International immunology最新文献

{"title":"RNF213-TRAF2 interaction enhances inflammatory responses via NF-κB activation in moyamoya disease.","authors":"Mitsutaka Yasuda, Kaoru Murakami, Jing-Jing Jiang, Masaki Ito, Yuki Tanaka, Hiroki Tanaka, Rie Hasebe, Takeshi Yamasaki, Ari Hashimoto, Shimpei I Kubota, Shintaro Hojyo, Tatsuya Atsumi, Shigeru Hashimoto, Masaaki Murakami, Miki Fujimura","doi":"10.1093/intimm/dxag011","DOIUrl":"10.1093/intimm/dxag011","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a cerebrovascular disorder that predominantly affects East Asian populations. It is characterized by progressive stenosis or occlusion of terminal internal carotid arteries. Although inflammatory and autoimmune responses have been implicated in MMD pathogenesis, the precise molecular mechanisms underlying the disease remain poorly understood. RNF213, a key susceptibility gene for MMD, has been linked to inflammatory signaling; however, its role in NF-κB-driven inflammation remains unclear. Here, we identify RNF213 as a critical regulator of the IL-6 amplifier (IL6-Amp), a mechanism that enhances NF-κB-mediated inflammation in the presence of IL-6-STAT3 in non-immune cells. RNF213 knockdown reduced IL-6 expression in H4 cells, a model for IL6-Amp induction via tumor necrosis factor (TNF)-α and IL-6 co-stimulation, selectively suppressing NF-κB target genes. In vivo, RNF213 depletion attenuated inflammation in an NF-κB-dependent imiquimod-induced ear swelling model. The MMD-associated RNF213 p.R4810K variant enhanced NF-κB activation by strengthening the interaction between RNF213 and TRAF2, a key adaptor in TNF-α-NF-κB signaling. Consistent with these findings, histopathological analysis of superficial temporal arteries from MMD patients revealed genotype-dependent IL6-Amp activation, with pronounced phosphorylation of NF-κB p65 and STAT3 in homozygous carriers. In contrast, heterozygous and wild-type vessels showed minimal basal activation, but in vitro stimulation of arachnoid cells from a heterozygous patient recapitulated IL6-Amp responsiveness. Collectively, these findings establish RNF213 as a pivotal regulator of NF-κB-driven inflammation and suggest that the p.R4810K variant amplifies inflammatory signaling, thereby contributing to MMD pathogenesis. This study not only advances our understanding of MMD pathophysiology but also highlights potential therapeutic strategies targeting inflammation.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"494-505"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147528728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct fibrosis-associated macrophage subsets coordinate iron metabolism in pulmonary fibrosis.","authors":"Hiroshi Nabeshima, Kiyoharu Fukushima, Yu-Chen Liu, Daisuke Motooka, Takayuki Niitsu, Eriko Fukui, Michiko Ichii, Takuro Nii, Yuri Akamine, Nanako Hamada, Kazuki Hashimoto, Yuko Abe, Yasuharu Nagahama, Takanori Matsuki, Kazuyuki Tsujino, Keisuke Miki, James Badger Wing, Naoki Hosen, Yasushi Shintani, Atsushi Kumanogoh, Daisuke Okuzaki, Hiroshi Kida, Shizuo Akira","doi":"10.1093/intimm/dxag017","DOIUrl":"10.1093/intimm/dxag017","url":null,"abstract":"<p><p>Pulmonary fibrosis has a poor prognosis because of challenges in early diagnosis and therapeutic intervention. Current treatments remain largely ineffective due to an incomplete understanding of the complex pathology, including the interactions between fibroblasts and profibrotic immune cells within fibrotic lungs. To elucidate the dynamics of fibrosis, we performed single-cell RNA sequencing on bronchoalveolar lavage fluid obtained from patients with interstitial lung disease (ILD). We identified the SPP1- and APOE-expressing macrophage population that is commonly present across ILDs. Histological analysis showed that this macrophage population accumulated at the center of fibrotic foci. Furthermore, the ratio of this macrophage population was increased in both progressive pulmonary fibrosis and idiopathic pulmonary fibrosis. Transcriptomic analysis further divided this macrophage population into two subsets: SLC40A1⁺ or HAMP⁺ fibrosis-associated macrophages. We found that the relative balance of IL-10 and IL-8 regulated SLC40A1 and HAMP expression