Search Results (493)

Lumpy skin disease virus (LSDV), a transboundary pathogen threatening cattle health in South and Southeast Asia, presents growing challenges for disease control. This study combined serological, molecular, and genomic approaches to investigate LSDV in Barura Upazila, Bangladesh. Serological screening of 424 cattle using a commercial ELISA revealed a high seroprevalence of 55.5% (95% CI: 50.7–60.3), indicating widespread exposure. Although differences were observed by age and breed, no significant associations were found with seropositivity, suggesting broad regional circulation. Real-time PCR confirmed LSDV DNA in all 20 clinically infected animals, with consistent P32 gene amplification. Two samples with low Cq values underwent whole-genome sequencing. The complete genomes of LSDV-L2/2024 and LSDV-L3/2024 showed >99.6% identity with the reference strain LSDV-29, yet carried unique genomic features, including truncated or variant ORFs and immune-related gene differences. Phylogenetic analysis of the DNA polymerase gene revealed distinct clustering: L2/2024 aligned with South Asian isolates, while L3/2024 grouped with strains from Africa, the Middle East, and Europe. These results highlight co-circulation of genetically diverse strains and possible cross-regional introductions. Overall, our findings underscore the evolutionary plasticity of LSDV and the critical need for ongoing genomic surveillance to guide targeted vaccine development and disease control strategies. Full article

Aeromonas hydrophila (A. hydrophila) is responsible for causing abdominal dropsy, swimming abnormalities, skin ulcerations, and pale gills in fish. Vaccination is an essential strategy for disease prevention in aquaculture. This study evaluated the efficacy of an oral vaccine against A. hydrophila in Ctenopharyngodon idella (C. idella). The vaccine was formulated as feed-based monovalent pellets, incorporating or spraying formalin-killed A. hydrophila on/into commercial feed with 30% crude protein. Mineral and fish oils were used as adjuvants at 10% of the feed. Prior to the trial, the experimental feed groups were subjected to quality and safety tests. Grass carp fingerlings (20 ± 5 g) were divided into seven groups (n = 20 per group): sprayed vaccinated feed with fish oil (SVFF), incorporated vaccinated feed with fish oil (IVFF), sprayed vaccinated feed with mineral oil (SVFM), incorporated vaccinated feed with mineral oil (IVFM), sprayed vaccinated feed (SVF), incorporated vaccinated feed (IVF), and a control group. Feed was provided at 3% of body weight for 60 days. Immunomodulation was investigated through lysozyme activity, antibody titers, and immunoglobulin M (IgM). The IVFF group showed significantly enhanced immunity and growth performance, with an 87% protection rate, 13% mortality, and the highest relative percentage survival (83%) following intraperitoneal A. hydrophila (6.8 × 10⁹ CFU/mL) challenge. Histological analysis indicated minimal pathological changes in the IVFF group compared to controls. Fish oil as an adjuvant enhanced immunity without adverse health effects. Overall, this study demonstrated that feed-based monovalent vaccines effectively improve immune responses and provide protection against A. hydrophila in C. idella. Full article

A 29-year-old gentleman of African descent presented to the emergency department with a three month history of a rash affecting the trunk, upper limbs, and thighs. The patient was unsure of any triggers and denied any preceding illness, new medications, illicit drug use, or recent vaccinations. On examination, there was a widespread papulosquamous eruption characterised by scaly, hyperpigmented papules and plaques involving the trunk, upper arms, and upper thighs. A definitive diagnosis was established through a diagnostic skin biopsy of a fresh lesion. Full article

SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 patients, including skin samples from 35 deceased patients who had contracted COVID-19 before the launch of the vaccine. Detection of SARS-CoV-2 in the skin was performed using transmission electron microscopy and RT-qPCR. Microscopic and molecular effects of the virus in skin were evaluated by histopathology, RT-qPCR, and immunohistochemistry (IHC). The results revealed the presence of SARS-CoV-2 and microscopic changes, including microvascular hyaline thrombi, perivascular dermatitis, and eccrine gland necrosis. There was increased transcription of TBK1 and a reduction in transcription of TNFα by RT-qPCR in the COVID-19 group. IHC revealed reduced expression of ACE2, TLR7, and IL-6, and elevated expression of IFN-β by epidermal cells. In the dermis, there was decreased expression of STING, IFN-β, and TNF-α and increased expression of IL-6 in sweat glands. Our results highlight the role of type I IFN in the skin of COVID-19 patients, which may modulate the cutaneous response to SARS-CoV-2. Full article

In fish, the innate immune system is crucial for rapid defense against pathogens. In this study, we performed transcriptome sequencing using next-generation sequencing (NGS) to identify and characterize granulocyte colony-stimulating factor (GCSF) and macrophage colony-stimulating factor (MCSF) in starry flounder (Platichthys stellatus). The GCSF gene (594 bp, 198 aa) features a conserved IL-6 domain, while the MCSF gene (621 bp, 207 aa) contains a predicted transmembrane region. Phylogenetic analysis confirmed high evolutionary conservation with other marine species. Quantitative real-time PCR revealed that GCSF is highly expressed in the skin, peripheral blood leukocytes, and muscle, with significant up-regulation in immune organs following Streptococcus parauberis infection; MCSF exhibited a similar tissue-specific expression pattern. Recombinant GCSF (rGCSF) was produced using a cell-free system and effectively enhanced leukocyte phagocytic activity at an optimal concentration of 150 μg/mL, without causing cytotoxicity in hemolytic assays. In contrast, rMCSF exhibited folding issues during purification. These findings highlight the potential of rGCSF as a molecular adjuvant to enhance immune responses in aquaculture. This study provides foundational knowledge for developing cytokine-based adjuvants, which could reduce antibiotic dependency and enhance vaccine efficacy in sustainable aquaculture systems. Full article

This article documents the first outbreak of aeromoniasis caused by Aeromonas veronii in farmed European seabass (Dicentrarchus labrax) along the Greek Ionian Sea coast. In late spring 2024, commercially sized fish exhibited anorexia, hemorrhages, and ulcers on the skin, accompanied by elevated morbidity and mortality rates. The outbreak spread rapidly across local farms in Sagiada Bay, reaching its peak in late summer, and extending into the Astakos Gulf, southern in the Ionian Sea. The postmortem examination revealed hemorrhages, organomegaly, abscess formation, and granulomatous inflammation. Aeromonas veronii was isolated from all examined individuals in nutrient media and confirmed by biochemical and molecular methods. Whole genome sequencing and phylogenetic analysis demonstrated genetic homogeneity among two strains from two different areas along the Ionian Sea and a close evolutionary relationship with other Aeromonas veronii strains from the Aegean Sea. Although genetically similar, the isolates exhibited differences in phenotypic and biochemical characteristics, indicating regional variability. The present study provides an overview of the pathology, clinical characteristics and progression of aeromoniasis in Ionian Sea aquaculture, highlighting the need for continued monitoring, in-depth genomic and phenotypic assessment, and the design of region-specific preventive strategies, including autogenous vaccines, for effective disease management. Full article

