Search Results (4,028)

Human anti-αGal antibodies (Abs), known for their marked polyreactivity, have been detected bound to the gray matter of the brains of Alzheimer’s disease (AD) patients, although their targets were unclear. Since αGal is a strictly xenogenic antigen absent in humans, this observation raised questions regarding the nature of the structures recognized by these antibodies. In this study, we investigated their potential interaction with gangliosides—glycan structures that are highly abundant in the central nervous system. Using a competitive inhibition ELISA, serum profiles of anti-αGal Abs isotypes and their indirect cross-reactivity with selected soluble gangliosides were analyzed in AD patients and healthy subjects (HSs). AD patients showed reduced levels of anti-αGal IgG and IgM, but increased IgA compared to HSs. Notably, pre-incubation with GM1, GM2, or GD1b did not reduce αGal–HSA binding in HS sera. In contrast, in AD sera, pre-incubation with GD1b reduced residual αGal–HSA binding for all antibody isotypes; additionally, GM1 inhibited IgM binding, and GM2 inhibited IgA binding. These results should therefore be interpreted as competitive inhibition patterns consistent with ganglioside-associated cross-reactivity rather than as direct evidence of antibody binding to immobilized gangliosides. Overall, the findings provide preliminary evidence that, in AD sera, a fraction of αGal–HSA-reactive antibodies can be competitively inhibited by selected gangliosides. This observation supports the presence of an altered humoral anti-carbohydrate signature in AD and identifies neuronal gangliosides as plausible candidate autologous targets that may help explain the previously reported binding of anti-αGal Abs to gray matter. However, given the indirect nature of the assay, these data should be considered hypothesis-generating and require confirmation by direct binding approaches. Full article

Background: Despite the circulation of evolutionarily related cold-causing coronaviruses (CCCs) in the pre-COVID era, most individuals lacked pre-existing serum IgG and/or class-switched memory B cell (B_mem) reactivity for the SARS-CoV-2 Spike (S) glycoprotein expressed by the ancestral Wuhan-Hu-1 (WH1) strain. Subsequent priming of the immune system through natural infection or prophylactic COVID-19 mRNA vaccination successfully generated robust B_mem responses against the WH1-S antigen, along with eliciting cross-reactivity for the future Omicron (BA.1) variant responsible for breakthrough infections (BTIs). However, to what extent immunological imprinting of B_mem towards the WH1-S antigen detrimentally constrains the elicitation of variant-specific antibody responses following subsequent booster vaccinations or BTIs—a phenomena referred to as “original antigenic sin”—remains an unresolved and open question. Methods: Using ImmunoSpot^®, we evaluated peripheral blood mononuclear cells (PBMCs) from defined human cohorts for IgG⁺ ASC reactivity against Spike proteins representing CCCs and SARS-CoV-2. Additionally, we developed a novel dual-label inverted FluoroSpot assay to distinguish between strain-specific and cross-reactive IgG⁺ ASCs recognizing epitopes in the receptor binding domain (RBD) of SARS-CoV-2 Omicron variants. Results: Our data demonstrate a lack of appreciable back-boosting of IgG⁺ B_mem recognizing structurally conserved epitopes shared between CCCs and SARS-CoV-2. Moreover, we found evidence for immunological imprinting and the preferential expansion of B_mem recognizing cross-reactive epitopes in the RBD following BTI. Nevertheless, Omicron strain-specific B_mem were detected in PBMC donors collected in 2025. Conclusions: Our novel inverted dual-label FluoroSpot methodology evidenced preferential expansion of cross-reactive B_mem following breakthrough SARS-CoV-2 infection and supports the influence of original antigenic sin shaping the recall response. Moreover, the inverted dual-label assay provides a highly flexible and easily implementable technique for distinguishing between strain-specific and cross-reactive B cell responses and has broad applications in translational vaccine research against pathogens that undergo antigenic drift. Full article

