Search Results (310)

Background/Objectives: Mastication may influence oral mucosal immunity; however, its association with postprandial salivary secretory immunoglobulin A (s-IgA) dynamics remains unclear. This pilot study examined the association between mean chewing count per bite during rice ball consumption and the postprandial salivary s-IgA response in healthy men. Methods: Thirty-seven healthy adult men were enrolled. Mean chewing count per bite was analyzed continuously and secondarily in exploratory groups defined by the median (<30, n = 18; ≥30 chews/bite, n = 19). Unstimulated whole saliva was collected before, 0–5, 10–15, and 25–30 min after eating. Salivary s-IgA concentration, saliva weight, and s-IgA secretion rate were evaluated as absolute values and baseline ratios. Baseline-adjusted, repeated-measures, and sensitivity analyses were performed. Results: Mean chewing count per bite correlated positively with normalized salivary s-IgA concentration at 10–15 min (ρ = 0.347, p = 0.036) and 25–30 min (ρ = 0.352, p = 0.033), but these associations were attenuated after false discovery rate correction (q = 0.053 for both). Baseline salivary s-IgA was inversely associated with normalized responses. In exploratory group comparisons, normalized salivary s-IgA concentration was higher in the ≥30 chews/bite group at 10–15 and 25–30 min, whereas absolute s-IgA concentration, saliva weight, and s-IgA secretion rate did not differ between groups. Baseline-adjusted associations were not statistically significant. Conclusions: Higher mean chewing count per bite may be associated with greater relative postprandial salivary s-IgA responses in healthy adult men, but these findings are exploratory and should be interpreted cautiously. Full article

Existing vectored immunoprophylaxis (VIP) approaches have primarily focused on IgG, which provides systemic protection but is less specialized in mucosal immunity. In contrast, secretory IgA (sIgA) plays a central role at epithelial surfaces, promoting pathogen neutralization while limiting inflammation. Although monoclonal IgA therapies are effective, their short half-life requires repeated dosing. Thus, VIP strategies enabling sustained sIgA expression at mucosal sites could transform mucosal infection prevention and treatment. This review outlines the key challenges associated with in vivo IgA expression and discusses critical considerations for VIP-mediated IgA delivery at mucosal surfaces, with emphasis on its potential for clinical translation. We provide a detailed overview of platforms for targeted IgA expression, including adeno-associated virus (AAV), adenoviral and lentiviral vectors, and lipid nanoparticle-based systems, alongside relevant routes of administration. Additionally, we examine emerging strategies to enhance the robustness, durability, and localization of IgA expression in vivo. Overall, VIP-enabled IgA expression represents an emerging strategy for enhancing mucosal immunity, with continued advances required to establish its role in the prevention and treatment of mucosal infections. 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

Fucoidan (FUC) exhibits immunomodulatory activity; however, its effects on intestinal mucosal immunity through dendritic cell (DC)-mediated regulation remain unclear. In this study, fucoidan was extracted from Saccharina japonica by hot-water extraction and characterized by chemical composition analysis, gel permeation chromatography (GPC), and Fourier-transform infrared spectroscopy (FT-IR). Bone marrow-derived DCs were used to evaluate the effects of FUC on DC maturation and immune function. An LPS-induced acute enteritis mouse model was used to assess intestinal injury, barrier function, and DC-mediated T/B cell immune responses. Structural analysis confirmed that purified FUC has the sulfated polysaccharide characteristics. FUC promoted DC maturation and enhanced antigen-presenting capacity. In LPS-induced enteritis, FUC reduced IL-1β, IL-6, and TNF-α levels and improved intestinal barrier integrity by restoring the mRNA expression of tight-junction-related genes. Mechanistically, FUC regulated the excessive activation of the TLR4/MyD88/NF-κB pathway, increased TGF-β and IFN-γ expression, modulated Th1/Th17/Treg immune balance, and promoted B cell homing and sIgA secretion. FUC regulates DC-mediated immune responses, repairs intestinal mucosal barrier function, and restores the intestinal immune microenvironment, thereby alleviating LPS-induced intestinal inflammation and maintaining intestinal homeostasis. Full article