Background: Lumpy skin disease (LSD) is major transboundary disease affecting cattle and water buffaloes, indirectly causing huge socio-economic losses. Following its first outbreak in India in 2019, the heterologous Goatpox (Uttarkashi strain) vaccine mitigated LSD. Objective: Due to limited data on the spatiotemporal distribution of the disease, this study investigates its dynamics and presents findings from a field study conducted in Maharashtra, India. This study evaluates the safety, immunogenicity, and duration of immunity provided by a heterologous vaccine. Additionally, it examines post-vaccination responses in relation to factors such as age, gender, and breed. Methods: This study employed spatiotemporal analysis of lumpy skin disease (LSD) outbreaks from 2020 to 2024 using GeoDa (v1.22), incorporating Moran’s I and Getis-Ord Gi* statistics to identify spatial clustering patterns. A randomized field trial was conducted to evaluate vaccine safety and immunogenicity in 657 cattle across seven districts. Humoral immune responses were assessed using the serum neutralization test (SNT) and indirect enzyme-linked immunosorbent assay (ELISA), while cell-mediated immunity was evaluated via Interferon-gamma (IFN-γ) ELISA. For sero-monitoring, a total of 1925 serum samples from 22 districts were analyzed. Additionally, statistical analyses (n = 1925), including the Kappa Index, ANOVA, and logistic regression, were performed using SPSS v27 to investigate the influence of factors such as age, sex, and breed (significance level: p < 0.05). Results: LSD exhibited significant spatial clustering across Maharashtra. The Goatpox vaccine was 100% safe, with no adverse reactions. Protective antibody titers (≥1:8) were observed in 96.9% of vaccinated cattle by 14–21 days post-vaccination (dpv), peaking at 60 dpv before declining at 150 dpv. The cell-mediated immune response peaked at 28 dpv. Clinical monitoring for one year showed that only 2% of vaccinated cattle developed mild LSD symptoms after nine months, with no mortality. At six months post-vaccination, seroconversion was 69.7%, with breed significantly influencing seropositivity. Conclusions: This study confirms the Goatpox vaccine’s safety and strong immunogenicity in cattle, marking its first large-scale evaluation in the Indian subcontinent. Further research is needed to assess long-term immunity and protection against virulent LSD strains. Full article

Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity. Methods: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine cell line. Results: Vaccination with citENO1, but not unmodified ENO1 (umENO1), induced a greater percentage of activated CD8+ PD-1+ T cells and effector memory T cells in skin-draining lymph nodes (SDLNs). Remarkably, the citENO1 vaccine delayed tumor growth and prolonged overall survival, which was further enhanced by PD-1 blockade. Conclusions: Our data suggest that cancer-restricted post-translational modifications provide a source of vaccines that induce an anti-cancer immune response. Full article

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation, impaired epidermal barrier function, and immune dysregulation. The Th17/IL-23 axis plays a central role in its pathogenesis, promoting the production of key pro-inflammatory cytokines such as IL-17, IL-23, and TNF-α, which sustain chronic inflammation and epidermal remodeling. Emerging evidence suggests that SARS-CoV-2 may trigger new-onset or exacerbate existing psoriasis, likely through viral protein-induced activation of toll-like receptors (TLR2 and TLR4). This leads to NF-κB activation, cytokine release, and enhanced Th17 responses, disrupting immune homeostasis. Erythrodermic psoriasis (EP), a rare and severe variant, presents with generalized erythema and desquamation, often accompanied by systemic complications, including infection, electrolyte imbalance, and hemodynamic instability. In a murine model of SARS-CoV-2 infection, we found notable cutaneous changes: dermal collagen deposition, hair follicle destruction, and subcutaneous adipose loss. Parallel findings were seen in a rare clinical case (only the third reported case) of EP in a patient with refractory psoriasis, who developed erythroderma after off-label initiation of dupilumab therapy. The patient’s histopathology closely mirrored the changes seen in the SARS-CoV-2 model. Histological evaluations also reveal similarities between psoriasis flare-ups following dupilumab treatment and cutaneous manifestations of COVID-19, suggesting a shared inflammatory pathway, potentially mediated by heightened type 1 and type 17 responses. This overlap raises the possibility of a latent connection between SARS-CoV-2 infection and increased psoriasis severity. Since the introduction of COVID-19 vaccines, sporadic cases of EP have been reported post-vaccination. Although rare, these events imply that vaccine-induced immune modulation may influence psoriasis activity. Our findings highlight a convergence of inflammatory mediators—including IL-1, IL-6, IL-17, TNF-α, TLRs, and NF-κB—across three triggers: SARS-CoV-2, vaccination, and dupilumab. Further mechanistic studies are essential to clarify these relationships and guide management in complex psoriasis cases. Full article

