Search Results (735)

Bovine neonatal diarrhea (BND) is a leading cause of morbidity and mortality in pre-weaned calves. Commercial maternal vaccines targeting bovine rotavirus (BRV), bovine coronavirus (BCoV), and enterotoxigenic Escherichia coli (ETEC) have been available for decades, yet field outbreaks continue in vaccinated herds. This review examined peer-reviewed literature published between January 2019 and March 2026, identified through a structured PubMed search supplemented by reference-list screening. For BRV, a field strain sharing its VP7 genotype with a vaccine component was not neutralized by vaccine-induced antiserum, indicating that genotype concordance does not predict serologic coverage. For BCoV, hemagglutinin-esterase variation and regional lineage divergence indicate surface-protein evolution, although data linking these changes to reduced efficacy are not available. For ETEC, adhesin diversity and antimicrobial resistance affect both vaccination strategy and case management. Maternal vaccination retains biological value, but field performance is constrained by colostral variability, incomplete passive transfer, and product-to-product immunogenic differences. For all three pathogens, antigenic divergence from vaccine strains is located at individual epitopes, receptor-binding domains, or adhesins rather than at the level of whole-pathogen identity. Subunit and multi-epitope antigen designs, for which proof-of-concept constructs have been reported, operate at this level, and their selection requires characterization of candidate antigens for efficacy, diversity, polymorphism, and cross-protective breadth. Such antigen improvements address the pathogen-side gap but not the passive-transfer and mucosal constraints. Functional surveillance to guide antigen updating, field trials that measure passive-transfer efficiency, and adjunctive strategies are identified as priorities for BND control. Full article

Tenacibaculosis, caused by Tenacibaculum maritimum, remains a major bacterial disease affecting marine aquaculture, particularly European seabass farming. This study evaluated the immune response and protective efficacy of a formalin-inactivated T. maritimum vaccine administered by immersion or intraperitoneal (i.p.) injection in European seabass (Dicentrarchus labrax). Each vaccination strategy was evaluated using its corresponding experimental challenge model 36 days post-vaccination. Vaccine performance was assessed by relative percentage of survival (RPS), expression of selected immune-related genes (IL-1β, IL-10, IgT), and specific serum IgM production. Intraperitoneal vaccination followed by i.p challenge provided significant protection, with 87% survival and an RPS of 67, accompanied by elevated serum IgM levels and pronounced systemic immune activation. Immersion-vaccinated fish also showed complete survival; however, the unexpectedly low mortality in the corresponding mock-vaccinated controls limited the discriminatory capacity of the immersion challenge model and prevented a robust assessment of vaccine efficacy according to the defined criteria. Gene expression analysis revealed distinct immune profiles, with immersion vaccination inducing an early but transient response, whereas i.p. vaccination elicited stronger and more sustained systemic activation, particularly within innate and humoral immune pathways. Principal component analysis further demonstrated clear clustering of immune responses according to vaccination route. These findings demonstrate the potential of an autogenous vaccine to protect European seabass against tenacibaculosis and highlight the importance of considering both vaccination route and the challenge model when interpreting vaccine efficacy. Further studies should optimise immersion vaccination protocols and investigate local mucosal immune responses to support the development of effective vaccination strategies for juvenile European seabass. Full article

