Search Results (20,356)

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle. This spreads through direct contact and insect vectors, significantly affecting global cattle farming. Despite the availability of vaccines, their efficacy is limited by poor prophylaxis and adverse effects. Our study aimed to identify the potential inhibitors targeting the LSDV-encoded DNA polymerase protein (gene LSDV039) for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as being potent binders among 380 phytocompounds, with respective affinities of −8.97 and −7.20 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (−9.86 and −8.86 kcal/mol) among 718 FDA-approved antiviral drugs. Simulating the molecular dynamics of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin’s superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF, but fluctuated in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. This study highlights the promising potential of using repurposed drugs and phytocompounds as potential LSD therapeutics. However, extensive validation through in vitro and in vivo testing and clinical trials is crucial for their practical application. Full article

Proteins present in blood samples from Atlantic salmon (Salmo salar) infected with salmon lice (Lepeophtheirus salmonis) were analyzed using liquid chromatography–high-resolution mass spectrometry. Bioinformatic analyses revealed 1820 proteins, of which 58 were assigned to lice. Among these, peroxiredoxin-2, an antioxidant protein, was found relevant with respect to blood feeding of the parasite. The three-dimensional structure analysis of the protein revealed a surface amino acid sequence of interest. A 13-amino-acid peptide was selected as a potential antigen due to its predicted solubility, antigenicity, probable non-allergenic, and non-toxic nature. This peroxiredoxin-2-derived peptide was synthesized, combined with a commercially available adjuvant, and used for vaccination. The test vaccine demonstrated a 60–70% protection rate against early-stage Lepeophtheirus salmonis infection in a challenge trial in Norway. Additionally, the vaccine was tested against salmon lice (Caligus rogercresseyi) in Chile, where a remarkable 92% reduction in the number of adult lice was observed. Thus, in combination with the selected adjuvant, the peptide showed antigenic potential, making it a suitable candidate for future vaccine development. The approach described holds promise for the development of peptide vaccines against various ectoparasites feeding on blood or skin secretions of their hosts. Full article

Adjuvants enhance immune responses stimulated by vaccines. To date, many seasonal influenza vaccines are not formulated with an adjuvant. In the present study, the adjuvant Advax-SM™ was combined with next generation, broadly reactive influenza hemagglutinin (HA) vaccines that were designed using a computationally optimized broadly reactive antigen (COBRA) methodology. Advax-SM™ is a novel adjuvant comprising inulin polysaccharide and CpG55.2, a TLR9 agonist. COBRA HA vaccines were combined with Advax-SM™ or a comparator squalene emulsion (SE) adjuvant and administered to mice intramuscularly. Mice vaccinated with Advax-SM™ adjuvanted COBRA HA vaccines had increased serum levels of anti-influenza IgG and IgA, high hemagglutination inhibition activity against a panel of H1N1 and H3N2 influenza viruses, and increased anti-influenza antibody secreting cells isolated from spleens. COBRA HA plus Advax-SM™ immunized mice were protected against both morbidity and mortality following viral challenge and, at postmortem, had no detectable lung viral titers or lung inflammation. Overall, the Advax-SM™-adjuvanted COBRA HA formulation provided effective protection against drifted H1N1 and H3N2 influenza viruses. Full article

Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) has infected more than 762 million people to date and has caused approximately 7 million deaths all around the world, involving more than 187 countries. Although currently available vaccines show high efficacy in preventing severe respiratory complications in infected patients, the high number of mutations in the S proteins of the current variants is responsible for the high level of immune evasion and transmissibility of the virus and the reduced effectiveness of acquired immunity. In this scenario, the development of safe and effective drugs of synthetic or natural origin to suppress viral replication and treat acute forms of COVID-19 remains a valid therapeutic challenge. Given the successful history of flavonoids-based drug discovery, we developed esters of substituted cinnamic acids with quercetin to evaluate their in vitro activity against a broad spectrum of Coronaviruses. Interestingly, two derivatives, the 3,4-methylenedioxy 6 and the ester of acid 7, have proved to be effective in reducing OC43-induced cytopathogenicity, showing interesting EC50s profiles. The ester of synaptic acid 7 in particular, which is not endowed with relevant cytotoxicity under any of the tested conditions, turned out to be active against OC43 and SARS-CoV-2, showing a promising EC₅₀. Therefore, said compound was selected as the lead object of further analysis. When tested in a yield reduction, assay 7 produced a significant dose-dependent reduction in viral titer. However, the compound was not virucidal, as exposure to high concentrations of it did not affect viral infectivity, nor did it affect hCoV-OC43 penetration into pre-treated host cells. Additional studies on the action mechanism have suggested that our derivative may inhibit viral endocytosis by reducing viral attachment to host cells. Full article

