Search Results (1,088)

Background/Objectives: Classical swine fever (CSF) and pseudorabies (PR), caused by classical swine fever virus (CSFV) and pseudorabies virus (PRV) respectively, are economically significant viral diseases worldwide that severely compromise swine health and constrain international trade. Previously, we generated a recombinant PRV (rPRVTJ-UL44-E2) expressing the CSFV E2 protein that elicited rapid E2-specific antibody responses in rabbits as early as 7 days post-immunization (dpi). However, its immunogenicity and protective efficacy in pigs remain uncharacterized. In this study, we evaluated the protective performance of rPRVTJ-UL44-E2 in pigs via needle-free immunization. Methods: Pigs (n = 5) received a prime immunization with 10⁷ median tissue culture infective doses (TCID₅₀) of rPRVTJ-UL44-E2 via needle-free immunization, followed by a boost immunization with the same dose at 21 dpi, and were then challenged with 10⁵ TCID₅₀ of the virulent CSFV Shimen strain (CSFV-SM) at 33 dpi. Results: Pigs immunized with rPRVTJ-UL44-E2 developed E2-specific antibodies (blocking rates > cutoff value (40%) at 25 dpi) and gB-specific antibodies that were detectable as early as 7 dpi, with anti-CSFV neutralizing antibody titers comparable to those induced by the C-strain vaccine and anti-PRV neutralizing antibody titers also reaching detectable levels at 28 dpi, whereas no specific antibodies were detected in the DMEM control group. All pigs immunized with rPRVTJ-UL44-E2 and C-strain survived the lethal CSFV challenge with no clinical signs or detectable viremia. In contrast all DMEM control pigs succumbed to infection within 9 days post-challenge (dpc). Conclusions: These findings demonstrate that needle-free delivery of rPRVTJ-UL44-E2 confers complete protection against lethal CSFV challenge in pigs. Full article

Conventional needle-based vaccination may cause tissue injury and increase the risk of cross-contamination between animals. This study evaluated the immunological effects of delivering an inactivated porcine circovirus type 2 (PCV2) vaccine using a needle-free jet injection system compared with needle injection in pigs. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) for PCV2-specific antibody levels on days 7, 14, and 28 post-vaccination. Cellular architecture at injection sites and differential gene expression were analyzed using immunohistochemistry and transcriptome sequencing. Results showed that pigs receiving needle-free vaccination at 0.50 mL and 0.75 mL injection volumes exhibited higher PCV2-specific antibody responses than pigs receiving 1.0 mL needle injection. Needle-free vaccination also preserved dermal collagen fiber architecture, altered antigen-presenting cell distribution, and was associated with distinct activation of immune-related pathways, particularly those involved in leukocyte migration and cytokine-cytokine receptor interactions. These findings indicate that needle-free vaccination was associated with distinct PCV2-specific antibody responses and local immune microenvironment changes, supporting its potential as an alternative vaccine delivery strategy for swine PCV2 vaccination. Full article

Human immunodeficiency virus (HIV) is an enveloped virus with a remarkable capacity for genetic diversification, enabling rapid escape from host immune responses and therapeutic interventions. Despite extensive global efforts, the development of an effective vaccine has remained elusive owing to the virus’s high genetic variability and antigenic diversity. Consequently, considerable effort has been directed toward the development of therapeutic agents targeting viral entry, reverse transcriptase, integrase, protease, and more recently, capsid. Although antiretroviral therapy (ART) remains the cornerstone of HIV treatment, it is associated with challenges including drug resistance, adverse side effects, and limitations in access and affordability. Targeting viral entry offers distinct advantages by blocking infection at the earliest stage of the viral life cycle and enabling the neutralization of free virions, as well as Fc-mediated elimination of HIV-infected cells in some cases. This review highlights promising protein-based HIV entry inhibitors that have demonstrated efficacy in preclinical studies, and discusses ongoing efforts to optimize their valency, avidity, specificity, serum half-life, effector functions, and production platforms to improve their therapeutic potential and economic feasibility. Full article

