Search Results (1,305)

Background: Non-typeable Haemophilus influenzae (NTHi) is a major cause of acute respiratory tract infections and chronic airway disease, despite its clinical importance, no licensed vaccine is available, largely due to the extensive genetic and antigenic diversity among circulating isolates. We previously identified conserved outer membrane proteins capable of inducing systemic protection against NTHi. Methods: In this study, we evaluated whether a multi-antigen protein vaccine composed of conserved NTHi antigens (P5 and P26) could protect against pulmonary infection. Transgenic mice expressing human transferrin and factor H were immunized via the intraperitoneal or intranasal route and challenged intranasally with a clinical NTHi isolate. Bacterial clearance, antigen-specific mucosal and systemic antibody responses, and recruitment of innate immune cells to the airways were assessed. Results: Both immunization routes significantly reduced bacterial loads compared with controls. Vaccination induced robust mucosal and systemic IgG and IgA responses and enhanced early recruitment of macrophages, monocytes, dendritic cells, and neutrophils to the airways. Intranasal immunization elicited strong mucosal antibody responses and was associated with improved local bacterial clearance. Conclusions: These findings demonstrate that multi-antigen vaccines targeting conserved NTHi proteins can elicit effective mucosal and systemic immunity and represent promising candidates for the prevention against NTHi respiratory infections. Full article

Biological E’s BEVAC^® is a recombinant DNA hepatitis B vaccine that has been used in India for more than a decade in routine early-life immunization and has recently been prequalified by the World Health Organization (WHO). This multicentre, single-blind, parallel-group, randomized phase IV trial, conducted at seven study sites in India, compared the immunogenicity and safety of BEVAC^® with a licensed comparator vaccine (GeneVac-B^®, Serum Institute of India Pvt. Ltd, Pune, India.) in healthy term neonates and infants. Participants received three 0.5 mL doses administered intramuscularly at birth (within 24 h), 6 weeks of age, and 14 weeks of age. The primary endpoint was seroprotection (anti-HBs IgG ≥10 mIU/mL) at 28 days after the third dose (Day 126), compared using a non-inferiority margin of −10%. Secondary endpoints included safety and tolerability outcomes through Day 126. A total of 468 neonates were randomized (234 per group), of whom 44% were female. At Day 126, seroprotection rates were 98.2% (95% CI: 95.39, 99.50) with BEVAC^® and 99.1% (95% CI: 96.78, 99.89) with the comparator; the between-group difference was −0.9% (95% CI: −3.09, 1.24), meeting the prespecified non-inferiority criterion. Solicited adverse events within 7 days after any dose occurred in 29.1% (95% CI: 23.3, 35.3) of BEVAC^® recipients and 35.0% (95% CI: 28.9, 41.5) of comparator recipients, most commonly pyrexia, injection-site pain, and swelling; all were mild-to-moderate. No serious adverse events were reported. BEVAC^® demonstrated non-inferior immunogenicity to the licensed comparator and a comparable safety profile. Full article

Introduction: Peanut oral immunotherapy (P-OIT) is an emerging treatment strategy for peanut allergy (PA). Although a standardized pharmaceutical product, Peanut (Arachis hypogaea) Allergen Powder-dnfp, has been approved in several countries, it is not universally available. In such contexts, real-world protocols using readily utilizable peanut products may represent an alternative approach. This study aimed to describe the feasibility, safety, and clinical outcomes of P-OIT using toasted peanuts in a real-world effort in a pediatric population. Methods: This single-center retrospective cohort study enrolled children who initiated P-OIT at our tertiary pediatric hospital Allergy Unit between April 2015 and December 2024. Demographic and clinical features, allergy test results, and information about P-OIT were recorded. Desensitization was defined as tolerance of 630 mg of peanut protein (PP). Results: Sixty patients (51.7% male; median age 8.2 years) were included. 22/60 (36.7%) achieved desensitization within a median time of 22.7 months. 21/60 (35%) were still undergoing P-OIT at a median tolerated dose of 100 mg of PP, and 17/60 (28.3%) discontinued treatment, most commonly due to loss to follow-up (44%). At least one adverse reaction occurred in 43/60 (71.7%) patients, predominantly mild and self-limiting (68.3% resolved spontaneously, 39.5% occurred at home). However, 11/60 (18.3%) showed anaphylaxis, and 3/60 (5%) received adrenaline. A reduction in Ara h 2 serum-specific IgE levels compared to the baseline was observed in patients completing escalation (p = 0.03). Conclusions: In this real-world single-center cohort, P-OIT using toasted peanuts was feasible in a subset of patients and was associated predominantly with mild adverse reactions, although systemic reactions were also recorded. Treatment discontinuation and adherence remain relevant challenges. These findings highlight the need for prospective, controlled studies to better define the role, safety profile, and patient selection criteria for food-based P-OIT protocols in settings where standardized products are not available. Full article

