Search Results (567)

Despite the widespread accessibility of vaccines and antivirals, seasonal influenza virus epidemics continue to pose a threat to public health. In this study, we constructed a recombinant replication-deficient simian adenovirus type 25 vector carrying the full-length hemagglutinin (HA) of the H1N1 influenza virus, named rSAd25-H1. Both systemic and mucosal humoral immune responses, as well as the protective efficacy, were assessed in mice immunized via the intramuscular (IM) or intranasal (IN) route. A single-dose IM or IN administration of rSAd25-H1 elicited a robust systemic IgG antibody response, including hemagglutination inhibition antibodies. As expected, only IN immunization was able to induce IgA production in serum and respiratory mucosa. Notably, a single dose of rSAd25-H1 at the highest dose (10¹⁰ viral particles) conferred complete protection against lethal homologous H1N1 challenge in mice despite the route of administration. These findings demonstrate the potential of simian adenovirus type 25-based vectors as a promising candidate for intranasal vaccine development targeting respiratory pathogens. Full article

This study aimed to estimate the end-of-season influenza vaccine effectiveness (VE) for the 2024/25 season in Beijing, China. Methods: We used a test-negative design (TND) to assess influenza VE among outpatients with influenza-like illness (ILI) enrolled through the influenza virological surveillance in sentinel hospitals in Beijing from week 44, 2024 to week 14, 2025. Cases were ILI patients who tested positive for influenza; controls were those who tested negative. Results: Among 18,405 ILI patients tested, 3690 (20.0%) were positive for influenza, with A(H1N1)pdm09 as the predominant strain (98.9%). The overall influenza vaccination coverage was 12.4%. Adjusted VE was 48.3% (95%CI: 40.4%–55.3%) against any influenza and 48.2% (95%CI: 40.3%–55.1%) against A(H1N1)pdm09, with the highest VE observed in adults aged 18–59 years (79.0%). The adjusted VE was similar for those vaccinated in 2023/24 only (53.1%) or both 2023/24 and 2024/25 seasons (50.8%), but lower for those vaccinated only in the 2024/25 season (48.5%). The adjusted VE was higher during the epidemic period (52.5%) than in the pre-epidemic (48.1%) and post-epidemic (35.3%) periods. Conclusions: Our findings indicate moderate VE against laboratory-confirmed influenza, especially A(H1N1)pdm09, during the end of the 2024/25 season in Beijing, China. Influenza vaccination provided protective effects across different epidemic periods. These timely estimates support ongoing public health communication and immunization strategies. Full article

Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, Ligilactobacillus salivarius LSM231, and Lactiplantibacillus plantarum LPM239, which exhibited synergistic growth, potent acid/bile salt tolerance, and broad-spectrum antimicrobial activity against pathogens. In vitro, the probiotic combination disrupted pathogen ultrastructure and inhibited PEDV replication in IPI-2I cells. In vivo, PEDV-infected piglets administered with the multi-strain probiotic exhibited decreased viral loads in anal and nasal swabs, as well as in intestinal tissues. This intervention was associated with the alleviation of diarrhea symptoms and improved weight gain. Furthermore, the multi-strain probiotic facilitated the repair of intestinal villi and tight junctions, increased the number of goblet cells, downregulated pro-inflammatory cytokines, enhanced the expression of barrier proteins, and upregulated antiviral interferon-stimulated genes. These findings demonstrate that the multi-strain probiotic mitigates PEDV-induced damage by restoring intestinal barrier homeostasis and modulating immune responses, providing a novel strategy for controlling PEDV infections. Full article

Water temperature significantly affects the physiological balance of aquatic organisms like crustaceans, and heat shock proteins (HSPs) are crucial for stress resistance and pathogen defense. This study conducted a genome-wide analysis to explore the functional characteristics of the Hsp70 gene family in Procambarus clarkii. Fifteen Hsp70 family members were identified, with several genes showing upregulation under non-lethal heat shock (NLHS) and pathogen challenges. RNA-Seq and qPCR analyses confirmed increased expression of certain PcHsp70s during NLHS, indicating NLHS activation of the Hsp70 family to enhance immune regulation. dsRNA-mediated silencing of Hsp70 led to downregulation of TLR pathway genes (e.g., TLR1, TLR6), suggesting Hsp70 regulates the TLR signaling pathway for immune responses. These findings reveal that NLHS-induced Hsp70 upregulation improves pathogen resistance, offering insights for addressing temperature fluctuations and disease outbreaks in aquaculture to optimize management practices. Full article

Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 10⁰ copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article

Heart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF include oxidative stress, microvascular dysfunction, and chronic unresolved inflammation. Our lab focuses on oxidative stress-mediated cellular dysfunction, particularly the toxic effects of lipid peroxidation products like 4-hydroxy-2-nonenal (4HNE). Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a vital role in detoxifying 4HNE and thereby protecting the heart against pathological stress. ALDH2 activity is reduced in various metabolic stress-mediated cardiac pathologies. The dysfunction of coronary vascular endothelial cells (CVECs) is critical in initiating HFpEF development. Thus, we hypothesized that ectopic overexpression of ALDH2 in CVECs could mitigate metabolic stress-induced HFpEF pathogenesis. In this study, we tested the efficacy of intracardiac injections of the ALDH2 gene into CVECs in db/db mice—a model of obesity-induced type 2 diabetes mellitus (T2DM)—and their controls, db/m mice, by injection with ALDH2 constructs (AAV9-VE-cadherin-hALDH2-HA tag-P2A) or control constructs (AAV9-VE-cadherin-HA tag-P2A-eGFP). We found that intracardiac ALDH2 gene transfer increased ALDH2 levels specifically in CVECs compared to other myocardial cells. Additionally, we observed increased ALDH2 levels and activity, along with decreased 4HNE adducts, in the hearts of mice receiving ALDH2 gene transfer compared to control GFP transfer. Furthermore, ALDH2 gene transfer to CVECs improved diastolic function compared to GFP control alone. In conclusion, ectopic ALDH2 expression in CVECs can contribute, at least partially, to the amelioration of HFpEF. Full article

The aim of this study was to determine the level of anti-hemagglutinin antibodies using the hemagglutination inhibition test (HAI) in the blood sera of patients collected during the 2023/2024 epidemic season in Poland. This data is valuable for assessing the level of population immunity to influenza viruses circulating in Poland during this epidemic season. The study material consisted of serum samples collected across the country and divided into seven age groups. The test results confirmed the presence of anti-hemagglutinin antibodies for the antigens included in the quadrivalent influenza vaccine recommended by the World Health Organization (WHO) for the 2023/2024 epidemic season: A/Victoria/4897/2022 (H1N1)pdm09, A/Darwin/9/2021 (H3N2), B/Austria/1359417/2021 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage). The highest values of the geometric mean (GMT = 121.0 [95% CI: 108.5–134.9]) and protective factor (70 [95% CI: 67–74]%) were recorded for the A/H3N2/influenza virus antigen. In Poland, the vaccination rate of the general population in the discussed season was only 5.52%. The obtained results can therefore be interpreted as a response of the immune system, consisting of the production of anti-hemagglutinin antibodies in patients who had previously had an infection caused by the influenza virus. Full article

The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients. Full article

The pine wood nematode (Bursaphelenchus xylophilus, PWN) is a globally significant quarantine pest that causes severe economic and ecological damage to coniferous forests worldwide. Additionally, PWNs continue to expand into higher latitudes. However, studies on their cold tolerance remain limited. This study investigated the overwintering environment of PWNs in epidemic areas of Liaoning Province, China. It established a protocol to induce anhydrobiosis in PWNs, evaluated their low-temperature resistance, observed morphological changes during anhydrobiosis, and explored potentially involved key genes. The results showed that (1) there was no significant difference in thermal insulation between infected and healthy wood in Liaoning Province; both effectively reduced temperature fluctuation rates, providing a protective function for PWN overwintering. (2) PWNs significantly enabled their cold tolerance through anhydrobiosis, accompanied by significant morphological changes and substantial lipid droplet depletion. (3) Eleven anhydrobiosis-related genes were identified. Among these, the collagen gene family showed consistent expression patterns throughout dehydration and rehydration. This suggests a potential role in cuticle structural changes and osmoregulation during anhydrobiosis. These findings provide a theoretical basis for understanding how PWNs survive winter conditions in high-latitude regions. Additionally, they offer valuable insights for future research into PWN anhydrobiosis and the development of effective control strategies. Full article

