Search Results (690)

Background/Objectives: The pandemic caused by SARS-CoV-2 boosted the development of different vaccine models. In parallel, yeasts stand out as a vaccine platform in healthcare biotechnology. Species such as Saccharomyces cerevisiae and Pichia pastoris can express heterologous proteins, which are capable of inducing specific antibodies and can perform as an attractive vaccine vehicle with immunomodulating properties due to their cell wall composition. Furthermore, the yeast surface display system facilitates antigen presentation to immune cells. We developed an oral vaccine based on P. pastoris displaying a synthetic antigen composed of Spike and Nucleocapsid epitopes. Methods: The vaccine was administered to BALB/c mice. Systemic immune response was measured through antibody detection in blood samples, and mucosal immunity was assessed via IgA levels in feces. Histopathological analysis of intestinal and gastric tissues was also conducted. Results: The yeast-based vaccine elicited a humoral immune response, reflected in the production of neutralizing antibodies and elevated levels of IgG2a and IgG2. No structural alterations or pathological changes were observed in gastrointestinal tissues. Conclusions: This study demonstrates the feasibility of using P. pastoris as an oral vaccine delivery system, supporting previous findings with other yeast species such as Saccharomyces cerevisiae, and highlighting its potential in developing effective mucosal vaccines. Full article

The ocular surface microbiome consists of microorganisms that play an important role in maintaining homeostasis and preventing disease from invading pathogens. Commensal microbes on the ocular surface interact with cells and molecules of the ocular surface immune system to promote immune tolerance to the normal flora of the ocular surface and facilitate immune protection against invading pathogenic microbes, which allows for a disease-free ocular surface. Various factors can impact the composition, distribution, and diversity of the ocular surface microbiome, including age, gender, disease state, antibiotic treatment, and contact lens use. In addition, there is no cohesive consensus on the species that make up the ocular surface microbes. There is, however, thorough research present on other similar mucosal membranes, such as the gut and oral mucosa, that share similarities with the ocular mucosa. Exploring the relationship of different mucosae allows us to explore treatment options for common ocular diseases such as dry eye syndrome. This review highlights studies that define the ocular surface microbiome, its diversity and composition, host–immune interactions at the ocular surface, factors that cause dysbiosis of the ocular surface microbiome, the impact of dysbiosis on the ocular surface microbiome, and microbiome-based therapy. Full article

Background/Objectives: Leishmania spp. are protozoan parasites transmitted by female sandflies (Phlebotomus or Lutzomyia). Clinical manifestations depend on species and host immunity. While cutaneous and visceral forms prevail, mucocutaneous involvement—particularly isolated nasal septum leishmaniasis—is rare and frequently misdiagnosed as an inflammatory, infectious, or neoplastic condition. Risk factors associated with mucocutaneous leishmaniasis include systemic or local immunodeficiency, prior renal transplantation, treatment with chronic inhaled steroids, residence in endemic areas or travel to such regions, and previous Leishmania infections. Immunosuppressed patients are at higher risk for atypical presentations and delayed diagnosis, which can result in extensive tissue destruction. Early clinical suspicion, histopathological confirmation, and prompt therapy are essential to prevent permanent mucosal damage. Therefore, a multidisciplinary approach is needed for adequate evaluation and effective treatment. Methods: A 67-year-old man with rheumatoid arthritis on methotrexate reported a two-year history of right-sided nasal obstruction and ulceration that failed to respond to antibiotics. He did not present systemic symptoms. Results: Facial CT revealed a septal deviation; the patient underwent septoplasty, and biopsy confirmed Leishmania amastigotes. Serology (rK39 immunochromatographic test) was positive. He was treated with liposomal amphotericin B at 4 mg/kg/day for five days, followed by miltefosine at 100 mg/day orally for 14 days. At an eight-week follow-up, the nasal mucosa was fully healed, obstruction was resolved, and there was no evidence of recurrence. Conclusions: Although nasal septum leishmaniasis is uncommon, it should be considered in the differential diagnosis of chronic nasal lesions, especially in immunocompromised patients or those from endemic regions. Definitive diagnosis requires biopsy with histological or molecular confirmation. Combined liposomal amphotericin B and miltefosine therapy yields high cure rates and prevents mucosal destruction. Early recognition is critical to avoid diagnostic delays and long-term sequelae. Full article