The immunoglobulins (IG) or antibodies and the T cell receptors (TR) are the antigen receptors of the adaptive immune responses (AIR) of jawed vertebrates (Gnathostomata). IMGT^®, the international ImMunoGeneTics information system^®, was created in 1989 by Marie-Paule Lefranc (Laboratoire d’ImmunoGénétique Moléculaire (LIGM), Université de Montpellier and CNRS) to deal with and to manage the huge diversity of IG or antibodies and TR. The founding of IMGT^® marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics. For the first time, the IG and TR variable (V), diversity (D), joining (J) and constant (C) genes were officially recognized as ‘genes’, as were the conventional genes. The IMGT-ONTOLOGY CLASSIFICATION axiom and the concepts of classification have generated the IMGT nomenclature and the IMGT Scientific chart rules for assigning IMGT names to IG and TR genes and alleles of Homo sapiens and of any other jawed vertebrate species. The IMGT nomenclature is used for genes in locus, in sequences (genomic or rearranged, expressed or not) and in structures enabling comparative immunology, evolutionary immunogenetics, standardized analysis and comparison of IG and TR repertoires analysis in normal or pathologic situations. IMGT nomenclature is used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma), and in therapeutic antibody design, engineering and humanization. By providing consistent and high standard biocuration for the description of the IG and TR loci, genes and alleles, and for the analysis of the IG or antibody and TR-expressed rearranged sequences and proteins and structures, the IMGT nomenclature is the common language for immunoinformatics and artificial intelligence (AI). Full article

Bi-doped rare-earth iron garnet (Bi:RIG) single crystals are the core of optical isolators, and demand for them is surging due to the development of artificial intelligence (AI) technology. In this work, bismuth-doped terbium iron garnet (Bi:TbIG) single crystals with a composition of Bi_0.86Tb_2.14Fe₅O₁₂ and a size of 37 mm were successfully grown by the top-seeded solution growth (TSSG) method using a lead-containing flux system. These crystals exhibited a regular rhombic dodecahedron morphology enclosed by the {110} plane, and a growth rate of 0.018 mm/h perpendicular to the {110} planes. Systematic characterizations revealed that the crystals exhibited good compositional homogeneity, with no obvious Fe, Tb and Bi segregation from center to edge. Rocking curve tests presented a full width at half maximum of 172 arcsec. X-ray photoelectron spectroscopy (XPS) results demonstrated that Fe exists exclusively in the +3 valence state without detectable Fe²⁺, whereas Tb is present in the +4 valence state. In addition, O was lattice O²⁻, without obvious defects. Magneto-optical tests indicated that the uncoated TSSG-grown Bi:TbIG crystals had 71% transmittance in the 1200~1600 nm waveband, and a Faraday rotation coefficient of 0.132°/μm at 1310 nm. The 11 × 11 mm samples exhibited an extinction ratio stably above 40 dB. The 349 μm thick samples meet the application requirements of miniaturized optical isolators. This study verifies the feasibility of TSSG for growing Bi:TbIG single crystals, offering a new technical route for Bi:TbIG growth with potential value for practical application. Full article