Background: Staphylococcus aureus (SA) causes septicemia and arthritis, eventually resulting in substantial economic losses and health hazards in poultry. Lethal electron beam (eBeam) treatment kills bacteria while preserving surface epitopes. Methods: This study compared broiler chicken immune responses (local and systemic) after eBeam-killed (eB) or formalin-killed (FK) SA injections. The vaccine (sham) control was endotoxin-free PBS. This study contained six treatments (trt) with five chickens/trt, with vaccine trts divided into two groups, A and B. Group A received in ovo vaccine/sham treatments (phase 1) initially. At 34 d of age, the pulps of growing feathers (GFs) received intradermal (i.d.) injections of the respective trt to elicit booster and primary responses in groups A and B, respectively. Blood was collected to analyze leukocyte populations and plasma SA-specific antibody levels. Additionally, in phase 2, GFs were collected to assess leukocyte presence in GF pulps. Two-way ANOVA was conducted to test the effects of treatment, time, and their interactions, followed by Tukey’s HSD tests at p < 0.05 for statistical significance. Results: Early in phase 1, the eB group had increased SA-specific IgM, IgA, and total lymphocyte concentrations compared with FK. In phase 2, FK and eB i.d. vaccines increased total lymphocyte and T cell proportions in GF pulps compared with sham. In blood, the recall eB vaccination increased monocytes, B cells, CD8+ T cells, and total lymphocytes, while the recall FK vaccination increased heterophils (p < 0.05). Conclusions: Improved early protection at mucosal surfaces may be reflected by higher plasma levels of SA-specific IgM and IgA following in ovo eBeam-killed-SA vaccination. Additionally, both eB-SA and FK-SA vaccines stimulated robust local inflammatory responses dominated by lymphocytes in GF pulps. Full article

Many epidemiological models assume either closed populations or continuous demographic turnover. We consider an intermediate setting in which exchange occurs through discrete pulses. In this paper, we introduce a population-conserving compartmental epidemiological model with pulse population exchange at a set of prescribed times. At each pulse, a fraction of the population in each compartment is replaced by a combination of susceptible and immunized individuals. In contrast to typical pulse birth or pulse vaccination models where only a single compartment undergoes a pulse population change, the pulses in this model have competing effects: removing infectious individuals reduces the force of infection, while introducing new susceptibles increases it. In addition, when some part of the incoming population is immunized, the net effect of pulses becomes state-dependent. After presenting the model, we prove both conservation of total population and non-negativity in each compartment. We then show that while the non-pulsed system has only the disease-free equilibrium, the demographic changes introduced by the pulses can produce two new types of solution: a pulse-periodic endemic equilibrium and a second wave of infection. We derive an exact expression for a post-pulse endemic equilibrium in terms of the integrals of the solutions between equispaced pulses using the Poincaré map. Next, we identify the exact threshold at which the pulse-induced reduction in the susceptible population changes sign. Above the threshold, the pulses in all compartments contribute to a net reduction in the force of infection. Below this threshold, competing effects take hold—incoming susceptible individuals replenish the susceptible compartment, while departing exposed and infectious individuals no longer contribute to secondary infections. Finally, using parameters motivated by recent outbreaks of disease on cruise ships, we characterize this threshold mechanism and investigate the effect of pulse start time on the solution trajectories. Full article