Background: African swine fever (ASF) is a highly contagious and often deadly disease that poses a major threat to swine production worldwide. The lack of a commercially available vaccine underscores the critical need for innovative immunization strategies to combat ASF. Methods: Six ASFV antigenic proteins (K78R, A104R, E120R, E183L, D117L, and H171R) were fused with the Lactiplantibacillus plantarum WCFS1 surface anchor LP3065 (LPxTG motif) to generate recombinant Lactiplantibacillus plantarum NC8 (rNC8) strains. The surface expression was confirmed using immunofluorescence and Western blotting assays. Additionally, the dendritic cell-targeting peptides (DCpep) were co-expressed with each antigen protein. Mice were immunized at a dosage of 10⁹ colony-forming units (CFU) per strain per mouse via intragastric (I.G.), intranasal (I.N.), and intravenous (I.V.) routes. The bacterial mixture was heat-inactivated by boiling for 15 min to destroy viable cells while preserving antigenic structures. I.V. administration caused no hypersensitivity, confirming the method’s safety and effectiveness. Results: Following I.G. administration, rNC8-E120R, rNC8-E183L, rNC8-K78R, and rNC8-A104R induced significant levels of secretory immunoglobulin A (sIgA) in fecal samples, whereas rNC8-H171R and rNC8-D117L failed to induce a comparable response. Meanwhile, rNC8-D117L, rNC8-K78R, and rNC8-A104R also elicited significant levels of sIgA in bronchoalveolar lavage fluid (BALF). Following I.N. immunization, rNC8-E120R, rNC8-K78R, and rNC8-A104R significantly increased sIgA levels in both fecal and BALF immunization. In contrast, I.V. immunization with heat-inactivated rNC8-K78R and rNC8-A104R induced robust serum IgG titers, whereas the remaining antigens elicited minimal or insignificant responses. Flow cytometry analysis revealed expanded CD3⁺CD4⁺ T cells in mice immunized via the I.N. and I.G. and CD3⁺CD4⁺ T cells only in those immunized via the I.N. route. Th1 responses were also significant in the sera of mice immunized via the I.G. and I.N. routes. Conclusions: The rNC8 multiple-antigen cocktail elicited strong systemic and mucosal immune responses, providing a solid foundation for the development of a probiotic-based vaccine against ASF. Full article

Background: Haemophilus influenzae (Hi), a Gram-negative bacterium, is divided into two broad categories: encapsulated and non-capsulated isolates, also called non-typeable Hi isolates (NTHi). NTHi has become prevalent since the introduction of the vaccine against Hi of serotype b. Hi can cause local infections on respiratory mucosal surfaces and urogenital infections, which can lead to septic abortion in pregnant women. It can also cause invasive infections such as meningitis and septicemia. Moreover, NTHi isolates are becoming increasingly resistant to antibiotics. Vaccines targeting NTHi are not yet available. As these NTHi isolates are not encapsulated, vaccines should target proteins at the bacterial surface. However, vaccine development is hindered by the high variability of these proteins. We aimed to identify conserved outer membrane proteins (OMPs) for vaccines against NTHi. Methods: We analyzed core-genome multilocus sequence typing (cgMLST) of 1144 genomes of Hi collected between 2017 and 2022 and, of these, identified 514 conserved genes that encoded OMPs. We focused on two specific OMPs: Haem1295, encoding the protein P5 (P5), and Haem1040, encoding the protein 26 (P26). P5 is known to bind human complement regulatory protein factor H (FH), while both P5 and P26 are involved in enhancing immune responses. The genes encoding these proteins were cloned, overexpressed, purified, and tested in both active and passive protection models using systemic infection in mice. Results: P5 and P26 were found to be immunogenic during human infections. Vaccination with these proteins conferred protection against both homologous and heterologous NTHi isolates in mice, suggesting broad cross-protection. Conclusions: P5 and P26 are promising vaccine candidates showing cross-protection against NTHi and offering the additional benefit of targeting bacterial virulence factors, enhancing vaccine efficacy against NTHi isolates. Full article