We recently identified the U1 small nuclear ribonucleoprotein (U1-snRNP) antibodies in patients with Guillain–Barré syndrome (GBS), which is associated with the breakdown of the blood–nerve barrier (BNB). The objective of this study was to clarify the clinical significance of U1-snRNP antibodies in patients with GBS and its variants. We measured U1-snRNP antibodies using an enzyme-linked immunosorbent assay from the serum samples of patients with GBS (n = 106), Miller Fisher syndrome (MFS) (n = 24), and MFS/GBS overlap syndrome (MFS/GBS, n = 8). We compared the clinical characteristics of U1-snRNP positive and U1-snRNP negative GBS patients (n = 106). The cerebrospinal fluid (CSF)/serum albumin quotient (QALB)/QALBLIM [calculated as(age/15) + 4)] was calculated. The prevalence of U1-snRNP antibody positivity was 39% (41/106) in GBS, 0% (0/24) in MFS, and 50% (4/8) in MFS/GBS. The rate of U1-snRNP antibody positivity in the GBS and MFS/GBS groups was significantly higher than that in the MFS group. Levels of CSF proteins and QALB/QALBLIM were higher in U1-snRNP antibody-positive GBS than in U1-snRNP antibody-negative GBS among all GBS patients, as well as GBS patients with a preceding Campylobacter jejuni infection or AIDP. In conclusion, the U1-snRNP antibody-positive GBS group had a more severe breakdown of the BNB in U1-snRNP antibody-positive GBS patients than in U1-snRNP-negative GBS patients. The presence of U1-snRNP antibodies may be a clinical biomarker for predicting the progression of MFS to MFS/GBS. Full article

Background: Children with IBD are at increased risk of suboptimal maintenance of vaccine-induced immunity, particularly when the MMR vaccination course is incomplete before diagnosis and initiation of immunosuppressive therapy. We conducted a prospective study to evaluate the durability of antibody responses to measles, mumps, and rubella in pediatric IBD patients and to determine how completeness of MMR vaccination influences long-term antibody persistence over 12 months. Methods: Sixty children with IBD were included. Demographic characteristics, clinical disease activity (PUCAI/PCDAI), inflammatory markers (CRP, ESR), and fecal calprotectin were extracted from electronic medical records. Vaccination completeness was ascertained from documented immunization history. Serum antibodies to measles, rubella, and mumps were measured at baseline and after 12 months. Seroprotection was defined using standard laboratory thresholds. Antibody decay over time was assessed with paired non-parametric tests, and time to loss of seroprotection was analyzed using Cox proportional hazards models. In addition, Bayesian ANOVA modeling was applied to quantify evidence for differences in antibody concentrations and decay kinetics according to vaccination status. Results: Overall, 66.7% of patients had completed the full MMR vaccination course. At baseline, seroprotection rates were 48.3% for measles, 76.7% for rubella, and 70% for mumps. After 12 months, median antibody concentrations declined significantly for all three antigens. Corresponding seroprotection rates changed to 46.7% for measles (p = 0.414), 70% for rubella (p = 0.046), and 66.7% for mumps (p = 0.157). Incomplete MMR vaccination was identified as a major modifiable risk factor for accelerated antibody waning in children with IBD. Cox regression demonstrated that incompletely vaccinated patients had a 2.13-fold higher risk of losing measles seroprotection (95% CI 1.07–4.24; p = 0.032), a 5.27-fold higher risk for rubella (95% CI 1.86–14.95; p = 0.002), and a 4.82-fold higher risk for mumps (95% Cl 1.68–13.85; p = 0.004). Bayesian analyses provided decisive evidence that vaccination completeness strongly influences baseline antibody levels. Conclusions: Incomplete MMR vaccination is associated with markedly reduced durability of vaccine-induced immunity to measles, mumps, and rubella in children with IBD. These findings underscore the need for systematic prevaccination screening, timely completion of age-appropriate vaccination before initiation of immunosuppressive therapy when feasible, and individualized serological monitoring to identify patients at highest risk of vaccine-preventable infections. Full article