Background: Interactive learning resources developed with the H5P platform have been progressively adopted to support autonomous learning and conceptual consolidation. However, empirical evidence regarding their impact on academic performance in theoretically demanding university courses remains limited. The primary aim of this study was to examine the effect of the structured integration of an interactive digital pedagogical resource developed with multiple-choice H5P on the academic performance of higher education students enrolled in a Motor Control course. Methods: A quasi-experimental study was conducted to compare two independent groups: a control group (CG; n = 90) and an intervention group (IG; n = 115), which had access throughout the semester to a multiple-choice interactive resource developed using the H5P platform. Academic performance was operationalized as the score obtained on a written summative assessment. Baseline equivalence between groups was assessed using an initial diagnostic test. Between-group comparisons were performed using robust non-parametric statistical procedures and further examined using a linear regression model adjusted for relevant covariates. Results: No statistically significant differences were found between groups in the baseline diagnostic test (p > 0.05), indicating comparable starting levels. At the end of the intervention period (≈2 months), the intervention group obtained significantly higher scores in the summative assessment (p < 0.001), with a large effect size (d = 0.87). Conclusions: The findings suggest that the structured integration of multiple-choice H5P resources may positively contribute to academic performance when used as a complementary tool alongside traditional teaching. These results reinforce the pedagogical potential of multiple-choice H5P to support autonomous learning and conceptual consolidation, while also highlighting the need for future research employing more rigorous experimental designs and process-based measures to better understand the underlying learning mechanisms. Full article

Avian influenza infections cause substantial economic losses in the poultry industry and raise public health concerns due to viral adaptation and cross-species transmission. The frequent antigenic drift of influenza viruses further complicates the prevention and treatment of avian respiratory infections. In this study, we generated high-affinity heavy-chain variable domain (VHH) nanobodies from naïve alpaca/camelid VHH libraries using phage display combined with H9N2 influenza A virus (IAV)-infected Madin-Darby Canine Kidney (MDCK) cells. Based on binding affinity and neutralization potential, we identified seven hemagglutinin (HA)-specific and two neuraminidase (NA)-specific VHHs. Molecular docking predicted the interaction sites of HA-specific VHHs (L1-2, L1-4, A5) and NA-specific VHHs (L1-3, L2-2), providing mechanistic insights. Notably, the three HA-specific VHHs (L1-2, L1-4, A5) showed cross-reactivity to representative HA subtypes (H1, H3, and influenza B), indicating recognition of conserved epitopes across divergent influenza strains. For the first time, these camelid nanobodies were fused to the chicken IgY Fc domain, and the expression cassette was integrated into the Saccharomyces cerevisiae genome, achieving a secretion yield of 15–20 mg/L of VHH-Fc antibodies. Experimental validation confirmed that the three HA-specific VHHs-Fc constructs effectively blocked viral infection, while the two NA-specific VHH-Fc constructs (L1-3, L2-2) inhibited NA activity, demonstrating the functional efficacy of the yeast-secreted VHH–IgY Fc platform. This novel IgY Fc fusion approach offers a scalable platform with enhanced stability, extended circulation potential, and applicability in poultry. Full article

Background: Mycoplasma pneumoniae (MP) is a major cause of respiratory tract infections in children and adolescents. Currently, there is no licensed vaccine, underscoring the urgent need for the development of safe and effective vaccines. Objective: The aim of this study is to develop a recombinant subunit vaccine candidate incorporating three antigens: the P1 protein, the P40/90 complex, and a detoxified mutant of community-acquired respiratory distress syndrome toxin. The protective efficacy of this vaccine candidate was also evaluated. Methods: Target genes were codon-optimized for expression in E. coli, and the recombinant proteins were successfully expressed and purified. The low-toxicity CARDS toxin mutant was screened based on TNF-α secretion levels in stimulated RAW264.7 cells. A three-component vaccine composed of P1, P40/90, and the mutant CARDS toxin was formulated and adjuvanted with either Al(OH)₃ alone or in combination with CpG. Mice were immunized, and immunogenicity was assessed by measuring antigen-specific IgG antibody titers. Protective efficacy was evaluated following challenge by analyzing lung histopathology, bacterial load, and inflammatory cytokine levels. Results: Seven high-purity recombinant proteins were successfully produced, including P1, the P40/90 complex, wild-type CARDS toxin, and four CARDS toxin mutants (E132A, E132Q, H36A, R10A). The E132A mutant was selected due to its significantly reduced toxicity while retaining immunogenicity. The three-component vaccine effectively elicited antibody responses against each of the included antigens. After three immunizations, IgG antibody titers in all groups reached approximately 10⁴. Immunized mice showed markedly reduced pulmonary pathology scores (control group: 2 or 2.67; immunized groups: 1.67, 1.33, and 0) and significantly decreased bacterial loads in lung tissue (control: 30.11 ± 10.40 cp/μL; immunized groups: 20.72 ± 4.37 cp/μL and 8.51 ± 8.32 cp/μL). Furthermore, the group receiving the alum + CpG adjuvant exhibited approximately a 10-fold higher antibody response compared with the alum-only group, indicating enhanced protective efficacy. Conclusions: The three-component candidate vaccine, MPtriV, adjuvanted with Al(OH)₃ + CpG, demonstrates promising immunogenicity, safety, and protective efficacy against Mycoplasma pneumoniae infection, providing a viable strategy and experimental foundation for the development of MP subunit vaccines. Full article