Background: The interaction between COVID-19 vaccination and immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) remains incompletely characterized. Methods: Retrospective cohort study of 139 patients with stage IV NSCLC treated with first-line ICI-based therapy, stratified by vaccination status and total doses received (0–1 vs. ≥2). Progression-free (PFS) and overall survival (OS) were analyzed by Kaplan–Meier and Cox regression; logistic regression explored factors associated with treatment-related toxicity. Results: Vaccinated patients had longer median PFS (13.0 vs. 11.0 months) and OS (29.0 vs. 24.0 months; both p < 0.001). In multivariable models these associations were attenuated and of borderline significance (OS HR = 0.83, 95% CI 0.69–0.99; PFS HR = 0.79, 95% CI 0.62–0.99). Outcomes were also more favorable with ≥2 doses (median PFS 14.0 vs. 12.0 months, p = 0.001; median OS 30.0 vs. 24.0 months, p < 0.001), and tumor mutational status was the strongest independent predictor of survival. In an exploratory model, ≥2 doses were associated with higher odds of any-grade toxicity (OR = 2.47, p = 0.037); events were predominantly low grade, with no Grade 4 or 5 toxicity. Conclusions: COVID-19 vaccination was associated with improved PFS and OS in stage IV NSCLC receiving first-line ICI therapy, with a dose-related pattern. The association was attenuated after adjustment for tumor biology and is hypothesis-generating. These findings support the safety and potential clinical relevance of vaccination in this population and underline the need for structured monitoring during immunotherapy. Prospective validation is required. Full article

Background/Objectives: Pseudorabies virus (PRV) variant strains have caused widespread outbreaks in China since 2011, and currently available vaccines provide suboptimal protection. Glycoprotein D (gD), the principal target of virus-neutralizing antibodies, represents a promising antigen for subunit vaccine development. However, CHO cell-based production systems suitable for large-scale manufacturing remain insufficiently explored. This study aimed to develop a potentially scalable CHO cell-derived PRV gD subunit vaccine and evaluate its immunogenicity and protective efficacy in mice. Methods: A stable Chinese hamster ovary (CHO) suspension cell line secreting the extracellular domain of PRV gD was established through signal peptide optimization and stepwise serum-free adaptation. The recombinant gD protein was purified using Ni²⁺- Sepharose High-Performance affinity chromatography and subsequently formulated with MONTANIDE ISA 206 adjuvant. Immunogenicity and protective efficacy were assessed in BALB/c mice through serological analysis, neutralization assays, lethal challenge experiments, and quantitative PCR. Results: The gD subunit vaccine induced rapid seroconversion of gD-specific IgG antibodies as early as 7 days post immunization and exhibited a strong booster effect, maintaining high antibody levels. Neutralizing antibodies were first detected at 14 days and increased significantly after booster immunization, with titers markedly exceeding those induced by a commercial inactivated PRV vaccine at 42 days (p = 0.001). Following lethal challenge with 10⁴ TCID₅₀ of the highly virulent PRV-TJ variant strain, vaccinated mice achieved 100% survival without clinical signs. Viral genome copy numbers in the brain and spinal cord were reduced by approximately 3.3 to 4.4 log₁₀ relative to the PBS control group. Conclusions: The CHO cell-derived PRV gD subunit vaccine elicits robust humoral immune responses and provides complete protection against lethal PRV variant challenge in mice. These findings support its further evaluation in the natural swine host toward the development of a safe and scalable subunit vaccine for pseudorabies control. Full article

Gyrovirus homsa1 (GyH1) causes immunosuppression and multi-organ damage in young poultry. The VP1 capsid protein (VP1) is a key target for subunit vaccine development; however, recombinant VP1 alone elicits limited immunogenicity and requires an efficient delivery system. Here, we developed a liposomal formulation associated with the GyH1 VP1 protein (LNP-VP1) and evaluated its immunogenicity and preliminary safety in specific-pathogen-free chickens. The prepared LNP-VP1 had a mean particle size of 230.11 ± 5.95 nm, a polydispersity index of 0.204 ± 0.023, a zeta potential of −36.55 ± 0.99 mV, and an apparent encapsulation efficiency of 84.03% ± 2.10%. In addition, immunization of chicks with LNP-VP1 induced robust antigen-specific IgG responses and significantly enhanced the infiltration of CD4⁺ and CD8⁺ T cells in the spleen. Furthermore, cytokine analysis revealed upregulation of IFN-γ, IL-4, and IL-17 levels following vaccination. Importantly, no vaccine-associated histopathological changes were observed in major immune or metabolic organs after immunization. Overall, LNP-VP1 effectively elicited both humoral and cellular immune responses with a favorable safety profile, indicating its potential as a candidate vaccine against GyH1 and providing experimental evidence supporting lipid nanoparticles as a delivery platform for avian subunit vaccines. Full article