Background: Extracranial arteriovenous malformations (eAVMs) are aggressive vascular anomalies consisting of abnormal blood vessels (BVs) and multiple other cell types, including macrophages. Although inflammation and the presence of immune cells are characteristics of eAVMs, the contribution of macrophage polarization to eAVM pathophysiology is unknown. Methods: In this study, pediatric eAVM tissues and adjacent control tissues were analyzed using immunohistochemistry (IHC) and immunofluorescence (IF) to assess M1 and M2 macrophage localization, loss of endothelial CD31 expression, and expression of the immune-regulatory protein PDL-1. In addition, serum samples from eAVM patients were analyzed using a human inflammation antibody array to profile cytokines and other circulating factors associated with M2 macrophage and immunosuppressive microenvironment. Results: eAVM tissues demonstrate accumulation of M2-polarized macrophages around abnormal CD31^−ve BVs, while M1 macrophages were primarily associated with normal appearing CD31^+ve vessels. eAVM tissues demonstrated increased expression of PD-L1 in regions enriched with M2 macrophages, which were absent in paired control tissues. Serum analysis revealed increased levels of circulating factors associated with M2 macrophages and immune suppression, including PDGF-BB, IL-4, and IL-16. Conclusions: These findings suggest that CD31^−ve vessels in eAVMs are associated with enrichment of M2 macrophages and a microenvironment suggestive of localized immune regulation. These observations are hypothesis-generating and warrant validation in larger patient cohorts and future mechanistic studies. Full article

Background/Objectives: Parkinson’s disease (PD) exhibits marked sexual dimorphism, with a higher incidence and earlier onset in men than in women. However, the impact of biological sex on systemic molecular alterations in PD remains poorly understood. This pilot study aimed to identify sex-specific circulating signatures associated with PD. Methods: Serum samples from a selected cohort of PD patients and healthy controls (HC) of both sexes were analyzed using an integrated biochemical and ¹H NMR-based metabolomic approach. Oxidative stress markers, antioxidant proteins, inflammatory mediators, matrix metalloproteinases, α-synuclein species, and circulating antibodies were evaluated. Results: This analysis indicated that, while global oxidative stress markers were unchanged, sex-related differences in antioxidant pathways were observed as suggested by the reduced Nrf2 expression observed in PD females and increased IL-6 levels, above all in male PD patients. MMP3 levels were significantly higher in female PD patients compared with males. Male patients showed higher levels of 52 kDa protease-resistant α-synuclein species, while females exhibited increased antibody titers against both monomeric and aggregated forms. Metabolomic profiling suggested a disease-associated metabolic remodeling in PD, with distinct sex-related metabolic signatures and a more pronounced and widespread metabolic dysregulation in males. Conclusions: These findings suggest that biological sex may contribute to systemic molecular heterogeneity in PD, with trends indicating more pronounced inflammatory and metabolic alterations in males and distinct immune-related responses in females. Given the exploratory nature of the study and the limited sample size, these observations should be interpreted cautiously and require validation in larger, independent cohorts. Nevertheless, the results support the importance of considering sex-related molecular differences in future biomarker studies and precision medicine approaches for PD. Full article

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome (NS). The remission rate of MN remains limited, and effective strategies for refractory MN are not established. We present the case of a 49-year-old Japanese woman with severe NS caused by MN. Kidney biopsy revealed glomerular basement membrane thickening with granular deposition of immunoglobulin G (IgG) and complement component 3. IgG subclass analysis showed predominant IgG1 deposition, with weak IgG2 and IgG3 deposition. Phospholipase A2 receptor (PLA2R) deposition was equivocal in the first kidney biopsy and negative in the second. Serum anti-PLA2R antibody was not detected. Electron microscopy revealed subepithelial, subendothelial, and mesangial electron-dense deposits. Detailed screening revealed no significant abnormalities other than appendiceal findings, suggesting secondary MN associated with appendiceal infection. Although combined therapy with prednisolone, cyclosporine, rituximab, and low-density lipoprotein apheresis was administered during the first 6 months, remission of MN was not achieved. During dialysis, initiated because of kidney failure, long-term multidisciplinary management, including control of appendiceal infection and inflammation and initiation of angiotensin II receptor blocker therapy, ultimately led to remission of MN and discontinuation of dialysis. Overall, even refractory MN requiring dialysis may have a reversible clinical course with careful conservative management and long-term follow-up. Full article