Background: The increasing incidence of pediatric food allergy (FA) drives an imperative for mechanistically driven risk stratification beyond descriptive diagnostics. The current systematic review aims to assess the predictive and diagnostic value of early-life non-invasive biomarkers: cord blood IgE (CS-IgE), fecal calprotectin (FC), fecal zonulin (FZ) and secretory IgA (SIgA). Methods: In accordance with the PRISMA guidelines, we performed a systematic literature search on PubMed/MEDLINE and Scopus for English observational studies published in 2009–2025. The titles and abstracts were screened by two independent reviewers and methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Results: A total of 17 studies met the inclusion criteria. This synthesis demonstrates that CS-IgE reflects a systemic atopic predisposition rather than serving as a highly sensitive predictor for isolated FA. Fecal calprotectin was the most consistent marker of inflammatory activity in non-IgE-mediated food allergies, with median values in food allergy ranging from approximately 200 to 410 µg/g and proven useful in dietary monitoring. Fecal zonulin reflects epithelial barrier dysfunction; however, its clinical utility is limited by suboptimal assay specificity. SIgA primarily reflects mucosal immune maturation and tolerance development rather than serving as a direct diagnostic marker. Conclusions: Although CS-IgE, FC, FZ and SIgA exhibit potential in the risk stratification of early FA, their clinical implementation is complicated by methodological heterogeneity and concerns regarding analytical specificity, especially with respect to zonulin assays. We propose an integrated multi-biomarker risk stratification model as a conceptual hypothesis requiring prospective validation in future large-scale studies. Full article

As the predominant antibody isotype at human mucosal surfaces, immunoglobulin A (IgA) exerts critical functions in mucosal defense and systemic immune homeostasis. The two IgA subclasses, IgA1 and IgA2, possess distinct structural and functional features and assemble into dimeric IgA (dIgA) and secretory IgA (sIgA) under physiological conditions. With advances in cryo-electron microscopy, the molecular architecture and assembly of sIgA have been clearly characterized. While IgA protects hosts from pathogenic infection and sustains immune balance, aberrantly altered IgA contributes to the pathogenesis of IgA nephropathy and autoimmune encephalitis. To date, IgA-based therapeutics have displayed promising therapeutic efficacy against respiratory disorders, inflammatory bowel diseases and oral fungal infections. Through standardized retrieval and categorical sorting of the published literature covering IgA structure, physiological functions, disease pathogenic mechanisms and therapeutic research, this review systematically organizes relevant research advances, analyzes the bottlenecks and translational prospects of IgA-targeted therapeutics, and provides objective references to accelerate the clinical translation of IgA antibody agents. 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

Background: Acute lymphoblastic leukaemia (ALL) is the most common paediatric haematological malignancy. Treatment-related immunosuppression compromises mucosal integrity and contributes to oral and dento-maxillary complications, which remain a clinically relevant but insufficiently characterised source of morbidity. Salivary secretory immunoglobulin A (sIgA), the principal antibody of mucosal surfaces, may provide a non-invasive surrogate measure of local immune competence; however, its longitudinal behaviour and relationship with oral morbidity in paediatric ALL remain incompletely characterised. Methods: This prospective, single-centre pilot cohort study included 21 children with newly diagnosed ALL treated at the Fundeni Clinical Institute, Bucharest (March–November 2024). Salivary sIgA was measured at diagnosis (TP1) and after completion of intravenous chemotherapy (TP3). Oral mucositis (OM) was clinically assessed and graded according to WHO criteria at induction (TP2), as well as the predominant WHO grade across the post-induction chemotherapy course. Stomatological evaluation included DMFT/dmft and PUFA/pufa indices, and microbiological screening was performed at predefined time points. Statistical analyses were exploratory and included non-parametric tests and correlation analyses. Results: All patients developed OM at induction (TP2), with 38% experiencing severe forms (WHO grades 3–4). Baseline salivary sIgA (TP1) (n = 15) showed a non-significant weak inverse association with mucositis severity (Spearman ρ = −0.35, p = 0.20); differences across severity groups did not reach statistical significance (Kruskal–Wallis p = 0.43). When grouped, lower median salivary sIgA levels were observed in patients with severe mucositis compared with mild-to-moderate forms (median 91.0 mg/L (IQR 65.0–123.0) vs. 170.5 mg/L (IQR 125.0–231.8); non-significant p = 0.13). A non-significant decline in salivary sIgA was observed from TP1 to TP3 (median 174.5, IQR 127.2–213.8 versus median 111.5, IQR 33.2–142.7; Wilcoxon signed-rank p = 0.084; n = 10 paired measurements). Pre-existing dento-maxillary morbidity was substantial (median DMFT 4.0 (IQR 2.5–5.5), PUFA 3.0 (IQR 1.5–4); dmft 4.0 (IQR 3.0–5.0), pufa 3.0 (IQR 2.0–3.5)), but showed no statistically significant association with either mucositis grade or salivary sIgA levels. No clinically meaningful correlation was observed between salivary and intestinal sIgA levels (Spearman ρ = 0.33 overall; ρ = 0.16 after exclusion of an extreme outlier; p > 0.05 in both analyses), consistent with immunological compartmental independence. Conclusions: In this exploratory pilot cohort, no statistically significant associations were observed between salivary sIgA and oral mucositis severity or dento-maxillary indices. Although trends toward lower baseline salivary sIgA in severe mucositis and declining sIgA during induction therapy were observed, larger adequately powered studies are needed to determine whether these findings represent true biological associations. Full article