Wildlife reservoirs sustain rabies transmission despite vaccination of domestic animals, highlighting the need for oral rabies vaccination strategies adapted to contrasting ecological settings. We conducted a pilot multi-region field evaluation of a locally developed briquette-formulated oral rabies vaccine bait at purposively selected sites in four regions of Kazakhstan during 2025–2026. Overall, 9256 baits were deployed, including 4556 placed manually and 4700 distributed by aircraft. Among the manually monitored baits, apparent uptake was 57.2% (2604/4556) and ranged from 11.3% to 75.3% among region-campaign groups. Recovered baits retained their structural integrity following a controlled aerial test drop. Tetracycline fluorescence was detected in seven of ten free-ranging foxes, and six had rabies virus-neutralising antibody titres of ≥0.5 IU/mL. Following controlled oral administration of a single bait, all six initially seronegative captive red foxes and four of five captive raccoons met the predefined seroconversion criterion. These findings support the operational field feasibility of the briquette-formulated bait across contrasting selected landscapes and demonstrate oral immunogenicity under controlled conditions. The observed variation in apparent uptake indicates that bait distribution strategies should be adapted to local wildlife ecology and deployment conditions. Full article

This work constructs, analyzes and simulates a new general SIR epidemiological model for the spread of a generic long-time disease, in which the coefficients of infectivity and death rate are system variables. Diseases, such as COVID-19, have demonstrated clearly that infectivity and death rates can change over time, even for the same variant of the virus, due to vaccination, improved treatments, better analysis, better medications, etc. This motivates us to construct the SIR-ID model for a generic disease in which the rate coefficients are state variables as a part of the systems’s evolution in time. The model consists of a coupled system of five differential equations, where the equations for the infectivity and death rate have general source functions. The analysis shows the existence, positivity and boundedness of the solutions. A discussion of the Endemic (EE) and Disease-Free (DFE) equilibria and their stability is provided. A bifurcation analysis of the DFE and EE is conducted, as well as a sensitivity analysis. Then, computer simulations depict two typical cases of dynamic behavior, one when the DFE is stable and attracting, and one in which the EE is stable and attracting. These also show the way the system approaches the steady states. Full article

Breast cancer treatment still faces challenges including local recurrence, systemic toxicity, tumor heterogeneity, drug resistance, and immunosuppression. Conventional systemic administration provides limited exposure at the tumor site and exhibits significant toxicity. Injectable hydrogels, combining the properties of minimally invasive administration, in situ gelation, local retention, and sustained release, have become a key platform for local precision drug delivery. Compared with nanomedicines or free drugs, hydrogels can both prolong drug retention time and achieve on-demand release through the modulation of crosslinking density, degradation rate, and responsive chemical bonds. This review is organized around the material logic of such systems. Injectable hydrogels are first classified into natural, synthetic, hybrid, supramolecular, nanocomposite, and self-healing systems, the in situ gelation chemistries available to each are compared, and network parameters such as crosslinking density, mesh size, swelling, porosity, modulus, and rheology are related to release kinetics and intratumoral retention. Current research is primarily advancing along two directions: one is the construction of pH-, enzyme-, redox/ROS-, hypoxia-, ATP-, glucose-or thermo-responsive hydrogels; the other is achieving active targeting by integrating functionalized hydrogels with targets such as CD44, folate receptor, integrins, EGFR, transferrin receptor, and HER2 or with biomimetic cell-membrane coatings. On this basis, hydrogels have been extended to cancer vaccines, immune checkpoint modulation, local delivery of CAR-T/CAR-NK, as well as combination therapies involving chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, sonodynamic therapy, radiosensitization, gene therapy, and theranostics. The constraints imposed on hydrogel design by different payload classes, including small molecules, natural products, proteins and peptides, nucleic acids, antibodies, exosomes, and gene-editing machinery, are further examined, and imaging-integrated theranostic gels are discussed together with the emerging role of machine learning and digital fabrication in hydrogel optimization. Based on the biological foundations of breast cancer, this review summarizes advances in the material design, microenvironment-responsive release, targeting strategies, immunomodulation, and combination therapy of hydrogels, critically evaluates the limitations of each strategy, and aims to provide a reference for the design of mechanistically well-defined and translatable hydrogel delivery systems for breast cancer. Full article

