Search Results (818)

Background/Objectives: Celiac disease (CD) is a chronic immune-mediated disorder associated with a broad spectrum of extraintestinal manifestations, including hematological abnormalities. Although anemia and micronutrient deficiencies are well recognized, neutrophil morphological abnormalities have not been systematically investigated in pediatric CD; this study aimed to evaluate peripheral blood smear findings in children with CD compared with healthy controls. Methods: This retrospective case–control study included 70 children with CD and 74 healthy controls; demographic characteristics, anthropometric measurements, hematological and biochemical parameters, and peripheral blood smear findings were analyzed and compared between groups. Results: Children with CD had significantly higher frequencies of underweight status (15.7% vs. 2.7%) and short stature (21.4% vs. 1.4%) than controls. Most hematological and biochemical parameters were comparable between groups, except for platelet counts and ferritin levels, which differed significantly. Pseudo-Pelger–Huët anomaly (PPHA) was identified in 87.1% of children with CD versus 8.1% of controls (p < 0.001), and neutrophil dysplasia was observed in 52.9% versus 1.4%, respectively (p < 0.001). After adjustment for age and sex, CD remained strongly associated with PPHA (adjusted OR 81.19, 95% CI 28.65–278.45), neutrophil dysplasia (adjusted OR 93.85, 95% CI 18.46–1724.96), and the combined presence of both abnormalities (adjusted OR 79.89, 95% CI 15.86–1461.89) (all p < 0.001). ROC analysis demonstrated excellent discrimination between CD and controls (AUC = 0.924; sensitivity = 90.0%; specificity = 91.9%). Within the CD cohort, PPHA and dysplasia were not associated with celiac antibody positivity, gluten-free diet adherence, vitamin D deficiency, or comorbid conditions. Conclusions: To our knowledge, this is the first study to systematically evaluate peripheral blood smear morphology in pediatric CD, demonstrating a remarkably high prevalence of PPHA and neutrophil dysplasia. These findings suggest that neutrophil morphological abnormalities may represent an underrecognized hematological manifestation of pediatric CD, potentially reflecting chronic immune-mediated alterations in granulopoiesis. Further prospective studies are needed to clarify their pathogenesis, clinical significance, and reversibility following long-term gluten-free diet treatment. Full article

Hemoglobin (Hb) and its glycated variant (HbA1c) are essential clinical biomarkers for diagnosing anemia, acute hemorrhage, and long-term glycemic control. The growing demand for decentralized point-of-care (POC) testing has accelerated the development of rapid, inexpensive, and portable electrochemical sensing platforms. These technologies exploit the intrinsic redox activity of the heme prosthetic group, yet achieving efficient direct electron transfer (DET) remains a fundamental challenge because the electroactive iron center is deeply embedded within the globin structure. This review critically examines recent advances in electrochemical Hb sensing, tracing the evolution of electrode architectures from conventional carbon substrates to nanostructured materials, including graphene, MXenes, metal–organic frameworks (MOFs), and molecularly imprinted polymers (MIPs). We compare the advantages and limitations of non-enzymatic biomimetic platforms and affinity-based sensing strategies, including aptamer- and antibody-based biosensors, with emphasis on electron-transfer efficiency, molecular selectivity, analytical performance, and suitability for POC implementation. Beyond analytical performance, we evaluate the principal barriers to clinical translation, including biofouling, whole-blood matrix effects, viscosity-dependent mass transport, manufacturing scalability, and the persistent gap between validation in synthetic media and performance in clinical samples. Finally, we discuss emerging applications in wearable menstrual health monitoring and ingestible gastrointestinal bleeding sensors, highlighting the integration of advanced electrochemical materials with miniaturized electronics as a pathway toward practical, consumer-oriented diagnostics. Full article