Porcine epidemic diarrhea virus (PEDV) remains one of the most critical enteric coronaviruses affecting the global swine industry. PEDV causes severe diarrhea, dehydration, and high mortality in neonatal piglets. Despite the widespread use of commercial vaccines, persistent PEDV outbreaks worldwide indicate that current vaccination strategies provide suboptimal protection. Increasing evidence suggests that the limited effectiveness of current control strategies is primarily attributable to two interrelated factors: continuous antigenic variation among circulating PEDV strains and inadequate induction of maternal mucosal immunity. Unlike systemic viral infections, effective protection against PEDV in neonatal piglets predominantly depends on lactational immunity mediated by the gut–mammary gland–secretory IgA (sIgA) axis. However, most currently available vaccines predominantly induce systemic IgG responses and fail to effectively stimulate intestinal immune imprinting or sustain sIgA secretion in colostrum and milk. In this review, we summarize the mechanisms underlying PEDV evolution and maternal mucosal immunity, with particular emphasis on the gut–mammary gland–sIgA axis. We further discuss the recent advances in and limitations of current vaccine platforms and propose an integrated framework for broadly protective PEDV vaccines based on structural antigen optimization, mucosal-targeted immunization, and sIgA-oriented evaluation systems. This framework may provide new insights into the rational design of more effective maternal vaccines against PEDV and other enteric coronaviruses affecting pigs. Full article

Background: Secondhand exposure to heated tobacco products (HTPs) is increasingly common, but its impact on human milk composition is unclear. We investigated whether secondhand exposure to HTP aerosols affects major human milk components and cotinine concentrations in lactating women. Methods: This observational study included 15 lactating women whose household members used HTPs (secondhand HTP exposure group) and 33 lactating women who did not live with any smokers (non-exposed group). Human milk was analyzed for macronutrients, total solids, energy, lactoferrin, secretory immunoglobulin A (sIgA), calcium, inorganic phosphorus, zinc, and cotinine. Cotinine was measured in all women in the secondhand HTP exposure group and in three women in the non-exposed group. Results: Background characteristics did not differ significantly between groups. No significant differences were observed in lipid, protein, total solids, energy, true protein, lactoferrin, calcium, inorganic phosphorus, or zinc. Carbohydrate concentration differed significantly between the non-exposed and secondhand HTP exposure groups (non-exposed vs. secondhand HTP exposure: 8.20 vs. 8.10 g/dL, p = 0.032), although the absolute difference was small. sIgA tended to be higher in the secondhand HTP exposure group (non-exposed vs. secondhand HTP exposure: 1244 vs. 1706 μg/mL, p = 0.072). Cotinine concentrations did not differ significantly between groups; qualitative cotinine tests were negative in all samples. Conclusions: Secondhand exposure to HTPs was not associated with clear differences in major human milk components or cotinine concentrations. However, the findings should be interpreted cautiously because of the small sample size and limited cotinine assessment. Larger studies with objective exposure assessment and infant follow-up are needed. Full article