Background/Objectives: Vesicular Stomatitis Virus (VSV)-vectored vaccines represent a versatile platform for the development of vaccines against infectious diseases. Replication-competent recombinant VSV vectors in which the native glycoprotein (G) is replaced with a heterologous antigen (rVSVΔG) are widely used and have demonstrated clinical success. In addition to antigen-specific responses, these vaccines induce humoral immunity directed against vector components, which primarily reflects vector exposure and contributes to the overall characterization of vaccine-induced immunity. Standardized assays for quantifying such vector-directed responses are therefore of increasing importance. Methods: We developed and qualified a quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of human IgG antibodies against VSV-Nucleoprotein (N). Assay development included optimization of antigen coating, blocking conditions, and detection reagents. A 10-point standard curve was established using pooled human serum, and assay performance was evaluated by assessing dynamic range, sensitivity, cut point, dilutional linearity, precision, robustness, and sample stability. Results: The optimized assay utilized a coating concentration of 2 μg/mL VSV-N antigen (100 ng/well) and 1% casein as the blocking buffer. The assay demonstrated a dynamic range of 0.33–41.66 arbitrary units per milliliter (AU/mL) with excellent curve fit (R² > 0.996). The cut point was established at an OD₄₅₀ of 0.286. Precision across intra-assay, inter-assay, and inter-operator evaluations met predefined acceptance criteria (≤25% CV). The assay was robust across different plate washers and readers and maintained performance following up to three freeze–thaw cycles. Conclusions: This study describes a robust and reproducible ELISA for quantifying anti-VSV-N IgG responses. The assay provides a fit-for-purpose tool for assessing vector-directed humoral immunity and supports standardized immunogenicity evaluations across VSV-vectored vaccine studies. Full article

Background: Vitamin D is involved not only in calcium–phosphate homeostasis but also in immune and endothelial regulation. Vitamin D deficiency has been suggested to worsen disease activity in systemic lupus erythematosus (SLE). Environmental and lifestyle factors, including seasonal sun exposure, smoking, diet, and supplementation, may influence vitamin D status and disease manifestations. This study aimed to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels, disease activity, and anti-double-stranded DNA (anti-dsDNA) antibody titers in patients with SLE, taking selected lifestyle and environmental factors into account. Methods: Serum 25(OH)D concentrations, SLE disease activity assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and anti-dsDNA antibody titers were measured in patients with SLE and healthy controls. Blood samples were collected during sunny (April–September) and non-sunny (October–March) months. Information on vitamin D supplementation, smoking status, and dietary habits was obtained using a structured questionnaire. Associations between vitamin D status, disease activity, anti-dsDNA seropositivity, season of blood collection, supplementation, smoking, and diet were analyzed statistically. Results: Patients with SLE had significantly higher mean serum 25(OH)D levels than controls, mainly due to frequent vitamin D supplementation. No significant associations were observed between serum 25(OH)D levels and SLEDAI-2K scores or anti-dsDNA antibody positivity. Seasonality, smoking status, and adherence to special diets were not significantly related to disease activity or anti-dsDNA seropositivity. Vitamin D supplementation was strongly associated with sufficient 25(OH)D levels but did not translate into reduced disease activity or lower anti-dsDNA prevalence. Conclusions: Serum 25(OH)D concentration was not associated with clinical or immunological activity of SLE in this cross-sectional study, despite effective correction of deficiency through supplementation. These findings likely reflect the heterogeneity of SLE and the limitations of single time-point assessments, although regular monitoring and individualized vitamin D supplementation may still be considered in SLE care, particularly in the context of recommended photoprotection. Full article

Outbreaks of avian infectious bronchitis virus (IBV) often occur in vaccinated flocks. The antibody-dependent enhancement (ADE) has been proposed as a potential mechanism underlying coronavirus vaccine failure. However, this hypothesis has yet to be substantiated in flocks. This study demonstrates ADE occurrence in IBV (gamacoronavirus) in vitro and in vivo. Using the SPF chicken host model, primary infection with an O-glycosylation-modified attenuated strain enhanced pathogenesis upon secondary homologous/heterologous virulent challenge, increasing morbidity/mortality (≥30%), pathological lesions, and viral loads. Notably, sequentially attenuated infections also induced ADE, suggesting live attenuated vaccine risks. The immune serum raised against the O-glycosylation-modified attenuated strain was also pre-mixed with the challenge strain, and the mixtures were then inoculated into target cells, non-susceptible macrophage cells, or a co-culture of both cell types. The serum-virus complexes replicated poorly in macrophages, yet immune cells amplified the expression of inflammatory factors and ADE-mediated viral replication in target cells, indicating a significant promoting role of immune cells in this process. The concentrations of complement component C3 and neutralizing antibodies in the immune serum were also measured, and results showed that the induction of this ADE is associated with high complement component C3 and low neutralizing antibody titers. These findings highlight risks for vaccines and antibody-based therapeutic strategies of coronavirus infection. Full article