Cancer vaccines have emerged as a potent strategy to improve cancer immunity, with or without the combination of checkpoint blockade. In our investigation, liposomal formulations containing synthetic long peptides and α-Galactosylceramide, along with a DC-SIGN-targeting ligand, Lewis Y (Le^Y), were studied for their anti-tumor potential. The formulated liposomes boosted with anti-CD40 adjuvant demonstrated robust invariant natural killer (iNKT), CD4⁺, and CD8⁺ T-cell activation in vivo. The incorporation of Le^Y facilitated the targeting of antigen-presenting cells expressing DC-SIGN in vitro and in vivo. Surprisingly, mice vaccinated with Le^Y-modified liposomes exhibited comparable tumor reduction and survival rates to those treated with untargeted counterparts despite a decrease in antigen-specific CD8⁺ T-cell responses. These results suggest that impaired induction of antigen-specific CD8⁺ T-cells via DC-SIGN targeting does not compromise anti-tumor potential, hinting at alternative immune activation routes beyond CD8⁺ T-cell activation. Full article

The traditional manual recording of vaccination records in Germany faced challenges during the COVID-19 pandemic, prompting the introduction of a COVID smartphone app with QR codes. However, this solution brought new challenges, emphasizing the need for a centrally managed European digital vaccination record for efficiency and validity. This study assesses the feasibility of using the HL7 FHIR standard in the healthcare industry for implementing a digital vaccination pass management and monitoring system. The system aims to offer convenience and improved efficiency for both patients and healthcare providers while promoting interoperability with other healthcare systems. To this end, we developed a prototype using modern technologies, such as React, Quarkus, and Keycloak. Results indicate potential benefits for patients and healthcare providers, offering access to immunization records, personalized recommendations, and streamlined management. However, integrating nuanced vaccination processes into the standardized FHIR system requires custom extensions, which might hinder interoperability. Manual data entry and the integration of an identity provider present further obstacles in industry scenarios. Despite these challenges, this study suggests that implementing HL7 FHIR can enhance efficiency, data accessibility, and accuracy in the vaccination process, supporting broader digitization efforts in the German healthcare system and beyond. Full article

Group A Streptococcus (GAS) presents a significant global health burden due to its diverse clinical manifestations ranging from mild infections to life-threatening invasive diseases. While historically stable, the incidence of GAS infections declined during the COVID-19 pandemic but resurged following the relaxation of preventive measures. Despite general responsiveness to β-lactam antibiotics, there remains an urgent need for a GAS vaccine due to its substantial global disease burden, particularly in low-resource settings. Vaccine development faces numerous challenges, including the extensive strain diversity, the lack of suitable animal models for testing, potential autoimmune complications, and the need for global distribution, while addressing socioeconomic disparities in vaccine access. Several vaccine candidates are in various stages of development, offering hope for effective prevention strategies in the future. Full article

People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all p < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose (p > 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose (p = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables (p = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses (p < 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose (p = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection. Full article

In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body’s immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-β, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT’s antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections. Full article

Chronic obstructive pulmonary disease (COPD) is a common condition with an estimated prevalence of 12% in adults over the age of 30 years worldwide. COPD is a leading cause of morbidity and mortality globally, with a substantial economic and social burden. There are an estimated 3 million deaths annually due to COPD. However, most of the patients with COPD respond to routine interventions like bronchodilator therapy, assessing supplemental oxygen needs, smoking cessation, vaccinations, and pulmonary rehabilitation. There is a significant number of patients who unfortunately progress to have persistent symptoms despite these interventions. Refractory COPD is not yet formally defined. Patients with severe persistent symptoms or exacerbations despite appropriate care can be considered to have refractory COPD. Managing refractory COPD needs a multidimensional approach. In this review article, we will discuss essential interventions like ensuring adequate inhaler techniques, exploring the need for non-invasive ventilatory support, use of chronic antibiotics and phosphodiesterase inhibitors to advanced therapies like bronchoscopic lung volume reduction surgery, and the upcoming role of anti-IL5 agents in managing patients with refractory COPD. We will also discuss non-pharmacologic interventions like psycho-social support and nutritional support. We will conclude by discussing the palliative care aspect of managing patients with refractory COPD. Through this review article, we aim to better the approach to managing patients with refractory COPD and discuss new upcoming therapies. Full article