Influenza remains a persistent global health threat, accounting for an estimated one billion infections and 350,000–600,000 deaths worldwide annually. Beyond substantial mortality and morbidity, influenza imposes major socio-economic costs through healthcare utilisation and productivity losses, amounting to tens of billions of dollars each year. Current seasonal vaccination strategies are constrained by rapid antigenic evolution, which necessitates frequent vaccine reformulation and contributes to suboptimal vaccine efficacy across seasons. These drawbacks highlight the need for a universal influenza vaccine (UIV) that protects against all seasonal and potential pandemic influenza strains via a single dose. This review evaluates the feasibility of a UIV as an alternative to a seasonal influenza vaccine (SIV) by consolidating evidence from current UIV candidates in preclinical and clinical development across a diverse range of platforms and target epitopes. Preclinical studies and clinical trials have demonstrated the safety and tolerability of multiple candidates, as well as their ability to elicit broadly cross-reactive immune responses. However, several challenges remain regarding the long-term efficacy of these vaccines. In particular, pre-existing host immunity can shape subsequent vaccine responses, with immune imprinting introducing biases toward previously encountered influenza strains, potentially reducing vaccine effectiveness. In addition, the genetic plasticity of influenza viruses, driven by ongoing mutations and genetic reassortment, raises concerns about the ability of a single vaccine formulation to maintain broad and durable protection. Overall, several UIV candidates have shown promising early results. Although ecological and immunological barriers remain, a UIV could become a viable alternative to, or eventual replacement, for SIVs. Full article

Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A/PR/8/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFNγ+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies. Full article

The pet food industry is undergoing a significant transformation, driven by the growing trend of companion animal humanization and increasing concerns over the environmental sustainability of conventional protein and lipid sources. Consumers now seek diets that not only meet basic nutritional requirements but also offer preventive health benefits. Microalgae, including Arthrospira (Spirulina, a kind of cyanobacterium), Chlorella, Schizochytrium, and Euglena gracilis, have emerged as versatile biological platforms capable of addressing both functional and sustainability challenges. These microorganisms produce high-quality proteins, omega-3 long-chain polyunsaturated fatty acids (particularly docosahexaenoic acid, DHA), natural pigments, and immunomodulatory polysaccharides. This review synthesizes findings from peer-reviewed studies on the application of microalgae in pet nutrition, covering dogs, cats, and aquatic companion animals. We examine how algal ingredients influence gut microbiota, for instance, by enriching beneficial genera such as Turicibacter and Peptococcus, enhance vaccine responses and mucosal immunity, support cognitive function in aging pets, and contribute to weight management. Particular attention is given to Euglena gracilis and its paramylon (β-1,3-glucan), a pathogen-associated molecular pattern that engages the Dectin-1 pathway to train innate immunity and has demonstrated antiviral activity through host defense mechanisms. The review also surveys the patent landscape, highlighting trends in palatability enhancement, hypoallergenic formulations, and novel delivery formats. Key challenges remain, including ingredient standardization, safety validation, palatability optimization, and consumer acceptance. We outline a translational roadmap that prioritizes well-designed clinical trials in target species and processing methods that preserve bioactivity. Collectively, the evidence positions microalgae, and Euglena gracilis in particular, as promising candidates for next-generation functional pet foods that deliver health benefits alongside ecological sustainability. Full article

Bacterial extracellular vesicles (BEVs) are nano-sized lipid bilayer particles secreted by bacteria, capable of carrying various proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs). The biosynthetic pathway of BEVs determines their load components, physicochemical properties, and different biological activities. Increasing evidence indicates that BEVs play an important role in mediating host immune responses and the dynamic regulation of bacterial biofilms. Additionally, BEVs may serve as a molecular bridge between the two. BEVs derived from pathogens can trigger pro-inflammatory cascades, assist bacteria in immune evasion, and further accelerate the maturation of biofilms, forming a vicious cycle of persistent infection and inflammatory damage. In contrast, BEVs derived from probiotics can maintain host immune homeostasis and exert direct anti-biofilm and synergistic antibacterial effects, thereby breaking the pathological cycle. However, significant methodological research bottlenecks have greatly hindered the comparability and clinical translation of BEVs research. This article systematically summarizes the classification of BEVs and their biosynthetic mechanisms, compares the differential effects of BEVs from pathogenic bacteria and probiotic bacteria on immunity, clarifies the dual regulatory role of BEVs throughout the life cycle of biofilms, and highlights the bridging function of BEVs in the immune–biofilm interaction. Additionally, this article also discusses the current development of BEVs in clinical translation applications, such as vaccine development, antibiotic delivery, and mucosal inflammation intervention, and outlines the key industrial and clinical challenges faced in the future development of BEVs-based therapeutic approaches. 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

