed (mm/h). The ESR is still widely used in human medicine mainly as a modified or alternate method to the original Westergren. In veterinary medicine, it was employed in the 1940s–1960s after which it was gradually abandoned or rarely employed. More papers using the Westergren method have been published in dogs rather than in cats. In recent years, the test has regained importance. This narrative review describes the principle of ESR, which is related to the increase in a few acute response proteins such as fibrinogen, immunoglobulin M, and α2-macroglobulin which act to aggregate RBCs. Reference intervals were established for dogs and cats for the original and modified Westergren method. The ESR is mainly used to detect inflammatory conditions derived from infection, urinary or orthopedic disorders, and also miscellaneous diseases. The application of the modified ESR is supported by appropriate reference intervals; however, further studies are needed to assess the influence of age, sex, and breed both for dogs and cats. Full article

Background: Argonautes (AGOs) are a type of protein that degrade specific messenger RNAs, consequently reducing the expression of a specific gene. These proteins consist of small, single-stranded RNA or DNA and may provide a route for detecting and silencing complementary mobile genetic elements. In this research, we investigated which AGO(s) were involved in Kawasaki disease (KD). Methods and Materials: We obtained mRNA-level gene expression profiles from leukocyte samples that had previously been gathered in another study and uploaded to the NCBI GEO database. The Human Transcriptome Array (HTA 2.0) analysis included 50 children with KD prior to IVIG (KD1), 18 children with KD three weeks post-IVIG (KD3), 18 non-febrile controls (HC), and 18 febrile controls (FC), which were arranged in the quoted publications for all materials and methods in order to collect data. We used the default value of the commercialized microarray tool Partek to perform an analysis of variance and determine any significant fold changes (KD1, KD3, HC, and FC individually). Results: The data revealed that the AGO2 and AGO4 genes displayed significant within-group differences with p = 0.034 and 0.007, respectively. In AGO2, significant differences were observed between KD1 vs. HC + FC with p = 0.034. KD1 appears higher than the other specimens in AGO4, with significant differences between KD1 and HC (p = 0.033), KD1 and FC (p = 0.033), KD1 and KD3 (p = 0.013), and KD1 and HC + FC (p = 0.007). We observed no substantial differences in AGO1 or AGO3 (p > 0.05). There were no significant differences between AGO(s) and coronary artery lesions or intravenous immunoglobulin resistance. (p > 0.05) Conclusion: Endothelial cell inflammation and injury, two basic pathological mechanisms, are thought to be involved in coronary endothelial dysfunction in KD. AGO2 and AGO4 are likely to participate in the endothelial dysfunction of children with KD, with AGO4 potentially playing a key role, while AGO1 and AGO3 appear not to participate. Full article

Background. Naturally occurring human antibodies against glycans recognize and quickly eliminate infectious bacteria, viruses and aberrantly glycosylated neoplastic malignant cells, and they often initiate processes that involve the complement system. Methods. Using a printed glycan array (PGA) containing 605 glycoligands (oligo- and polysaccharides, glycopeptides), we examined which of the glycan-binding antibodies are able to activate the complement system. Using this PGA, the specificities of antibodies of the IgM and IgG classes were determined in the blood serum of healthy donors (suggested as mostly natural), and, then, using the same array, it was determined which types of the bound immunoglobulins were also showing C3 deposition. Results. It was found that about 30% of anti-glycan antibodies in human serum detected by the PGA did not activate the complement. They were mostly IgGs and directed to bacterial O-antigens; no apparent common structural motif within their target polysaccharides was found. Antibodies to blood group systems ABO and Forssman, xeno-antigens, a number of polysaccharides from various strains of S. enterica, E. coli and P. alcalifaciens, as well as small fragments of bacterial polysaccharides were recognized by complement-activating antibodies as expected. A complement-activating antibody was affinity-isolated on glycan-Sepharose from human serum, and, in the presence of the complement, it lysed red blood cells coated with the same glycan (kodecytes, where glycans expressed on biological membranes), while an isolated complement non-activating antibody did not, which confirms the validity of the solid-phase PGA results. Conclusions. Thus, ~30% of human anti-glycan antibodies lack the ability to activate the complement system. The function of the widely represented immunoglobulins that do not cause C3 deposition remains unclear. Full article