This study aimed to determine whether intranasal hinokitiol modulates short-term salivary secretory IgA (SIgA) secretion dynamics and IgA antibody-forming cell (AFC) activity in the submandibular glands of aged mice, a model of age-associated mucosal immune decline. Aged BALB/c mice received intranasal hinokitiol (50 μg) once weekly for 4 weeks. Saliva was collected on days 0, 7, 14, and 21 at baseline, 0.5 h, 1.5 h, 3 h, and 6 h after each administration. SIgA levels were measured using an enzyme-linked immunosorbent assay. On day 21, IgA AFCs were enumerated using an enzyme-linked immunosorbent spot assay, and their viability and proliferative activity were assessed using the MTT assay. Salivary SIgA rose transiently after each dose, peaking at 1.5 h and returning to baseline by 6 h. By day 21, baseline SIgA secretion was significantly higher than at day 0, indicating a cumulative effect. IgA AFCs were unchanged in number, but viability and proliferation increased at 0.5 and 1.5 h, coinciding with SIgA peaks. Flow cytometry revealed significant expansion of B220⁺CD38⁺ memory B-cells; B220⁺CD138⁺ plasma cells were unaffected. Intranasal hinokitiol transiently enhances salivary SIgA secretion in aged mice, likely through short-term modulation of salivary gland immune activity. This non-invasive approach may aid mucosal defense in aging populations. These findings suggest that intranasal HNK may represent a novel non-invasive approach for enhancing mucosal immune function during aging and may provide a basis for future preventive strategies against oral and respiratory infections. Full article

Background/Objectives: In the first months of their life, infants rely on maternal antibodies for immune protection. Breastmilk is a major source of these defenses, supplying secretory IgA, IgG, and IgM that help guard mucosal surfaces against pathogens such as SARS-CoV-2. Most studies on breastmilk immunity in the context of COVID-19 have emphasized circulating monomeric IgA, rather than the multimeric secretory IgA (sIgA) that is active at mucosal barriers. This study assessed in-depth the contribution of breastmilk antibody subtypes to SARS-CoV-2 neutralization capacity and how these profiles differ following maternal COVID-19 infection versus vaccination during pregnancy or postpartum. Methods: In this prospective cohort study, breastmilk samples were collected longitudinally from individuals who had COVID-19 during pregnancy or received COVID-19 mRNA vaccination during pregnancy or postpartum. Serological assays measured IgG, IgM, systemic IgA, and secretory IgA against SARS-CoV-2 spike and nucleocapsid antigens. Results: COVID-19 infection during pregnancy resulted in significantly higher systemic and secretory IgA levels compared to vaccination. Secretory IgA demonstrated a strong correlation with neutralization capacity. Principal component analysis revealed distinct antibody profiles in COVID-19-exposed individuals versus vaccinated cohorts, with significant overlap between pregnancy and postpartum vaccination groups. Conclusions: Although both COVID-19 vaccination and disease elicit sustained COVID-19-related antibodies in breastmilk, COVID-19 infection elicits a broader and more diverse antibody response in breastmilk, specifically with a greater secretory IgA generation. These findings support the value of maternal vaccination to safely confer mucosal immunity to neonates and the need for optimized vaccine formulations for mucosal immunity. Full article

Background/Objectives: The induction of anti-SARS-CoV-2 antibodies by COVID-19 vaccination reduces morbidity and mortality, but immune responses may be compromised in people living with HIV (PLWH). The aims of the current study were to determine whether viral suppression (VS) or immune reconstitution (IR) in PLWH directly affected their ability to produce effective levels of anti-SARS-CoV-2 antibodies in mucosal secretions or blood induced by vaccination. Methods: Anti-SARS-CoV-2 spike IgG, IgA and secretory IgA (SIgA) antibodies and their avidities were measured by ELISA in HIV-negative healthy controls (HC; n = 49) and PLWH (n = 94) using stimulated oral fluid (SOF) and serum. Frequencies of CD4/CD8 T cells and their expression of exhaustion/senescence were determined by flow cytometry. Cytokine levels were measured by cytokine bead arrays. Results: We showed that higher HIV burden negatively impacted the levels of systemic and mucosal anti-SARS-CoV-2 spike IgG antibodies produced. This differential IgG antibody production was unaffected by IR status, antiretroviral therapy duration or T cell exhaustion/senescence. PLWH elicited higher anti-SARS-CoV-2 spike IgA antibodies both in peripheral blood and oral mucosa and highr secretory IgA (SIgA) antibodies in the oral mucosa. PLWH with higher HIV RNA copies elicited lower IgG avidity but the IgA avidity indices remained unaffected. PLWH expressed higher levels of innate immunity cytokines in the oral mucosa, irrespective of the HIV RNA copies. Conclusions: Significantly fewer breakthrough infections in PLWH compared with HC, along with high IgA/SIgA antibodies and increased innate immunity cytokines in the SOF, suggest a potential role for mucosal immunity in the immunopathogenesis of COVID-19. Full article