Background: Primary cells derived from connective tissues contain mesenchymal stem/stromal cell (MSC)–like progenitors with chondrogenic potential relevant for cartilage repair. However, donor- and tissue-specific variability and the lack of robust, high-content analytical methods limit their translational use. Objectives: This study aimed to develop and optimize a high-content imaging workflow for quantitative evaluation of chondrogenesis in three-dimensional (3D) pellets derived from primary cells. Methods: Primary human cells isolated from cartilage were chondrogenically differentiated in vitro. A systematic optimization of immunofluorescence staining parameters was performed, including staining platform, enzymatic matrix digestion, non-specific site blocking, membrane permeabilization, and nuclear counterstaining. Type II collagen was detected using an Alexa Fluor 488–conjugated antibody, and pellets were analyzed using high-content non-confocal imaging. Fluorescence intensities were adjusted to the pellet area to account for size-dependent effects. Results: Staining directly in imaging plates enabled streamlined high-content analysis. Controlled pepsin-mediated matrix digestion markedly enhanced antibody penetration, while excessive digestion compromised pellet integrity. Extended bovine serum albumin blocking improved type II collagen signal intensity and homogeneity. Triton X-100 permeabilization increased detection sensitivity but occasionally induced structural disruption in weakly organized control pellets. The optimized protocol enabled clear discrimination between chondrogenic pellets and controls, with approximately threefold higher type II collagen signal in chondrogenic samples. Conclusions: This study establishes a high-content imaging–based workflow for quantitative assessment of 3D chondrogenesis from primary cells. The approach provides a rapid, scalable platform with direct relevance for in vitro screening, potency testing, and quality control in cartilage-oriented advanced therapy development. Full article

Pernicious anemia (PA) represents a significant diagnostic challenge in neuropsychiatric patients due to its subtle and variable presentation. While PA is traditionally associated with clinical and biochemical manifestations of anemia, many patients, particularly those with neuropsychiatric symptoms, may have normal hematologic parameters, delaying recognition and appropriate treatment. Neurological and psychiatric symptoms, ranging from cognitive impairment and mood disorders to subacute combined degeneration (SCD) of the spinal cord, can precede hematologic abnormalities, leading to misdiagnosis or inappropriate management. The lack of a definitive gold standard test for cobalamin deficiency (CD) further complicates identification. Commonly used biomarkers, such as serum cobalamin, methylmalonic acid (MMA), homocysteine (Hcy), intrinsic factor antibodies (IFAs), and parietal cell antibodies (PCAs), each have limitations in diagnosing PA, especially in the absence of overt anemia. The variability in diagnostic criteria and cutoff values across studies adds to the challenge of achieving early and accurate diagnosis. This article reviews the complexities of diagnosing PA in neuropsychiatric patients, evaluates the limitations of current diagnostic methods, and emphasizes the need for a more comprehensive, standardized approach to early detection and treatment. Combining clinical awareness with improved biomarker interpretation is essential for preventing irreversible neurological damage and improving patient outcomes. Improved diagnostic protocols and further research are essential to optimize detection and minimize the risk of long-term neurological damage. Full article

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes severe illness in livestock and humans, with significant economic and health repercussions. Mauritania is considered an RVF focus in West Africa. A cross-sectional survey was conducted in 2023 in 12 of Mauritania’s 15 provinces. Serum samples from 849 small ruminants (428 goats and 421 sheep) were analyzed by ELISA for IgG and IgM antibodies against RVF virus. Logistic regression analyses were performed to assess associations between seropositivity and species, age, sex, season, and geographic location. In total, 14.1% of the animals tested were positive for anti-RVFV IgG antibodies. There was no association between anti-RVFV IgG positivity and the ruminant species, the sex, the age and the season. Hodh El Gharbi had the highest seroprevalence (40.5%), followed by Adrar (19.8%) and Tagant (19.7%). The lowest levels were recorded in Tiris Zemmour (2%) and Inchiri (3%). Only two animals tested positive for IgM, suggesting limited recent viral activity. This nationwide survey confirms widespread exposure of small ruminants to RVFV in Mauritania. Strengthening longitudinal serological monitoring and integrating ecological and entomological data within the “One Health” approach will be essential to preventing future epidemics and protecting animal and human health. Full article