Retinoic acid (RA) plays a key role in mucosal immune regulation and tolerance, with implications for inflammatory bowel disease (IBD). However, its effects have not been extensively studied in humanized in vitro models that recapitulate epithelial–immune interactions. We established a 3D in vitro small intestinal model composed of three epithelial cell types, naïve CD4⁺ T cells, and monocyte/dendritic cell (M/DC) precursors derived from CD34⁺ umbilical cord blood hematopoietic stem/progenitor cells. The epithelial microenvironment strongly suppressed monocyte/DC differentiation and T cell activation, indicating a regulatory role of epithelial-derived signals. Retinoic acid (RA) priming of M/DC precursors induced CD103⁺CD11b⁺Sirp1α⁻ regulatory DCs and promoted a shift from naive to memory-type T cells. Upon addition of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β), the model mimicked an inflamed intestinal state, resulting in CD14⁺CD16⁺ inflammatory monocytes and increased T cell activation (CD25⁺CD69⁺). RA-primed DCs modestly counterbalanced T cell activation and IBD-like responses, even under inflammatory conditions. Flow cytometry and clustering analysis revealed distinct immune cell phenotypes depending on RA exposure and cytokine context. This model provides a reproducible and physiologically relevant human system to study RA-mediated immune programming in the intestinal mucosa and may support the development of novel therapeutic strategies for IBD and related inflammatory conditions. Statistical differences were evaluated using ANOVA with Tukey’s post-hoc test (n = 4; p < 0.05). Full article

Burning mouth syndrome (BMS) and oral lichen planus (OLP) are two chronic oral diseases/disorders that continue to pose a challenge for conventional diagnosis and treatment. Both diseases do not occur in isolation but rather appear to reflect a broader interplay of psychological, neurological, endocrine, and immunological factors, i.e., complex disorders in interconnected biological and psychological systems. In BMS, patients often suffer from persistent burning sensations without visible lesions, which may be related to altered pain processing, emotional stress, and dysregulation in the brain regions responsible for interoception and perception. Although OLP is primarily characterised by immune-mediated mucosal damage, it often has significant psychological comorbidity, particularly in the erosive form. Common features such as cortisol imbalance, disturbed cytokine patterns, and high levels of anxiety and depression suggest that these conditions may be due to overlapping systemic disorders. It is no longer sufficient to focus only on the visible lesions or symptom relief. Understanding these diseases/disorders through a more comprehensive psychoneuroendocrine immune system (PNEI) opens up new opportunities for early intervention, improved diagnostics, and more personalised therapeutic strategies that go beyond treating symptoms. Ultimately, these diseases/disorders require a more integrated and patient-centred approach, where understanding the whole system is as important as treating its individual parts. Full article

Veterinary vaccines are essential tools for controlling infectious and zoonotic diseases, safeguarding animal welfare, and ensuring global food security. However, conventional vaccines are hindered by cold-chain dependence, thermal instability, and logistical challenges, particularly in low- and middle-income countries (LMICs). This review explores next-generation veterinary vaccines, emphasizing innovations in thermostability and delivery platforms to overcome these barriers. Recent advances in vaccine drying technologies, such as lyophilization and spray drying, have improved antigen stability and storage resilience, facilitating effective immunization in remote settings. Additionally, novel delivery systems, including nanoparticle-based formulations, microneedles, and mucosal routes (intranasal, aerosol, and oral), enhance vaccine efficacy, targeting immune responses at mucosal surfaces while minimizing invasiveness and cost. These approaches reduce reliance on cold-chain logistics, improve vaccine uptake, and enable large-scale deployment in field conditions. The integration of thermostable formulations with innovative delivery technologies offers scalable solutions to immunize livestock and aquatic species against major pathogens. Moreover, these strategies contribute significantly to One Health objectives by mitigating zoonotic spillovers, reducing antibiotic reliance, and supporting sustainable development through improved animal productivity. The emerging role of artificial intelligence (AI) in vaccine design—facilitating epitope prediction, formulation optimization, and rapid diagnostics—further accelerates vaccine innovation, particularly in resource-constrained environments. Collectively, the convergence of thermostability, advanced delivery systems, and AI-driven tools represents a transformative shift in veterinary vaccinology, with profound implications for public health, food systems, and global pandemic preparedness. Full article