Fish allergy, mainly caused by Parvalbumin (PV), is a worldwide health issue with few effective mitigation options. This study investigated Maillard conjugation using chitosan (CS) and various saccharides to modify the structural, functional, and allergenic properties of turbot (Scophthalmus maximus) PV. Structural analyses, including SDS-PAGE, Western blotting, FTIR spectroscopy, and Circular dichroism, confirmed successful conjugation and significant changes in secondary structure, including decreases in α-helical content and increases in β-sheet and random-coil fractions. Glycation significantly boosted antioxidant activity, with total phenolic content (TPC) increasing up to 10.3 times and DPPH radical scavenging reaching 74.5% in the CS–xylose–PV conjugate (CXTPV). Indirect ELISA revealed notable (p < 0.05), sugar-dependent reductions in IgE-binding capacity, with reductions of up to approximately 72% for CXTPV. RBL-2H3 cell assays showed decreased β-hexosaminidase release (about 75% reduction), lowered IL-6 secretion, and strong inhibition of IL-4 production, indicating reduced allergenic potential and immune regulation. CXTPV demonstrated the best overall performance. These findings suggest that CS–saccharide Maillard conjugation is an effective approach for creating hypoallergenic marine ingredients with improved bioactive properties. Full article

Hypersensitivity reactions to iodinated contrast media (ICM) are traditionally categorized as immediate or delayed reactions, involving IgE-mediated pathways, non–IgE-dependent mast cell or complement activation, or T cell–mediated immune mechanisms. However, we observed that some individuals develop systemic inflammatory responses that do not fit these established categories. We describe here a case series of three patients who developed cytokine release syndrome (CRS)-like reactions following iodinated contrast administration, which were initially difficult to distinguish from sepsis and were only recognized after recurrent episodes. Clinical presentation, laboratory findings, cytokine profiles, allergy investigations, and treatment outcomes were reviewed. All patients developed fever, rigors, and hypotension within 5 to 70 h after exposure, accompanied by leukocytosis and markedly elevated inflammatory markers despite negative microbiological investigations. Serum tryptase levels remained within the normal range with no significant rise, while cytokine analyses demonstrated elevations of pro-inflammatory interleukin-6 and other cytokines in patients 1 and 3 where samples were available. Standard corticosteroid premedication did not prevent recurrence, and one patient developed systemic symptoms following intradermal testing. All patients improved with high-dose systemic corticosteroids and supportive care. These findings suggest that ICM may induce a cytokine-mediated inflammatory phenotype distinct from classical hypersensitivity reactions, highlighting the importance of early clinical recognition to guide diagnosis and management. Full article