Benzo[a]pyrene (B[a]P) is a hazardous polycyclic aromatic hydrocarbon that accumulates in several environmental matrices as a result of incomplete combustion. Its presence, carcinogenic properties, and tendency for bioaccumulation provide significant risks to human health and the environment. The objective of this study is to create an immunoassay for the detection of benzo[a]pyrene utilizing immunoglobulin Y antibodies. An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was utilized to develop a speedy, straightforward, sensitive, and economical approach for detecting B[a]P residues. Following the immunization of hens with the hapten pyrenebutyric acid-bovine serum albumin (PyBA-BSA), the IgY antibody extracted from egg yolk was utilized to identify B[a]P residues. To evaluate antibody specificity, six PAH derivatives—PyBA, B[a]P, Chrysene, Benzo[b]fluoranthene, Benzo[a]anthracene, and Benzo[k]fluoranthene—were examined in the experiment to compete for binding with PyBA. The findings indicate that the antibody had considerable affinity for Chrysene (1.15%), Benzo[b]fluoranthene (311.32%), Benzo[k]fluoranthene (10.62%), Benzo[a]anthracene (22.82%), and PyBA (9.55%). Nonetheless, its affinity for B[a]P remained at 100%. The recovery range for grilled pork samples spiked with B[a]P doses of 10.00–0.1 μg/mL was 74.99% to 143.11%. This study utilized a polyclonal antibody, employing the IgY antibody for the inaugural development of an immunoassay to detect benzo[a]pyrene. The ELISA had a higher IC₅₀ value compared to the other immunoassays; however, it yielded good results. This immunoassay signifies a substantial progression in environmental analytical chemistry, offering a cost-effective and accessible technique for the detection of B[a]P to protect human health and the environment. Full article

Background: Severe clinical manifestations of multisystem inflammatory syndrome in children (MIS-C) are associated with the dysregulation of immune response following SARS-CoV-2 infection. Therefore, we analyzed the levels of 10 selected cytokines at admission to estimate disease severity and to predict the length of hospitalization. In remission samples, these mediators were followed after intravenous immunoglobulin (IVIG) treatment before discharge. Methods: Thirty-five MIS-C patients at the age of 8.4 ± 4.1 years and 11 clinical controls were included. Acute MIS-C patients were divided into two severity subgroups based on their clinical score determined by the WHO criteria. Serum concentrations of IFN-γ, IL-1α, IL-1RA, IL-8, IL-10, IL-17A, IL-18, IP-10, MCP-1, and TNF-α were measured by MILLIPLEX^® Human Cytokine/Chemokine panel, while ACE2 activity was determined by a fluorescent kinetic assay. These results were correlated with routinely determined laboratory parameters and clinical characteristics. Results: MIS-C patients demonstrated significantly elevated baseline levels of most of these cytokines compared to controls. Even higher concentrations of IL-18, TNF-α and ferritin with reduced lymphocyte count were found in severe subjects with elevated clinical scores of 4–5 compared to moderate cases with a clinical score of 1–3. Furthermore, the development of cardiovascular dysfunction and prolonged hospitalization (≥8 days) were related to augmented ACE2 and IL-6 levels. IL-18, IL-1RA, IL-10 and TNF-α were diminished in response to IVIG treatment in remission samples. Finally, pre-treatment IL-18 (≥516.8 pg/mL) and TNF-α (≥74.2 pg/mL) effectively differentiated disease severity in MIS-C with AUC values of 0.770 and 0.750, respectively. Conclusions: IL-18 and TNF-α have a prognostic value in disease severity at admission and are capable of monitoring the efficacy of IVIG treatment in MIS-C. Full article