African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars, caused by African swine fever virus (ASFV). The development of cross-protective vaccines against ASF is imperative for effective disease control, particularly in regions where ASF is endemic, potentially featuring multiple circulating ASFV isolates. The investigation of non-hemadsorbing naturally attenuated isolates and laboratory recombinant strains with a deletion in the EP402R gene has attracted interest. Our study aimed to assess the impacts of various administration routes and doses of the naturally attenuated ASFV-PSA-1NH (immunotype IV, genotype I) isolate on the manifestation of clinical signs of ASF and the level of protection against the heterologous ASFV-Stavropol 01/08 strain (seroimmunotype VIII, genotype II). The results demonstrated that the intranasal administration of a low dose of ASFV-PSA-1NH to pigs minimized the clinical signs of ASF and established a high level of protection against the heterologous strain ASFV-Stavropol 01/08. Despite the challenges in standardizing the dosage for intranasal administration, this approach appears as a viable alternative in ASF vaccination. Full article

Altruism plays an essential role in promoting vaccine uptake, an issue that came to the fore during the COVID-19 pandemic through discussions of herd immunity and altruistic motivations. In response, the primary objective of this cross-sectional survey was to explore how altruistic attitudes have evolved in the post-pandemic era and to assess their effectiveness in motivating vaccination behavior in different age groups. The study aimed to elucidate changes in altruistic motivations for vaccination and their implications for public health strategies. Using a representative sample of the adult population of South Tyrol, Italy, including 1388 participants, altruism was assessed in 2023 with the scales of the Elderly Care Research Center (ECRC) and the International Personality Item Pool (IPIP) subscale of the version 5F30F-R1. Its association with demographic variables, vaccination attitudes and personal beliefs in two age groups (18–69 years, 70+ years) was analyzed. The results reveal distinct predictors of altruism across these scales and age groups, suggesting a shift in altruistic attitudes towards vaccination when comparing data from a similar survey conducted in 2021 with the 2023 results. Consequently, the use of altruism scales for different age groups is warranted. This study highlights the need for further research in this field. It concludes that while promoting altruistic behavior to increase vaccine uptake appears to be effective primarily among the younger population, emphasizing personal safety is more appropriate for encouraging vaccination among older individuals. Full article

The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface O-glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA^- like substances (HBGA⁺) capable of binding RV particles in vitro. We hypothesized that HBGA⁺ bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA⁺ or HBGA^- bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA⁺ bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA^- bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA⁺ bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA⁺ bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs. Full article

Background/Objectives: This study aimed to investigate the association between colorectal cancer (CRC) and the risk of breakthrough respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated patients with CRC. Methods: This retrospective cohort study used the TriNetX research network to identify vaccinated patients with CRC. Patients were matched using propensity score matching (PSM) and divided into patients with CRC and control (without history of CRC) groups. The primary outcome was the risk of breakthrough SARS-CoV-2 in vaccinated patients. The secondary outcome was a composite of all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period after the diagnosis of COVID-19. Results: A total of 15,416 vaccinated patients with CRC were identified and propensity matched with 15,416 vaccinated patients without CRC. Patients with CRC had a significantly increased risk for breakthrough infections compared to patients without CRC (aOR = 1.78; [95% CI: 1.47–2.15]). Patients with CRC were at increased risk of breakthrough SARS-CoV-2 infections after two doses (aOR = 1.71; [95% CI: 1.42–2.06]) and three doses (aOR = 1.36; [95% CI: 1.09–1.69]) of SARS-CoV-2 vaccine. Vaccinated patients with CRC were at a lower risk of COVID-19 infection than unvaccinated CRC patients (aOR = 0.342; [95% CI: 0.289–0.404]). The overall composite outcome (all-cause ED visits, all-cause hospitalization, and all-cause death) was 51.6% for breakthrough infections, which was greater than 44.3% for propensity score-matched patients without CRC (aOR = 1.79; [95% CI: 1.29–2.47]). Conclusions: This cohort study showed significantly increased risks for breakthrough SARS-CoV-2 infection in vaccinated patients with CRC. Breakthrough SARS-CoV-2 infections in patients with CRC were associated with significant and substantial risks for hospitalizations. Full article

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38–0.43) and OR = 0.15 (95% CI, 0.11–0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12–0.15) and OR (for severe disease) = 0.02 (0.01–0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19–2.10), p = 0.001 and 1.25 (1.03–1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes. Full article