An alternative fish feed (ALT) replacing 50% of the fishmeal with poultry byproduct meal and insect meal and total fish oil with microalgae, poultry, and salmon byproducts oils was tested for 300 days on 900 gilthead seabream (Sparus aurata) with an initial body weight of 17.1 ± 1.8 g (mean ± SD) of unselected (REF) and selected (HG) genotypes. Using in situ, histochemistry, and immunohistochemistry techniques, we assessed the immune response by characterizing IgT and IgM immunoglobulins, CD3ε⁺ T lymphocytes, and eosinophilic granular cells (EGCs) along the digestive system. IgT mRNA⁺ cells were concentrated in the second part of the digestive tract, while IgM⁺ predominated in the first and occasionally showed intraepithelial localization. CD3ε⁺ and EGCs were most prominent in the midgut. The diet affected IgT and IgM mRNA⁺ cells mainly in the initial part of the digestive tract. For CD3ε⁺, the diet only affected the initial and final parts, while the ALT diet increased EGC abundance across the middle compartments. Genetic selection had minimal effect on IgT⁺ and CD3ε⁺ cells, affecting only the first compartments. The REF group showed higher IgM⁺ cell abundance in specific regions, while EGCs differed between genotypes, favoring anterior accumulation in HG and ileocecal abundance in the REF group. Full article

Critical illness profoundly disrupts the gut microbiota leading to a state of dysbiosis characterized by reduced microbial diversity and overrepresentation of pathogenic taxa such as Enterobacteriaceae and Proteobacteria. This dysbiotic shift compromises gut barrier integrity and modulates immune responses, contributing to systemic inflammation and increasing susceptibility to nosocomial infections and multi-organ dysfunction. Nutritional strategies in the ICU significantly influence the composition and function of the gut microbiota. Enteral nutrition supports the maintenance of microbial diversity and gut mucosal health, whereas parenteral nutrition is associated with mucosal atrophy and further microbial imbalance. Emerging interventions, including the administration of probiotics, prebiotics, synbiotics, and fermented products like kefir, show promise in restoring microbial equilibrium and improving patient outcomes. This review presents current evidence on the alterations of the gut microbiota in critically ill patients, explores the systemic consequences of dysbiosis, and evaluates the impact of nutritional and microbiota-targeted therapies in improving patient outcomes. Full article

Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8⁺ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article

IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article

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

Background/Objectives: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. Methods: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from Chlamydia trachomatis major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. Results: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. Conclusions: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime–boost regimen and route of administration. Full article

Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review and meta-analysis assessed their immunogenicity, safety, and protective efficacy. Methods: The study design was a systematic review and meta-analysis, searching PubMed and Cochrane databases up to 30 May 2025. Inclusion criteria followed the PICOS framework, focusing on mucosal vaccines for COVID-19, influenza, RSV, pertussis, and tuberculosis. Results: A total of 65 studies with 229,614 participants were included in the final analysis. Mucosal COVID-19 vaccines elicited higher neutralizing antibodies compared to intramuscular vaccines (SMD = 2.48, 95% CI: 2.17–2.78 for wild-type; SMD = 1.95, 95% CI: 1.32–2.58 for Omicron), with varying efficacy by route (inhaled VE = 47%, 95% CI: 22–74%; intranasal vaccine VE = 17%, 95% CI: 0–31%). Mucosal influenza vaccines protected children well (VE = 62%, 95% CI: 30–46%, I² = 17.1%), but seroconversion rates were lower than those of intramuscular vaccines. RSV and pertussis vaccines had high seroconversion rates (73% and 52%, respectively). Tuberculosis vaccines were reviewed systemically, exhibiting robust cellular immunogenicity. Safety was comparable to intramuscular vaccines or placebo, with no publication bias detected. Conclusions: Current evidence suggests mucosal vaccines are immunogenic, safe, and protective, particularly for respiratory diseases. This review provides insights for future research and vaccination strategies, though limitations include varying efficacy by route and study heterogeneity. Full article