Background: Rabies is a highly fatal zoonotic disease that causes approximately 59,000 human deaths worldwide each year. Current inactivated rabies vaccines require multiple doses and are associated with high costs. The full-length rabies virus glycoprotein (RVG), a membrane protein, exhibits substantial instability in its trimeric structure during recombinant expression. This instability makes it difficult to obtain high-purity, correctly folded antigens. Objectives: This study focuses on the preparation of a full-length recombinant RVG subunit vaccine candidate expressed in a glycoengineered Pichia pastoris system with mammalian-like glycosylation. Methods: The full-length RVG gene (including the transmembrane domain and cytoplasmic tail) from the Challenge Virus Standard-11 (CVS-11) strain was codon-optimized and inserted into the pPICZαA vector to construct the recombinant expression plasmid pPICZαA-RVG. The plasmid was transformed into glycoengineered Pichia pastoris X33-7 (low-mannose type) by electroporation for inducible expression. The target protein was purified by nickel affinity chromatography, anion-exchange chromatography, and Superdex-200 size-exclusion chromatography. The structural characteristics of the purified protein were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The purified antigen was formulated with the adjuvants AS03 or MF59. BALB/c mice (n = 5 per group) were immunized intramuscularly following a four-dose schedule (days 0, 7, 14, and 28). Antigen-specific IgG antibody titers were measured by ELISA, and neutralizing antibody titers were determined using the rapid fluorescent focus inhibition test (RFFIT). Results: Glycoengineered Pichia pastoris yeast strains expressing wild-type RVG (RVG-WT) or a mutant variant (RVG-M6: R84S, R199S, H270P, R279S, K300S, and R463S) were successfully constructed. The purified RVG antigen formed nanoparticles with an average particle size of approximately 75 nm. Immunized mice generated robust RVG-specific IgG responses, with titers reaching approximately 6.31 × 10⁵ for RVG-WT after the fourth immunization, compared to 3.16 × 10³ for RVG-M6 and 5.62 × 10³ for the RVG-WT-PEG control. Two weeks after the fourth immunization, RVG-WT formulated with AS03 or MF59 induced significant neutralizing antibody responses compared with the control group (p < 0.0001 and p < 0.01, respectively). The neutralizing antibody titers reached 1:79.43 in the AS03 group and 1:33.11 in the MF59 group, whereas the WT-PEG + AS03 control group showed a low titer of 1:3.72. In contrast, RVG-M6 formulated with MF59 failed to induce detectable neutralizing antibodies (1:3.02). Furthermore, RVG-WT + AS03 induced significantly higher neutralizing antibody responses than the WT-PEG + AS03 control group (p < 0.0001), and a significant difference was also observed between the RVG-WT + MF59 and RVG-M6 + MF59 groups (p < 0.01). Conclusions: The glycoengineered Pichia pastoris expression system successfully produced uniform full-length rabies virus glycoprotein nanoparticles with high purity. When formulated with the AS03 adjuvant, RVG-WT induced high-titer neutralizing antibodies in mice, suggesting a promising strategy for the development of recombinant subunit vaccines against rabies. However, this study is limited by the absence of challenge studies and validation in target animal species, which will be further investigated in future work. Full article

Erythropoietin-producing hepatocellular receptor A2 (EphA2) has emerged as a key mediator that promotes tumor malignant progression. EphA2 overexpression and its non-canonical signaling lead to oncogenic transformation, metabolic reprogramming, resistance to treatments, and metastasis. Therefore, strategies targeting EphA2 have been evaluated in clinical trials. However, the clinical effects were not sufficient. An anti-EphA2 monoclonal antibody (mAb), Ea₂Mab-7 (mouse IgG₁, κ), demonstrated high affinity and specificity among Eph receptors. In this study, we produced recombinant class-switched Ea₂Mab-7 variants, including Ea₂Mab-7-mG_2a (mouse IgG_2a) and Ea₂Mab-7-hG₁ (human IgG₁). Both Ea₂Mab-7-mG_2a and Ea₂Mab-7-hG₁ recognized human triple-negative breast cancer MDA-MB-231, pancreatic cancer MIA PaCa-2, and colorectal cancer HCT-15 in flow cytometry. Furthermore, both Ea₂Mab-7-mG_2a and Ea₂Mab-7-hG₁ exerted significant antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against these tumors. In mouse xenograft models of breast, pancreatic, and colorectal cancers, both mAbs demonstrated antitumor activity. These results indicate the potential of Ea₂Mab-7 variants for the treatment of EphA2-positive cancers. Full article