Background: The COVID-19 pandemic exposed critical gaps in pandemic preparedness and highlighted the need for vaccine platforms capable of rapid adaptation. Outer membrane vesicle (OMV)-based platforms utilizing vesicles derived from genetically detoxified Neisseria meningitidis serogroup B (Nm-nOMV) represent a promising plug-and-play approach. Methods: This Phase I, first-in-human, randomized, double-blind, placebo- and OMV-controlled trial, evaluated safety, tolerability, and immunogenicity of intranasally administered OMVs combined with SARS-CoV-2 Spike protein in healthy SARS-CoV-2 seropositive adults aged 18–55 years. Forty participants were enrolled across two cohorts: a low-dose cohort receiving 140 μg OMV/70 μg Spike (OMV + Spike, n = 13; OMV alone, n= 3; Placebo, n = 5) and a high-dose cohort receiving 280 μg of OMV/140 μg of Spike (OMV + Spike, n = 13; OMV alone, n = 3; Placebo, n = 3), administered on Days 1 and 22. Safety was assessed through adverse events, vital signs, laboratory parameters, ECG, and pulse oximetry. Immunogenicity was evaluated via systemic SARS-CoV-2 neutralizing antibodies, antigen-specific antibodies (IgG and IgA), and mucosal antibodies (IgA in nasal wash). Results: Intranasal administration of OMVs combined with SARS-CoV-2 Spike protein was safe, well-tolerated, and immunogenic. No serious adverse events were reported, and adverse events were predominantly mild and transient. Dose-dependent increases in systemic and mucosal immune responses were observed, with statistically significant enhanced serum IgG and nasal wash IgA antibodies in the high-dose group. Conclusions: The current clinical data confirm key aspects of the preclinical profile, which demonstrate the potential of the Nm-nOMV platform as a strong adjuvant for mucosal vaccines. These findings support the broader application of the Nm-nOMV vaccine platform in pandemic preparedness. Full article

Background: Adult susceptibility to diphtheria and tetanus may increase as vaccine-induced immunity wanes, yet repeated population-based serosurveillance data in China are limited. Methods: We analyzed annual serosurveys conducted in Pudong New Area, Shanghai, China, from 2017 to 2025 among healthy adults aged 20–49 years. Diphtheria and tetanus IgG concentrations were measured by ELISA. Seroprotection was defined as antibody concentration ≥0.1 IU/mL. Antibody concentrations were further categorized as <0.01, 0.01–<0.1, 0.1–<1.0, and ≥1.0 IU/mL, and geometric mean concentrations (GMCs) were calculated. Multivariable logistic regression models were fitted to assess factors associated with non-protection, including survey year, age group, and household registration. Sensitivity analyses excluding the 2018 survey year were conducted. Results: A total of 2376 serum samples were included. Overall seroprotection was 21.46% for diphtheria and 13.80% for tetanus. The proportion protected against both antigens was 9.05%, while 73.78% showed concurrent non-protection against both antigens. The overall GMC was 0.032 IU/mL (95% CI: 0.030–0.034) for diphtheria and 0.018 IU/mL (95% CI: 0.017–0.019) for tetanus. Concentrations ≥1.0 IU/mL were uncommon for both antigens. Adults aged 40–49 years had higher odds of non-protection than those aged 20–29 years for diphtheria (OR: 2.43, 95% CI: 1.85–3.21) and tetanus (OR: 2.94, 95% CI: 2.11–4.13). Non-local residents also had higher odds of non-protection than local residents for diphtheria (OR: 1.55, 95% CI: 1.24–1.93) and tetanus (OR: 2.81, 95% CI: 2.15–3.69). Seroprotection varied across survey years, with a marked nadir in 2018. Sensitivity analyses excluding 2018 attenuated most year-specific associations, whereas age- and residence-related differences persisted. Conclusions: Healthy adults aged 20–49 years in Pudong showed low seroprotection and low GMCs against both diphtheria and tetanus, with a high proportion concurrently non-protected against both antigens. These findings highlight a persistent adult immunity gap and support further evaluation of adult booster strategies and enhanced serosurveillance. Full article