Background/Objectives: Humans are primarily infected by two distinct seasonal influenza A virus (IAV) subtypes, A(H1N1)pdm09 and A(H3N2). Because IAV mutates rapidly, it continuously escapes existing protective antibodies. However, repeated exposure to these evolving strains increases the diversity of virus-specific memory B cell (MBC) population. To investigate the extent of this diversity and cross-reactivity of IAV- specific immunity in adults, and its possible impact on emerging strains, we analyzed the hemagglutinin (HA)-specific MBC repertoire of an adult frequently immunized with seasonal vaccines. Methods: High-throughput single-cell sequencing of HA probe-positive MBCs collected from an individual with repeated seasonal influenza vaccination was performed. Monoclonal antibodies (mAbs) from multicell clonotypes were tested for HA binding and influenza virus neutralization. Results: Two clonotypes were identified that bound to both A(H1) and A(H3) HAs from strains circulating before and after the season of blood collection. Both clonotypes neutralized A(H3N2) strains, while one also neutralized A(H1N1)pdm09 strains. Notably, these cross-group binders showed affinity for A(H5), A(H7) and A(H9) avian influenza HAs and neutralized bovine A(H5N1) IAV. Conclusions: Our findings suggest that seasonal vaccination can support pre-existing cross-reactive B-cell immunity in some individuals. This underscores the importance of studying influenza-specific MBC repertoires across diverse populations to better understand immune dynamics and improve vaccine design. Full article

Clinical outcomes for brain cancer are often poor because the blood–brain/tumor barrier hinders effective drug delivery to malignant tissue. Glioblastoma, the most common primary brain malignancy in adults, has an average survival of approximately fourteen months. Here, we discuss novel strategies that our research group and others are developing to deliver chemotherapy to the brain via the nasal cavity. Although significant hurdles remain, intranasal delivery holds substantial promise for improving outcomes for patients with brain cancer. Intranasal delivery is noninvasive, permits repeated dosing, and has been shown to enable direct nose-to-brain transport that bypasses the blood–brain barrier. Challenges such as accurately targeting drugs to the appropriate region of the nasal cavity at therapeutically relevant doses, while maintaining reproducibility, make this cutting-edge approach a regulatory challenge. The prolonged path to clinical translation discourages many researchers from pursuing this potentially life-saving strategy. Nevertheless, preclinical studies demonstrate that intranasal delivery can achieve up to ten-fold higher concentrations of select drugs in the brain. Cancer chemotherapeutics span a wide range of molecular formats, from small molecules to 150-kilodalton antibodies. Accordingly, delivery strategies must be carefully matched to the molecular properties of each therapeutic. Here, we focus on the intranasal delivery of small molecule inhibitors using nanomaterial-based platforms, including aerosols, lipids, gold nanoparticles, gels, emulsions, fibers, and their combinations. Ultimately, we hope that intranasal delivery approaches will be translated to provide patients with better therapeutic outcomes. Full article

Safe transfusion depends on rapid, accurate ABO typing, yet reference methods require centrifuges and instrumentation unavailable at the point of need. Here, a paper-based ABO-RhD typing device built on a covalent, optically silent surface chemistry is reported. Aminosilane (APTES) and epoxysilane (GPTMS) functionalisation of Whatman cellulose was compared by water contact angle, energy-dispersive X-ray spectroscopy (SEM-EDS) and infrared spectroscopy (FT-IR) across two paper grades, three silane concentrations (5, 10 and 20% v/v) and three reaction times (1–6 h). APTES produced a strongly hydrophobic layer that impeded aqueous wicking, and its glutaraldehyde activation generated a red-brick chromophore incompatible with a red-channel readout. GPTMS coupled antibodies in a single mild step, without a crosslinker or visible chromophore, while preserving wicking. GPTMS (10% v/v, 3 h, Whatman No. 4) with a six-cycle 100 µL saline wash was selected; antibodies were immobilised in a four-zone layout (anti-A, anti-B, anti-D and control) within a 3D-printed two-compartment housing that traps agglutinated cells while free cells wash through. On 80 EDTA clinical blood samples (20 each of groups A, B, AB and O) the device classified every sample correctly (accuracy 100%; 95% confidence interval 95.4–100%), with visual and instrumented reads in full agreement. All samples were RhD-positive, so the anti-D channel is validated here for the positive call. Full article