Mycobacterium bovis Bacille Calmette–Guérin (BCG), the only licensed vaccine against tuberculosis, provides inconsistent protection against pulmonary tuberculosis, reflecting an incomplete understanding of how vaccine-induced immunity is organized within tissues. Emerging evidence indicates that the route of vaccination is not merely a technical variable but a critical determinant of immune programming. Whereas parenteral BCG primarily elicits systemic immune responses, mucosal delivery reprograms immunity at the respiratory interface by promoting localized trained innate immunity, tissue-resident memory T (T_RM) cells, and early containment of infection. In this review, we propose an integrated framework of “immune layering,” in which protection emerges through the coordinated interactions of epithelial regulation, trained innate immunity, tissue-resident adaptive memory, regulatory homeostasis, and systemic immune support across spatial and temporal scales. Within this framework, trained innate immunity serves as an initial conditioning layer that shapes subsequent adaptive differentiation, whereas epithelial- and microbiota-associated regulatory networks establish the tissue context in which immune responses are initiated, organized, and maintained. Importantly, effective mucosal immunity depends on a dynamically regulated equilibrium rather than maximal immune activation. The dissociation between enhanced early pulmonary immune responses and limited long-term protection underscores the influence of tissue-specific regulatory constraints and environmental context on vaccine efficacy. This framework redefines correlates of protection by identifying the vaccination route and tissue-level immune organization as fundamental determinants of protective immunity, thereby providing a conceptual foundation for the rational development of next-generation mucosal tuberculosis vaccines. Full article

Inhalable ribonucleic acid (RNA) nanomedicines are emerging as versatile therapeutics for respiratory diseases and pulmonary metastases, enabling localized delivery of messenger RNA (mRNA), small interfering RNA (siRNA), antisense oligonucleotides, microRNA (miRNA) mimics, self-amplifying RNA, and genome-editing systems. This review synthesizes the available evidence and argues that the field has moved beyond asking whether RNA can reach the lungs. The more consequential translational question is whether RNA cargo, nanocarrier, excipients, manufacturing process, inhalation device, and pulmonary target cell can be integrated into a reproducible therapeutic product. Current research demonstrates progress in disease-corrective mRNA expression, silencing of inflammatory and fibrotic pathways, mucosal vaccination, antiviral therapy, and localized cancer treatment, alongside advances in ionizable lipid nanoparticles, lipid–polymer hybrids, chitosan and polyethyleneimine (PEI) polyplexes, dendrimers, peptide carriers, biomimetic systems, and dry-powder formulations. Translational maturity, however, remains uneven. Many studies demonstrate carrier feasibility, reporter expression, or preclinical activity, whereas fewer establish device-compatible aerosolization, preservation of RNA integrity during processing, traversal of pulmonary barriers, target-cell engagement, repeat-dose tolerability, and clinically meaningful benefit. Development should therefore be target-defined, analytically gated, device-specific, and outcome-centered. Inhalable RNA nanomedicines are best understood as integrated pulmonary products whose success depends on preserving RNA function throughout manufacturing, aerosolization, post-deposition barrier navigation, intracellular delivery, and disease-relevant pharmacodynamic activity. Full article