During the early growth stage, lambs are highly susceptible to pathogenic microbial invasion due to an underdeveloped intestinal structure, unstable microbial colonization, and immature mucosal immune function, leading to diarrhea, growth retardation, and elevated mortality factors that severely constrain the production efficiency and economic viability of the sheep industry. This study aimed to compare the regulatory effects of compound yeast culture (CYC) and yeast polysaccharides (YPs) on intestinal barrier function in Mongolian male lambs and clarify their underlying molecular mechanisms. Eighteen lambs were randomly assigned to three groups (n = 6/group): control group (basal diet), CYC group (40 g/kg), and YP group (3 g/kg). After a 30-day feeding trial, intestinal histomorphology, tight junction proteins, immune signaling pathways, and gut microbiota were analyzed. The results showed that both additives improved intestinal villus morphology, and CYC markedly increased the villus height/crypt depth ratio (p < 0.05). At the mechanical barrier level, CYC upregulated the protein expression of occludin, claudin-1, and ZO-1, whereas YPs increased occludin and ZO-1 expression (p < 0.05). Immunologically, CYC inhibited intestinal inflammation via the TLR4/TRAF6/MyD88/NF-κB pathway, increasing interleukin-10 (IL-10) and secretory immunoglobulin A (sIgA) while decreasing pro-inflammatory cytokines. YPs exerted similar anti-inflammatory effects through the TLR2/MyD88 pathway. Microbial analysis indicated that both additives increased the relative abundance of beneficial bacteria including Eubacterium, Bacillus, and Succinivibrio, while reducing the potential pathogen Mogibacterium. Spearman correlation analysis revealed that Mogibacterium was positively correlated with TNF-α and negatively correlated with occludin expression. In conclusion, CYC and YPs effectively enhance intestinal mechanical, immune, and biological barriers via different TLR-mediated pathways and microbial modulation. Both natural additives have great application potential for improving lamb health, reducing antibiotic dependence, and promoting sustainable green animal husbandry. Full article

The objective of this study is to assess anxiety and chronic stress in fast- and slow-growing broilers when housed with a hut or platform enrichment. We obtained 264 day-old chicks each of Cobb 500, Ross 308, and Ross 708, Redbro-Yield, Redbro M, and Ja57NH strains, and placed them by strain across 72 pens (22 birds/pen) with an A-frame hut or a perforated platform with ramps. Anxiety was assessed via the attention bias test (proportion of birds feeding, vigilance), and chronic stress was assessed through feather corticosterone (fCORT) and secretory immunoglobulin-A (SIgA) concentrations in excreta at 3.7 kg body weight. More Ja57NH broilers began feeding during the test compared to Cobb 500 (p = 0.037) and Ross 708 (p = 0.033) broilers. Redbro M broilers were less vigilant than Ross 308 broilers (p = 0.038). Redbro M broilers had lower fCORT concentrations than Ja57NH broilers (p = 0.019). Redbro M and Ja57NH broilers had lower SIgA concentrations than all fast-growing strains. Enrichment type had no impact on anxiety or chronic stress responses. Both Ja57NH and Redbro M broilers showed improved indicators of affective state (less vigilance, tended to feed more during the test, lower fCORT concentrations) compared to other strains assessed at market weight. SIgA levels seemed strongly impacted by genetics, so SIgA may not be appropriate as an inter-strain comparison of chronic stress. The two fastest-growing broiler strains were genetically predisposed to greater anxiety compared to the two slowest-growing strains, which has implications for their welfare. Full article