within fibrosis-associated macrophages. Additionally, histological analysis revealed that bronchial epithelium expressed IL-8, while type II alveolar epithelial cells expressed IL-10 in the fibrotic lung. SLC40A1⁺ fibrosis-associated macrophages localized to CD31⁺ perivascular regions and mediated the uptake and degradation of the hemoglobin-haptoglobin complex. This dual pathway-providing iron via SLC40A1 and intracellular iron accumulation via HAMP-facilitated the transition of fibroblasts into SPP1⁺ myofibroblasts. Moreover, ferroptotic fibroblasts secreted transforming growth factor-beta 1 (TGF-β1), which further contributes to fibrotic progression. In conclusion, aberrant iron metabolism orchestrated by fibrosis-associated macrophages may contribute to fibrosis by facilitating the transition of myofibroblasts. These findings provide mechanistic insight into the progression of autonomous pulmonary fibrosis.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"521-534"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple evolutionary routes to immune diversification across animals.","authors":"Mizuki Taguchi, Sébastien de La Forest Divonne, Ryo Morimoto","doi":"10.1093/intimm/dxag018","DOIUrl":"10.1093/intimm/dxag018","url":null,"abstract":"<p><p>Adaptive immunity is often viewed as a defining innovation of vertebrates, characterized by somatically diversified antigen receptors and clonal lymphocyte lineages. Yet the evolutionary origins of such systems remain incompletely understood. In this review, we examine adaptive immunity from a comparative perspective across Metazoa, focusing on the design principles that link molecular diversification, immune cell differentiation, and proliferative dynamics. We first outline the two adaptive immune architectures found in vertebrates. Jawed vertebrates employ immunoglobulin-based and T-cell receptor-based recognition generated through recombination-activating gene (RAG)-mediated V(D)J recombination, whereas jawless vertebrates assemble variable lymphocyte receptors using cytidine-deaminase-dependent diversification of leucine-rich repeat modules. Despite their distinct molecular entities, these systems converge on shared design principles, including somatic diversification, developmental restriction of genome editing, immune cell differentiation, and specialized microenvironments for immune education. To introduce evolutionarily more ancient systems, several diversification mechanisms of antigen receptors in invertebrates will be subsequently surveyed. These systems generate substantial molecular diversity without canonical clonal selection, suggesting that immune recognition and diversification can be achieved through multiple evolutionary strategies. Particular attention is given to emerging insights into invertebrate immune cell diversification, where single-cell transcriptomics is revealing complex hematopoietic lineages and regulatory programs. These observations suggest that adaptive immunity did not emerge abruptly but rather represents one solution within a broader evolutionary landscape of immune diversification strategies. Understanding how diversification, proliferation, and cellular organization interact across animal lineages will help clarify the fundamental design constraints that shaped the evolution of vertebrate adaptive immune systems.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"482-493"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELAVL1 modulates periodontal ligament fibroblast pyroptosis in periodontitis through the JAK2/STAT3/NLRP3 axis.","authors":"Huayong Zhan, Ge Shi, Qin Xie, Yanling Chen, Yuhua Zhang","doi":"10.1093/intimm/dxag014","DOIUrl":"10.1093/intimm/dxag014","url":null,"abstract":"<p><p>Periodontitis is an inflammatory disorder that leads to the destruction of periodontal tissues. Pyroptosis, related to the Nod-like receptor protein 3 (NLRP3) inflammasome, is implicated in the pathogenesis of periodontitis. ELAVL1 (embryonic lethal, abnormal vision, Drosophila-like 1), an N6-methyladenine (m6A) reader, is associated with inflammatory responses; however, its role in periodontitis requires further clarification. Our research elucidated the regulatory functions of ELAVL1 in