Pharyngeal infection with high-risk human papillomavirus (HPV), particularly HPV16, is biologically distinct from cervical infection because it occurs within the specialized lymphoepithelial environment of Waldeyer’s ring. This review evaluates nanoparticle materials for the prevention, detection, and treatment of pharyngeal HPV, with an emphasis on structure–property–function relationships, mucosal performance, and translational feasibility. Lipid nanoparticle platforms, polymeric nanoparticle platforms, inorganic systems, and hybrid platforms are compared with respect to composition, particle size distribution, surface charge, colloidal stability, biodegradability, payload compatibility, release behavior, and manufacturing complexity. Evidence suggests that lipid and polymeric systems are the most credible near-future candidates for mucosal vaccination and localized nucleic acid delivery because they offer the best balance between controllable fabrication, analytical tractability, and biologically plausible performance in mucus-exposed tissue. By contrast, the development of inorganic theranostics and CRISPR-enabled platforms remains at an earlier stage because repeated mucosal dosing, retention in lymphoid tissue, and combined product regulation impose substantial burdens. A translational roadmap is proposed in which material selection is guided by clinically relevant quality attributes, standardized saliva- and mucus-relevant assays, human tonsil organoid testing, and early attention to manufacturability, safety, and regulatory strategy. The field is promising, but direct pharyngeal HPV data remain limited; accordingly, there is an urgent need for comparative studies that connect nanoparticle architecture to measurable outcomes such as tonsillar deposition, epithelial uptake, immune activation, and local tolerability. Full article

Porcine epidemic diarrhea virus (PEDV) is a major enteric coronavirus that causes severe economic losses to the global swine industry. Current vaccines suffer from weak immunogenicity, insufficient mucosal immunity, and a short duration of protection. Nanoparticle delivery systems have emerged as a promising strategy for next-generation vaccine development. In the present study, we constructed an S1-Ferritin nanoparticle vaccine using the SpyTag-SpyCatcher modular conjugation system. The morphology, particle size, and uniformity of the nanoparticle vaccine were systematically characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). After two immunizations, the S-Ferritin nanoparticle vaccine elicited potent humoral and cellular immune responses in both mice and piglets. In piglets, at 2 weeks post booster vaccination, PEDV-specific serum IgG endpoint titers peaked at 1:2560, virus-neutralizing antibody titers reached 1:256 against the JS-2/2015 strain, and serum IFN-γ levels reached 274 pg/mL. All these immunological indicators were significantly higher than those observed in the PEDV-inactivated whole-virus vaccine group. Furthermore, challenge tests showed that the S1-Ferritin nanoparticle vaccine provided complete protection against PEDV infection and significantly reduced the severity of diarrhea and intestinal damage in piglets after challenge. These findings suggest that the S1-Ferritin nanoparticle vaccine constitutes a promising candidate against PEDV infection, though our study is only a preliminary step and subsequent field trials in pigs are still required. Full article

A field trial was conducted on a single commercial swine farm to compare the integrated control efficacy of an inactivated vaccine and a live attenuated vaccine against mycoplasmal pneumonia of swine (MPS). Mhp exposure in the herd was confirmed by qPCR prior to trial initiation. Initially, 30 five-day-old piglets were randomly assigned to three groups (10 piglets per group): non-immunized control, inactivated vaccine, and live attenuated vaccine, for clinical safety evaluation. Based on this, another 900 five-day-old piglets, confirmed Mhp-negative by antigen detection, were randomly allocated to three separate rearing zones (300 piglets per zone), with each zone randomly assigned to one of the three treatment groups. Parameters assessed included mucosal (sIgA) and serum (IgG) antibody levels, pulmonary inflammatory cytokine (e.g., IL-1β, IL-6, TNF-α) expression, lung lesion scores, and histopathological changes, with all evaluations performed by technicians blinded to group allocation. Growth performance and economic indicators were also recorded. Both vaccines exhibited favorable safety profiles. The live attenuated vaccine significantly enhanced nasal sIgA and serum IgG levels (p ≤ 0.01), whereas the inactivated vaccine only significantly elevated serum IgG (p ≤ 0.01) but had no significant effect on sIgA (p ≥ 0.05). The live attenuated vaccine group showed the lowest lung lesion scores, as well as the mildest pulmonary inflammation and pathological damage. Meanwhile, swine in this group achieved higher average daily gain, lower mortality, and lower feed conversion ratio, with a 3-day shorter rearing period than the non-immunized group and an 11.27 CNY reduction in combined vaccination and medication cost per swine compared with the inactivated vaccine group. In conclusion, under the conditions of this single-farm trial, the live attenuated vaccine demonstrated superior efficacy in integrated MPS control and production performance improvement. Full article