Background/Objectives: Q-VAX vaccine, approved in Australia, prevents Q fever. However, individuals with prior Coxiella burnetii (Cb) infection have an increased risk of adverse reactions, requiring pre-vaccination screening by an intradermal hypersensitivity skin test for cell-mediated immune memory and a serological assay for anti-Cb antibodies. The week-long interval for skin test assessment limits efficient vaccination. This study evaluated a standardized interferon-γ release assay (IGRA) as a potential skin test alternative. Methods: Immune assays were compared in Australian populations with different incidences of prior Cb exposure. Cell-mediated immunity was assessed by the Q-VAX skin test and IGRA. Serological status was evaluated with established diagnostic assays. Hypothetical vaccine eligibility decisions using combined IGRA and serology results were compared with actual clinical decisions made using current guidelines. Results: All tests performed better in detecting prior infection than in detecting prior vaccination. Only the IGRA identified all individuals with a known history of Q fever. Agreement between the skin test and IGRA was limited. Moderate agreement was observed between hypothetical vaccine eligibility determinations based on IGRA plus serology results and actual clinical decisions. IGRA-positive but serology- and skin test-negative individuals received Q-VAX without clinically significant side effects, suggesting that elevated IGRA responses alone are not predictive of susceptibility to vaccine reactogenicity. Conclusions: The IGRA is not yet a suitable skin test replacement when assessing eligibility for Q fever vaccination, despite the significant limitations of the latter. We offer recommendations for designing future studies that might allow the development of appropriate guidelines for IGRA use in vaccine eligibility screening. Full article

The incidence of melanoma is increasing globally, even in the wake of increased risk factor awareness and a growing body of advanced therapeutic options. It is apparent that the treatment of melanoma will remain a topic of worry in areas of the world under high ultraviolet exposure and areas that harbor individuals with fair skin phenotypes. In the wake of such concern, the potential of immunotherapy and various targeted therapeutics to treat late-stage melanoma is increasing. In addition to the growing arsenal of PD-1 and PD-L1 immune checkpoint inhibitors, other targeted therapies are being developed and tested to treat melanoma. BRAF/MEK inhibitors target a key proliferative pathway in melanoma, offering clinical benefit but limited durability. Next-generation agents and triplet therapy with immunotherapy aim to improve outcomes. Androgen receptor signaling may also modulate responses to both targeted and immune-based treatments. Bispecific T cell engagers assist with guiding the body’s own T cells to tumors where they release toxins that kill the tumor cell. Personalized neoantigen vaccines target tumor-specific antigens by sequencing a patient’s cancerous cells to create tailored vaccines that elicit a strong and specific immune response. Tumor-infiltrating lymphocytes are autologous lymphocytes reinfused back into the host that are showing efficacy in the treatment of advanced melanoma. Together, these therapies are advancing the arsenal of chemotherapeutic options that can be used to inhibit the progression of melanoma. Full article

Objectives: This study aims to assess the adjuvant effects of lentinan and its combination with Mn(J), a manganese-based colloidal adjuvant, on the BG (fusion protein BfrB-GrpE of Mycobacterium tuberculosis) subunit vaccine. Methods: A rabbit skin infection model was established to evaluate the immune protection conferred by the BG–lentinan vaccine, the BG–lentinan/Mn(J) vaccine, and the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis. Rabbits were vaccinated at weeks 0, 2, and 4. Six weeks post-vaccination, antigen-specific IgG levels were measured, followed by a BCG skin challenge. Results: Both the BG–lentinan and BG–lentinan/Mn(J) vaccines significantly increased antigen-specific IgG levels against BfrB and GrpE in rabbits (p < 0.05). Furthermore, these vaccines accelerated the pathological process following BCG infection. The bacterial load in nodules was notably reduced, with the BG–lentinan vaccine group exhibiting the lowest levels (p < 0.01). Conclusions: Lentinan and its combined adjuvant, lentinan/Mn(J), significantly enhance the immune response elicited by the BG tuberculosis subunit vaccine, providing effective protection. Full article