Background: Measles, an acute respiratory infectious disease caused by the measles virus, continues to pose a significant threat to children under five years old worldwide. Despite the availability of effective vaccines, challenges such as insufficient vaccination coverage and antigenic drift contribute to its persistence. Based on a newly isolated wild-type measles virus strain (genotype H1a), designated MVs/Jiangsu.CHN/38.16/1[H1a] (MV-1), this study aims to develop and evaluate a novel recombinant measles virus vaccine candidate designed to enhance immunogenicity and broaden protection against multiple epidemic genotypes. Methods: A recombinant measles virus vaccine candidate, designated rSchwarz/FH(H1a), was developed by incorporating immunogenic genes from the H1a genotype into the backbone of the Schwarz vaccine strain. The genetic stability, safety, and immunogenicity of this vaccine candidate were evaluated in preclinical models. Relevant sample sizes and methodologies were selected to ensure comprehensive assessment of vaccine efficacy against various genotypes (H1a, B3, D8). Results: The rSchwarz/FH(H1a) vaccine candidate demonstrated enhanced immunogenicity, with robust immune responses observed against the targeted genotypes. Additionally, it showed excellent genetic stability and safety profiles, indicating potential for effective use in vaccination programs. Notably, the vaccine provided cross-protection against multiple epidemic genotypes, highlighting its broader application in controlling measles outbreaks. Conclusions: Our findings suggest that the rSchwarz/FH(H1a) vaccine candidate represents a promising advancement in measles vaccine development. It has the potential to strengthen current measles vaccination strategies by providing improved immunogenicity and broader protection against different circulating genotypes. Further clinical trials are warranted to confirm these promising preclinical results. Full article

Background: Given the significant impact of population immunity on the measles epidemic, understanding immunity differences among populations with varying immunity backgrounds is necessary for identifying immunity gaps and informing vaccination policies. In this study, we aimed to determine the distinct dynamics of vaccine-induced and naturally acquired antibodies, with specific focus on difference in vaccine-induced antibody responses across different birth cohorts. Methods: Based on two cohorts and one cross-sectional study conducted in Anhua County, Hunan Province, China, serum samples from children who followed China’s routine measles vaccination schedule (i.e., two-dose schedule at 8/18 months) and adults who acquired immunity through natural infection were tested for measles IgG antibodies using an enzyme-linked immunosorbent assay. The generalized additive mixed model and a mechanistic model were employed to describe antibody dynamics following vaccination and infections. Wavelet analysis was used to investigate the temporal relationship between the measles epidemic and long-term antibody levels after natural infection. Results: A total of 408 children (0–12 years) and 222 adults (54–84 years) were included in the present study. Vaccine-induced antibody levels following 8 m/18 m vaccination were estimated to fall below the protective threshold of 200 mIU/mL by age of 15.8, whereas antibody levels following infections remained high. The decay rate of vaccine-induced antibodies was estimated at 3.0 × 10⁻³ log-log mIU/mL per year, whereas naturally acquired measles antibodies persisted lifelong with a significantly lower decay rate of 2.30 × 10⁻⁵ log-log mIU/mL per year. Moreover, vaccine-induced antibody levels in children born after 2010—a period of low measles incidence—declined more rapidly (duration of protective immunity: 12.5 years), compared to those born before 2010. Discussion: Our findings revealed immunity heterogeneity among individuals with difference measles immunity backgrounds. In particular, the birth-cohort specific differences in vaccine-induced immunity highlighted the key role of young generations born in settings with low measles incidence in contributing to population immunity gaps. This underlines that greater attention should be given to this group in future catch-up vaccination efforts. Full article