H7N9 avian influenza virus (AIV) poses a persistent threat to poultry and public health. Despite widespread vaccination in China, rapid antigenic drift and reassortment necessitate frequent updates of vaccine strains. Phylogenetic analysis of isolates from Chinese provinces (from 2019 to 2023) showed that while surface genes diversified, the internal gene cassette remained conserved yet actively reassorted with other subtypes, suggesting internal gene compatibility may influence vaccine performance. We selected the H7N9 strain A/chicken/Northeast China/19854-6/2019 (E2), which harbors a polybasic Hemagglutinin (HA) cleavage site and predicted dual receptor-binding affinity. To enable safe vaccine development, we modified the HA cleavage site to generate a low-pathogenicity strain (E2-Δ). Using reverse genetics, we constructed three recombinant viruses: E2-Δ (retaining contemporary internal genes), CVI-E2, and CVII-E2 (containing internal genes from commercially used donor strains CVI and CVII, respectively). Inactivated vaccines were evaluated in specific-pathogen-free (SPF) chickens. E2-Δ induced HI antibody titers comparable to those of CVI-E2 and significantly higher than those of CVII-E2, and showed modestly higher cross-reactive HI titers against some recent H7N9 variants in exploratory analyses. All vaccines provided complete homologous protection with reduced viral shedding and no clinical signs in challenge trials. Our findings suggest that internal gene backbone compatibility may influence vaccine immunogenicity. While E2-Δ outperformed CVII-E2, it was comparable to CVI-E2, indicating that certain traditional backbones may still be suitable for H7N9 vaccine development. This approach warrants further validation to support a refined vaccine design strategy for H7N9 and potentially other avian influenza subtypes. Full article

Co-infection between influenza and Streptococcus pneumoniae is an important public health concern, since influenza can increase susceptibility to secondary bacterial invasion and enhance bacterial transmission. We develop and analyze a compartmental model of influenza–pneumococcal co-infection with eleven epidemiological compartments, incorporating imperfect vaccination, quarantine, and a three-stage pneumococcal progression from colonization to invasive disease. We establish the positivity and boundedness of solutions, determine the equilibria, and derive, via the next-generation matrix method, the sub-model reproduction numbers $R_0^I$ and $R_0^P$ together with the composite threshold $R_0=max\{R_0^I,R_0^P\}$. Each single infection undergoes a forward bifurcation: the disease-free equilibrium is locally asymptotically stable when the corresponding reproduction number is below unity, and a unique endemic equilibrium—globally asymptotically stable in the pneumococcal sub-model, established by a Goh–Volterra Lyapunov function—emerges above it. When both thresholds exceed unity, the two infections compete for the shared susceptible pool and undergo competitive exclusion: one infection persists while the other, together with the co-infected class, is eliminated. We show that the outcome is governed not by the disease-free reproduction numbers but by the invasion reproduction numbers evaluated at the single-infection boundary equilibria, so that even equal disease-free thresholds do not yield coexistence. Numerical simulations confirm the analytical results and quantify the effect of quarantine and vaccination, providing a framework for assessing control of interacting respiratory infections. Full article