Background: The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though no randomized trials have yet confirmed its effectiveness. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between 1 September 2022 and 15 June 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until 31 March 2024. The primary endpoint was symptomatic mpox occurrence ≥14 days post-vaccination. Results: The primary analysis included 1028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7–13.7). Mpox occurred in eight participants (0.8%): three vaccinated and five unvaccinated (HR 0.6; 95% CI 0.21–1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 450/1058 (42.5%) participants, persisting >6 months in 107 of them (23.8%). Conclusions: The low incidence of mpox during the study period resulted in a limited number of endpoint events, precluding robust conclusions on the efficacy of the MVA-BN vaccine as pre-exposure prevention for mpox. However, our analysis, which accounted for key confounders such as exposure behaviors, yielded results consistent with previous studies suggesting the effectiveness of the vaccine in the mpox setting. Full article

Background: Bovine tuberculosis (bTB) is an infectious disease which causes significant damage to the farming industry and remains a disease of global significance. Although control strategies have focused on a test and cull approach primarily based around specific cell-mediated immune responses, serological assays are increasingly being used as a supplementary test alongside skin testing and interferon-gamma release (IGRA) assays. The UK is moving towards the use of the Bacillus Calmette–Guérin (BCG) vaccination of cattle as an additional targeted control tool against bTB. However, there are concerns over its potential impact on the outcomes of bTB diagnostic tests and other non-TB assays, such as serological tests for Mycobacterium avium subsp. paratuberculosis (MAP). Methods: We investigated the performance of commercially available serology tests designed to detect bTB and MAP using serum samples from BCG-vaccinated animals which were subsequently infected with Mycobacterium bovis (M. bovis). Results: BCG vaccination per se did not significantly impact the specificity of serological diagnostic tests for bTB or Johne’s disease. However, increased numbers of false-positive responses in bTB serology tests were seen in BCG-vaccinated animals 3 weeks following a tuberculin skin test, where up to 23% and 54% of animals gave a positive result in IDEXX and Enferplex tests, respectively. Furthermore, M. bovis infection gave rise to false-positive test results for Johne’s disease, irrespective of the animals’ prior BCG vaccination status. Conclusions: Caution should be taken when assessing results from serology tests for bTB if tuberculin skin testing has occurred shortly before collection of blood from BCG-vaccinated cattle. Furthermore, these results highlight the potential for misdiagnosis of MAP infection when using serology tests in bTB-infected cattle. Full article

(1) Background: Contagious ecthyma, also known as orf, is an epitheliotropic zoonotic disease caused by the orf virus (ORFV), primarily affecting the skin and mucous membranes of ruminants such as goats and sheep, leading to the formation of papules and pustules. Vaccination is the most effective way to prevent this disease in susceptible animals; however, traditional attenuated vaccines carry the potential risk of reversion to virulence. Therefore, there is an urgent need to develop safe and effective vaccines for the prevention and control of orf. (2) Methods: In this study, building upon the previously constructed ORFV three-gene deletion strain rGS14-TrypMut, we employed homologous recombination to knock out the VIL-10 gene and successfully constructed a four-gene deletion strain, rGS14-QuadMut. We evaluated its in vitro growth characteristics, safety, and protective efficacy in a challenge model. (3) Results: The in vitro results show that rGS14-QuadMut had a replication ability similar to that of other two-gene deletion strains, with good genetic stability. In in vivo experiments, compared to rGS14-TrypMut, rGS14-QuadMut caused only mild redness and swelling at the inoculation site, with a faster healing rate, indicating better safety. Additionally, rGS14-QuadMut induced strong differentiation of CD4⁺ and CD8⁺ T cells, increased the CD4⁺/CD8⁺ ratio, and primarily stimulated a Th1-type immune response, with significant changes in cytokine levels, including IL-8, IFN-γ, and IL-2. In the challenge protection experiment, both rGS14-QuadMut and rGS14-TrypMut provided 100% protective efficacy. In conclusion, rGS14-QuadMut demonstrated enhanced safety without compromising immune protection efficacy and is a promising candidate for an orf live vaccine strain. Full article