Feline panleukopenia (FPL), caused by the feline panleukopenia virus (FPLV), is a severe and highly contagious viral disease with high morbidity and mortality. Vaccination remains the gold standard for preventing and controlling this debilitating condition. The viral protein VP2 serves as the major immunogen of FPLV and represents the key target antigen in the development of a novel FPLV vaccine. Virus-like particle (VLP)-based vaccines have emerged as next-generation vaccine candidates due to their high immunogenicity and safe profile. In this study, a baculovirus expression vector system (BEVS) was employed to generate FPLV-VLPs through recombinant expression of the VP2 protein of a Chinese epidemic strain (Ala91Ser, Ile101Thr) of FPLV. The resulting FPLV-VLPs demonstrated markedly enhanced antigenicity and hemagglutination activity, achieving a hemagglutination titer of up to 1:2¹⁶. Following vaccination, immunized cats developed high titers of anti-FPLV hemagglutination inhibition (HI) antibodies (1:2¹⁶) and exhibited 100% protection against challenge with a virulent epidemic FPLV variant (Ala91Ser, Ile101Thr). These findings demonstrate that FPLV-VLPs hold strong potential as candidates for a novel subunit vaccine against FPLV infection. Full article

The growing epidemic of childhood obesity is a major threat to their overall development and poses a number of challenges for health systems. We propose an integrated framework to comprehensively address childhood obesity. The proposed architecture addresses essential data management and pre-processing functionalities to support scalable, secure, and privacy-preserving data processing in distributed environments. We are also incorporating a health data-driven AI approach for predictive analytics and decision support. There is additionally a User Engagement Layer, which serves as the main point of interaction for users. It connects individuals to system capabilities, facilitating data collection, progress monitoring, and insights. Finally, we present four serious games designed to address protective factors (such as physical activity and healthy eating) and mitigate risk factors (such as excessive screen time and unhealthy food choices). The identified educational objectives were translated into game elements including goal setting, social support, and positive reinforcement. In order to facilitate our approach, we have described the essential data flows and user interactions within our Biobank architecture. Full article

Porcine epidemic diarrhea virus (PEDV), the etiology of porcine epidemic diarrhea (PED), continues to impose severe economic burdens on pig farms in China. The continuous emergence of new variant strains makes it difficult for vaccinated sows to provide protective immunity to piglets. Hence, there is an urgent need for efficacious therapeutic drugs in clinical practice. In the present study, the antiviral activity of GS-441524, a nucleoside analogue, against PEDV was evaluated. It can efficiently inhibit the proliferation of trypsin-dependent and trypsin-independent PEDVs in a dose-dependent manner, exhibiting greater efficacy against the trypsin-independent strain. GS-441524 can inhibit trypsin-independent PEDV proliferation in Vero cells with EC₅₀ and CC₅₀ values of 2.6 μM and 104.4 μM, respectively. As expected, GS-441524 exerts its inhibitory effect during the replication phase of the four stages of the PEDV proliferation cycle. Even at a high viral infection dose of MOI 0.5 or added 6 h post-viral infection, 20 μM GS-441524 can still effectively inhibit PEDV proliferation. These findings emphasize the potent antiviral activity of GS-441524 against PEDV, and its therapeutic efficacy on PEDV-infected piglets warrants further investigation. Full article

Flaviviruses are a group of viruses transmitted mainly by mosquitoes and ticks, causing severe diseases in humans. Examples include dengue, Zika, West Nile virus, and yellow fever. They primarily affect individuals in tropical and subtropical regions, causing public health problems such as epidemic outbreaks and significant economic burdens due to hospitalizations and treatments. They share antigens, leading to cross-reactivity where antibodies generated against one flavivirus can react with others, complicating the accurate diagnosis of individual infections and making the development of treatments or vaccines more challenging. The role of T cells in the immune response to flaviviruses is a complex topic debated by scientists. On one hand, T cells help control infection by eliminating infected cells and protecting against disease. However, there is evidence that an excessive or dysregulated T cell response can cause tissue damage and worsen the disease, as seen in severe dengue cases. This duality underscores the complexity of the immune response to flavivirus infections, posing a significant challenge for researchers. Gaining a deeper understanding of the immune response at the cellular level, particularly the role of T follicular helper cells, can reveal new avenues of investigation that could lead to novel strategies for disease management. This review explores the dynamics of T cell responses, focusing on circulatory T follicular helper cells (cT_FH), to enhance our understanding of flavivirus immunity and inform future interventions. Full article