Bacterial tick-borne pathogens (TBPs) have been reported in Latin America, but information on their prevalence in cattle and dogs in Bolivia are scant. In the present survey, blood serum samples from 95 cattle and 67 dogs living in different communities of Bolivian Chaco, a region in southeastern Bolivia, were tested for antibodies against Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato (s.l.), Coxiella burnetii, Ehrlichia canis, and Rickettsia rickettsii. Indirect immunofluorescence assays detected 54/95 (56.84%) cattle sera positive to one or more pathogens: 29/95 (30.5%) to A. phagocytophilum, 27/95 (28.42%) to R. rickettsii, 5/95 (5.26%) to C. burnetii; all sera were negative to B. burgdorferi s.l. Among canine sera, 11/67 (16.41%) were positive to at least one pathogen: 2/67 (2.98%) to C. burnetii, 3/67 (4.48%) to E. canis, 6/67 (8.95%) to R. rickettsii; all sera were negative to A. phagocytophilum and B. burgdorferi s.l. To the best of our knowledge, this is the first serological survey investigating exposure to multiple TBPs in cattle and dogs from the Bolivian Chaco. Our findings suggest the circulation of A. phagocytophilum, E. canis, C. burnetii, and Spotted Fever Group Rickettsia among the animals living in this area. The results are relevant because these pathogens pose a significant threat to human and animal health and may result in substantial economic losses. Full article

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

Background: Red blood cell (RBC) antibody screening in blood donors is a key component of transfusion safety. However, reported prevalence and antibody specificities vary widely across studies, and a consolidated global estimate remains limited. This study aimed to quantify the prevalence of RBC antibody detection among blood donors, identify factors associated with variation in reported prevalence, and summarize antibody specificities. Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed, MEDLINE, Embase, Scopus, and Google Scholar were searched from inception to 27 August 2025 for observational studies reporting RBC antibody detection in blood donors. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data. Pooled prevalence estimates were synthesized using random-effects models. Subgroup analyses, meta-regression, leave-one-out sensitivity analyses, and publication-bias assessments were performed. Associations between ABO blood group and RBC antibody detection were summarized using pooled odds ratios. The review protocol was registered in PROSPERO (CRD420251181987). Results: Forty-one studies comprising 43 reports and 3,561,088 blood donors from 18 countries were included. The pooled prevalence of RBC antibody detection was 0.2% (95% CI: 0.2–0.3%), with substantial between-study heterogeneity (I²: 99.61%) and a 95% prediction interval of 0.0–1.4%. Prevalence was higher in female donors than in male donors (0.5% vs. 0.1%). Publication year was inversely associated with reported prevalence, although temporal and methodological effects could not be separated. An exploratory analysis based on six studies showed higher estimated odds of antibody detection among blood group AB donors (OR: 1.20, 95% CI: 1.07–1.34). Among clinically significant antibodies, Rh and Kell specificities were predominated. Anti-Mi^a was prominent in Southeast Asian populations. Conclusions: RBC antibody detection among blood donors was uncommon overall but varied considerably across settings. Interpretation is limited by substantial methodological heterogeneity, uneven geographic representation, and incomplete reporting of donor characteristics. The pooled estimate should be interpreted as an international benchmark rather than a uniform prevalence applicable to individual blood services. This large-scale synthesis may inform context-specific donor antibody screening, confirmatory testing, component management, and hemovigilance policies. Full article

The largemouth bass (Micropterus salmoides) is persistently threatened by Micropterus salmoides rhabdovirus (MSRV) and largemouth bass ranavirus (LMBV), highlighting the need for combined immunization strategies. Here, a bivalent DNA vaccine pEGFP-G-MCP was constructed by concatenating the highly immunogenic fragments of MSRV glycoprotein (MSRV-G) and LMBV main capsid protein (LMBV-MCP) using a flexible linker peptide, and its immunogenicity and protective effect were systematically evaluated. Fish were immunized by intramuscular injection of 200 ng of plasmid on day 1, followed by a booster immunization on day 8. Blood and tissues were collected at 10, 20, and 30 d post-last immunization. The results showed that pEGFP-G-MCP immunization induced G- and MCP-specific antibodies and upregulated the expression of immunity-related genes. The bivalent vaccine achieved a relative percent survival (RPS) of 93.3% against MSRV and 90.0% against LMBV, which were higher than those of the monovalent vaccine groups. Additionally, the bivalent vaccine reduced viral mRNA and alleviated pathological damage in MSRV- or LMBV-infected fish. These results indicate that pEGFP-G-MCP confers immune protection against MSRV and LMBV, providing a foundation for combined prevention and control of MSRV and LMBV. Full article