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with a high fatality rate, and no licensed vaccines are currently available. The nucleoprotein (NP) of the Crimean-Congo hemorrhagic fever virus (CCHFV) plays a critical role in viral replication and immune recognition, making it a promising target for vaccine development. This study aimed to design and evaluate a multiepitope recombinant DNA vaccine targeting the NP of CCHFV. Methods: Cytotoxic T lymphocyte (CTL) epitopes from the NP were predicted via immunoinformatics approaches and systematically assessed for antigenicity, allergenicity, toxicity, hydrophobicity, and global population coverage. The selected epitopes were incorporated into four DNA vaccine constructs driven by a cytomegalovirus promoter, adjuvanted with human β-defensin 3 (hBD3), and fused to the reporter protein mRuby3. The constructs were evaluated in vitro using a fluorescent reporter system designed to provide a readout of TCR signaling upon the co-culture of T lymphocytes with differentiated monocytic cells expressing antigens. In vivo immunogenicity and protective efficacy were assessed in BALB/c (exploratory pilot) and IFNAR^−/− mice, a highly susceptible model for viral infection. Cytokine responses were measured to assess immunogenicity. Results: In vitro assays showed predominantly antigen-independent T-cell activation, suggesting that nonspecific stimulation inherent to the reporter co-culture system likely obscured the detection of antigen-specific TCR signaling. In vivo analyses in BALB/c mice revealed that the constructs elicited only modest systemic cytokine profiles while CCHFV-specific IgG and IFN-γ secretion remained undetectable, indicating that antigen-specific T-cell and antibody responses were limited. In the IFNAR^−/− challenge model, several peptide groups achieved significant 2–3 log reductions in tissue viral RNA and infectious titers (p < 0.05 vs. sham). However, the observed viral modulations were insufficient to reach the protective threshold and did not translate to a survival benefit (0%). Conclusion: Despite a rational in silico foundation, the multiepitope DNA vaccine constructs demonstrated limitations in inducing potent, antigen-specific immunity across both mouse models. The lack of antigen-specific responses indicates limitations in epitope selection, construct design, and delivery strategies, requiring optimization of next-generation epitope-based vaccines. These findings highlight the complexity of translating computational epitope predictions into functional vaccines, and provide benchmark data as a framework to guide future optimizations. Full article

Background/Objectives: Helicobacter pylori (H. pylori) infection remains common globally, yet data on its prevalence and correlates among dental students in Eastern Europe are limited. Dental students may face potential occupational exposure through contact with saliva and aerosols during their clinical training. This study aimed to measure the seroprevalence of H. pylori among Lithuanian dental students and evaluate its associations with academic year, self-perceived oral health and hygiene factors, and gastrointestinal symptoms. Methods: An observational–analytical cross-sectional study was conducted in 2025 among 202 dental students from lower (I–II) and higher (IV–V) academic years at the Lithuanian University of Health Sciences. Participants underwent serological testing for H. pylori IgG antibodies using capillary blood and completed a structured questionnaire on sociodemographic factors, oral health behaviors, clinical exposure, and gastrointestinal symptoms assessed by the Gastrointestinal Symptoms Rating Scale (GSRS). Descriptive and bivariate statistical analyses were performed to assess associations. Results: Overall H. pylori seroprevalence was 12.4% and did not differ significantly in different academic years. Seropositivity was significantly associated with longer toothbrushing duration and a family history of stomach ulcer. No significant associations were found with the number of patients treated, the use of personal protective equipment, or most oral hygiene indicators. Higher-year students reported greater overall gastrointestinal symptom scores than lower-year students; however, GSRS scores did not differ between H. pylori-seropositive and -seronegative participants. Conclusions: H. pylori seroprevalence in this student population was relatively low, and no association was found with clinical exposure or gastrointestinal symptom severity. Household-related factors may be more relevant to transmission than occupational exposure in dental training. Further longitudinal studies are needed to clarify risk factors and transmission pathways. Full article

Gut ischemia/reperfusion (I/R) injury releases damage-associated molecular patterns (DAMPs), such as extracellular cold-inducible RNA-binding protein (eCIRP). Milk fat globule–epidermal growth factor VIII-derived oligopeptide 3 (MOP3) is a novel peptide enabling macrophage uptake of eCIRP via αvβ3-integrin. MOP3 reduces inflammation in gut I/R, but its mechanisms are not completely understood. We hypothesized MOP3 promotes macrophage polarization toward an anti-inflammatory, M2-like phenotype in gut I/R. We induced gut I/R in mice through 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Intestines were evaluated for macrophage polarization by flow cytometry and immunofluorescence histology. Peritoneal cavity macrophages were isolated from mice and treated with eCIRP, MOP3, α_vβ₃-antibody, and/or naïve IgG for 4 or 24 h. Polarity was assessed by flow cytometry, qPCR, and ELISA. Compared to the sham, the M2 proportion after gut I/R decreased by 22.7%, and the M1 proportion increased by 241%. MOP3 treatment increased the M2 proportion by 64.3%, and the M1 proportion decreased by 22.7%. In eCIRP-stimulated macrophages, MOP3 treatment increased M2-like and reduced M1-like cell-surface markers, gene expression, and cytokine levels. α_vβ₃ antibody dramatically reduced MOP3′s effects. MOP3 promotes M2 polarization through α_vβ₃ integrin-mediated clearance of eCIRP, a novel mechanism whereby MOP3 reduces gut I/R injury. Full article