Inclusion body hepatitis (IBH), a disease predominantly associated with fowl adenovirus serotypes 8a (FAdV-8a) and 8b (FAdV-8b), poses a significant challenge to poultry production on a global scale. This study reports a severe outbreak of IBH that occurred in 2021 at a chicken layer farm in Hunan Province, China. Liver tissues were collected from visibly affected layer chickens for viral isolation in LMH cell cultures. Subsequent phylogenetic analysis was conducted based on DNA sequencing and bioinformatics data to determine the genetic relationships of the isolated virus. Pathogenicity trials were performed on specific-pathogen-free (SPF) chickens. A novel FAdV-8, designated HuN21, with recombination between serotypes FAdV-8a/FAdV-8b, was isolated. Recombination and phylogenetic analyses revealed that this recombinant strain harbored a genomic backbone and fiber gene from FAdV-8a and FAdV-8b, respectively. HuN21’s pathogenicity differed significantly by age groups, showing high pathogenicity (100% mortality, classic IBH signs) in 1-day-old SPF chickens, compared with no mortality despite viral replication in 28-day-old chickens. These data provide robust evidence for recombination between different serotypes of FAdV-8. Notably, the unique genetic and pathogenic characteristics of the HuN21 strain indicate potential as a candidate strain for the development of a bivalent inactivated vaccine or a natural vaccine against FAdV-8a/FAdV-8b. Full article

Aquaculture production of Asian seabass is increasingly threatened by recurrent bacterial diseases, while practical vaccination strategies that provide protection against bacterial challenges involving multiple pathogens during extended grow-out periods remain limited. This study evaluated the immunological and protective effects of a sequential mucosal vaccination strategy in juvenile Asian seabass (Lates calcarifer; 200 fish per treatment, distributed among four replicate tanks of 50 fish) against four major bacterial pathogens: Flavobacterium covae, Vibrio harveyi, Vibrio vulnificus, and Photobacterium damselae. The vaccination regimen consisted of two nanoemulsion-based immersion vaccination events administered 14 days apart, followed by three oral chitosan–alginate hydrogel vaccination courses administered for 7, 5, and 3 consecutive days. Bacterial challenge experiments were conducted at three post-vaccination time points using immersion and intraperitoneal injection models. Growth performance and feed conversion were evaluated using replicate-tank means as the experimental units. Sequential vaccination did not significantly affect final body weight, weight gain, average daily gain, specific growth rate, or feed conversion ratio (p > 0.05). Vaccinated fish showed significantly higher antigen-specific IgM levels in skin mucus, intestinal mucus, and serum across the evaluated challenge conditions. Correspondingly, ighm, ighd, and ight expression was increased in the gills, skin, head kidney, and intestine, indicating enhanced immunoglobulin-associated responses in mucosal and lymphoid tissues. Full-length 16S rRNA gene sequencing showed vaccine-associated changes in gill and intestinal bacterial community composition, including a lower relative representation of several challenge-associated taxa and a higher relative representation of selected commensal-associated taxa. Vaccinated fish showed significantly higher cumulative survival following F. covae immersion, mixed V. harveyi/V. vulnificus/P. damselae immersion, and mixed-pathogen injection challenges (p < 0.05). These findings demonstrate that sequential nanoemulsion immersion priming and oral hydrogel boosting enhanced pathogen-specific humoral responses and increased immunoglobulin-gene expression. The sequential vaccination strategy improved survival following a separate Flavobacterium covae challenge and a combined Vibrio harveyi/Vibrio vulnificus/Photobacterium damselae challenge during the experimental period without adversely affecting growth. This needle-free strategy warrants further evaluation under commercial aquaculture conditions. Full article