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

Background: Primary hyperparathyroidism (PHPT) is usually caused by parathyroid tumors, resulting in hypercalcemia due to excessive PTH secretion. While disease severity correlates with calcium blood levels, the molecular mechanisms driving clinical variability remain unclear. The role of the calcium-sensing receptor (CaSR), the vitamin D receptor (VDR) and parathyroid cells mitochondrial activity in the pathogenesis of hyperparathyroidism is of particular interest. Methods: This retrospective study included 96 patients with PHPT who underwent parathyroidectomy. Patients were stratified into four groups according to the baseline albumin-corrected serum calcium assessed at diagnosis, before the initiation of calcimimetic therapy (≤2.8; 2.8 < Ca corr. ≤ 3.0; 3.0 ≤ Ca corr. < 3.5; Ca corr. ≥ 3.5 mmol/L). Immunohistochemical expression (IHC) was estimated using CaSR, VDR, and antimitochondrial antibodies (AMA). Antibodies to VDR (GeneTex), CaSR (5C10, GeneTex), AMA (113-1, BioGenex) were used. Kidney tissue served as a positive control for CaSR and VDR antibodies, and liver tissue was used as a positive control for AMA. Statistical analysis was performed using the Statistica v. 13.3 software package (TIBCO Software Inc., Palo Alto, CA, USA; 2017). Results: Strong CaSR expression was observed in 95.8% of tumors, whereas VDR expression was reduced in 46.9%. AMA staining was heterogeneous, with high reactivity in oncocytic cells. No significant differences in CaSR, VDR, or AMA expression were found across groups with different hypercalcemia severity. No significant associations were identified between IHC marker expression and parameters of calcium-phosphorus metabolism, as well as cinacalcet treatment response. Conclusions: Despite their established roles in parathyroid regulation, CaSR and VDR expression did not correlate with hypercalcemia severity in PHPT. These findings suggest that alternative molecular mechanisms, rather than receptor expression levels, contribute to clinical heterogeneity. Further research is required. Full article

Porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (Mhp) are major contributors to the porcine respiratory disease complex. Although PCV2-Mhp bivalent inactivated vaccines are useful for simultaneous disease control, their immunogenicity may be improved by adjuvant optimization. This study evaluated a composite adjuvant consisting of porcine interleukin-2 (IL-2), IL-4, IL-6 and MnJ(beta), a colloidal manganese adjuvant, in an initial murine immunogenicity model. Thirty female Kunming mice were assigned to three groups (n = 10/group): bivalent antigen plus IL-2/IL-4/IL-6/MnJ(beta), bivalent antigen plus MnJ(beta), or phosphate-buffered saline. Body weight, complete blood count, peripheral blood T- and B-cell subsets, PCV2-specific IgG and Mhp-specific indirect hemagglutination titers were monitored after primary and booster immunization. The composite formulation did not suppress body-weight gain or induce sustained abnormalities in erythrocyte- or platelet-related indices. WBC, neutrophil, lymphocyte and monocyte counts were elevated in group A at days 7 and 28 post-primary immunization, indicating transient immune activation. Day-56 flow cytometry indicated increased CD19+IgM-IgD- B-cell and effector/memory T-cell-associated responses. PCV2-specific IgG increased from day 14 onward. At day 56, the OD450 value in group A reached 1.532 ± 0.006, compared with 1.095 ± 0.004 in group C1 and 0.102 ± 0.002 in group C2, corresponding to approximately 1.40-fold and 15.09-fold higher levels than the MnJ(beta)-adjuvanted and PBS control groups, respectively. Mhp-specific IHA titers were also maintained at high levels after booster immunization; at day 56, group A showed a log2 endpoint titer of 13.00 ± 0.00, corresponding to a GMT of 1:8192, whereas group C1 showed a log2 endpoint titer of 12.00 ± 0.00, corresponding to a GMT of 1:4096, and group C2 remained negative. These results indicate that the IL-2/IL-4/IL-6/MnJ(beta) composite adjuvant demonstrates potential for improving antibody and peripheral lymphocyte responses to PCV2-Mhp bivalent antigen, but protective efficacy must be confirmed in target-species challenge studies. 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/Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) describes the rapid onset of obsessive–compulsive symptoms or severe food restriction, accompanied by neuropsychiatric or somatic features that are not better explained by another disorder. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a related, more narrowly defined construct in which symptoms are temporally associated with group A Streptococcus infection. This review examines clinical symptoms, infectious associations, proposed immune mechanisms, biomarker limitations, and treatment strategies for infection-associated PANS/PANDAS. Methods: A structured narrative search of PubMed/MEDLINE, Embase, the Cochrane Library, Google Scholar/publisher-indexed literature, ClinicalTrials.gov, and reference lists was performed up to 16 June 2026. Original cohorts, case series, systematic reviews, narrative reviews, consensus guidance, mechanistic studies, and registered prospective studies were prioritized. The review was not designed as a PRISMA-ScR scoping review; however, the methods were expanded to improve transparency and align with SANRA principles. Results: Group A Streptococcus remains the best characterized infectious association, although prospective studies have not uniformly demonstrated a consistent temporal relationship between streptococcal infection and neuropsychiatric exacerbations. Parent-reported surveys and case-based literature also describe temporal associations with Mycoplasma pneumoniae, influenza-like illnesses, upper respiratory infections, Borrelia burgdorferi, Epstein–Barr virus, and SARS-CoV-2. Proposed mechanisms include molecular mimicry, anti-D1R and anti-D2R antibodies, other antineuronal antibodies, calcium/calmodulin-dependent protein kinase II signaling, blood–brain barrier vulnerability, cytokine and Th17 effects, neuroinflammatory amplification, basal ganglia/CSTC circuit dysfunction, and gut–oral–brain immune interactions. None currently provides a definitive diagnostic biomarker. Conclusions: Infection-associated PANS is best approached as a clinically defined, heterogeneous neuroimmune presentation that requires rigorous differential diagnosis, multidisciplinary care, cautious treatment escalation, prospective biomarker validation, and large, multicenter treatment trials. Full article

Background/Objectives: Polyethylene glycol (PEG) is widely used to enhance the stability and pharmacokinetics of nanomedicines, including lipid nanoparticle (LNP)-based mRNA vaccines. However, both pre-existing and vaccine-induced anti-PEG antibodies may compromise the efficacy and safety of PEGylated therapeutics. Methods: In this study, we analyzed the specificity and avidity of anti-PEG antibodies in human blood donor samples from Unvaccinated individuals and recipients of PEGylated mRNA-LNP vaccines (Comirnaty and Spikevax), polysorbate-containing vaccines, or vaccines lacking both PEG and polysorbates. Quantitative ELISA was used to characterize anti-PEG and anti-polysorbate IgM and IgG responses in 325 plasma samples, while an equilibrium titration method was applied to assess IgG binding to PEG molecules, micelles, and PEGylated liposomes with defined structural features in 36 plasma samples. Results: Vaccination with PEGylated mRNA-LNPs was associated with increased anti-PEG antibody levels and qualitative changes in antibody binding behavior. Anti-PEG IgG antibodies displayed progressively higher avidity toward larger and structurally more complex PEG-containing antigens, with the strongest binding observed for PEGylated liposomes. Notably, vaccinated individuals, particularly those who received Spikevax, showed increased end-group and backbone-specific avidity, as well as an enhanced ability of antibody paratopes to engage shorter PEG chains. In contrast, polysorbate-containing or PEG-free vaccines did not elicit comparable effects. Conclusions: These findings suggest that vaccination with PEGylated mRNA-LNPs is associated with the emergence of altered antibody populations with increased end-group reactivity and higher avidity toward PEG-directed immune responses, despite PEG being a synthetic, nonprotein polymer. Antibody binding to LNPs, accompanied by the emergence of high-avidity anti-PEG IgG seems to be consistent with an increased risk of adverse events, particularly following repeated vaccinations, including complement activation-related pseudoallergy (CARPA) and anaphylaxis. It may also contribute to altered immune protection against the vaccine target, underscoring the need for avidity-aware risk-benefit assessment of PEGylated therapeutics. Full article