(1) Background: Vaccination is crucial for Ctenopharyngodon idella, yet the impact of delivery methods on welfare and immunity requires investigation. (2) Methods: This study compared manual (HI-V) and automated (AI-V) injections of inactivated Aeromonas hydrophila vaccine. (3) Results: Both methods induced protective immunity, with AI-V achieving a slightly higher Relative Percent Survival (41.67%) than HI-V (37.84%). AI-V promoted stable erythropoiesis and robust systemic/mucosal IgM responses with elevated HSP70 and IL-6. Conversely, HI-V triggered sharp transient stress and upregulated Gadd45γ, indicating greater genotoxic stress. (4) Conclusions: Automated injection offers comparable immune protection with reduced physiological stress and improved homeostasis, supporting its use for welfare-conscious aquaculture. Full article

Feline panleukopenia is a highly contagious and often fatal disease in cats caused by the feline panleukopenia virus (FPV), a member of the Parvoviridae family. Despite the widespread use of vaccination, FPV remains a significant threat to both domestic and wild felid populations worldwide, particularly in young or unvaccinated animals. Effective vaccination strategies are therefore essential for controlling the disease and reducing mortality. Current vaccines, including modified live and inactivated vaccines, have demonstrated substantial efficacy in inducing protective immunity; however, several challenges remain, such as maternal antibody interference, vaccine failure, and safety concerns in certain animal populations. Recent advances in vaccine technology have spurred the development of next-generation FPV vaccines, including recombinant vectors, DNA vaccines, virus-like particle (VLP) vaccines, and novel delivery platforms. Among these, probiotic-based vaccine vectors have garnered growing interest due to their favorable safety profiles, mucosal immunogenicity, and suitability for oral administration. These systems may provide innovative approaches for inducing both systemic and mucosal immune responses against FPV. This review summarizes the current understanding of the immunological mechanisms underlying protection against FPV infection and discusses the progress made in FPV vaccine development. Furthermore, it highlights the major challenges associated with current vaccination strategies and explores emerging vaccine platforms, including probiotic vector-based vaccines, as promising tools for future disease control. Improved vaccine design and optimized immunization strategies will be crucial for enhancing the prevention of feline panleukopenia in the future. Full article

Respiratory mucosal vaccination can induce robust humoral and cellular immune responses, as well as effective mucosal immunity at the primary site of pathogen entry, and has been shown to provide superior protection against respiratory viral infections compared with traditional approaches. Among current vaccine technologies, mRNA vaccines offer unique advantages, including rapid development, flexible antigen design, and potent immunogenicity. However, efficient mucosal delivery of mRNA remains challenging due to biological barriers within the respiratory tract, including mucus clearance, limited cellular uptake, and instability during aerosolization. Furthermore, mRNA formulations intended for respiratory mucosal delivery require more stringent safety and tolerability profiles. Recent advances in nanoparticle engineering have accelerated the development of mRNA delivery systems optimized for respiratory mucosal immunization. This review aims to evaluate how nanoparticle engineering strategies can overcome respiratory mucosal barriers and improve the safety, stability, delivery efficiency, extrahepatic expression, and immunogenicity of mRNA vaccines and therapeutics. We summarize recent progress in engineered mRNA nanoparticle platforms for respiratory mucosal immunity, encompassing modified lipid nanoparticles (LNPs), polymer-based mRNA nanoparticles, and hybrid nanoparticle systems, including lipid-inorganic, polymeric hybrid, and lipid-extracellular vesicle (EV) nanoparticles. We further discuss optimization strategies for mucosal mRNA delivery, including the incorporation of appropriate adjuvants, the development of polyethylene glycol (PEG) alternatives, and advanced delivery approaches. Finally, we highlight current challenges and future directions for the rational design of next-generation mRNA nanoparticle platforms that can induce durable and broadly protective mucosal immunity against respiratory viral infections. Full article