periodontitis and explored the underlying mechanisms. Expression of ELAVL1 in periodontitis mice and Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced eriodontal ligament fibroblasts (PLFs) was assessed via quantitative real-time PCR (qRT-PCR) and western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to analyse IL-1β and IL-18 levels. The associated protein levels of the NLRP3 inflammasome, bone formation, and the JAK2/STAT3 (Janus kinase 2 / signal transducer and activator of transcription 3) pathway were detected using western blot. Pyroptosis was evaluated by flow cytometry. RNA immunoprecipitation (RIP), methylated RIP (MeRIP), and dual-luciferase reporter assay were performed to validate the association between ELAVL1 and JAK2 mRNA. Immunofluorescence was used to detect ELAVL1, NLRP3, and Vimentin expression in periodontal tissues. The pathological changes in periodontal tissues were determined by micro-CT and hematoxylin and eosin (H&E) staining. We found that ELAVL1 was upregulated in periodontitis tissues and P.g-LPS-stimulated PLFs. Mechanistically, ELAVL1 binds to JAK2 mRNA, enhancing its m6A modification and stability, thereby activating the JAK2/STAT3 signaling. Knockdown of ELAVL1 decreased NLRP3 inflammasome activation and pyroptosis in PLFs, inhibited inflammatory factor secretion, and inhibited activation of the JAK2/STAT3 pathway. However, these effects were partially reversed following treatment with C-A1. Furthermore, ELAVL1 knockdown attenuated alveolar bone loss, decreased p-JAK2 and p-STAT3 levels, and suppressed NLRP3-mediated pyroptosis in vivo. We conclude that ELAVL1 promotes periodontitis by mediating m6A modification of JAK2 and activating the JAK2/STAT3/NLRP3-mediated pyroptosis, suggesting its promise as a novel treatment target for periodontitis.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"506-520"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune responses underlying local and systemic adverse reactions to mRNA-lipid nanoparticle vaccines.","authors":"Tomohiro Takano, Takayuki Matsumura, Yoshimasa Takahashi","doi":"10.1093/intimm/dxag040","DOIUrl":"https://doi.org/10.1093/intimm/dxag040","url":null,"abstract":"<p><p>Vaccine reactogenicity refers to the capacity of a vaccine to induce transient local and systemic adverse reactions (ARs). Although these ARs are often attributed to vaccine-induced innate inflammation, accumulating evidence indicates that the inflammatory pathways causing symptoms are not necessarily identical to those required for protective immunity. mRNA-lipid nanoparticle (LNP) vaccines provide a valuable framework for examining this relationship, because both the mRNA cargo and the LNP delivery system can contribute to innate immune activation. Early inflammatory responses following mRNA-LNP vaccination appear to reflect the interplay of multiple signals, including ionizable lipid-driven signaling, mRNA-associated interferon (IFN) responses, endosomal membrane perturbation, and tissue-derived danger signals. These upstream events can be amplified through cytokine networks that promote systemic symptoms. Interleukin-1 (IL-1) has emerged as a major contributor to this process, although IL-6, tumor necrosis factor-alpha (TNF-α), type I IFN, and prostaglandin-related pathways also contribute, depending on the experimental model and context. In this review, we summarize recent evidence linking upstream sensing pathways to local and systemic ARs, and discuss how these pathways intersect with vaccine-induced adaptive immunity. We also consider booster-associated amplification of ARs as an example in which immune memory may reshape innate cytokine responses after repeated vaccination. Understanding these relationships will help delineate the shared and distinct inflammatory circuits underlying ARs and protective immunity. These mechanistic insights may also inform the rational design of low-reactogenic mRNA-LNP formulations that retain sufficient immunogenicity.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence and divergence of blood cell lineages in the history of animal evolution.","authors":"Yosuke Nagahata, Hiroshi Kawamoto","doi":"10.1093/intimm/dxag039","DOIUrl":"https://doi.org/10.1093/intimm/dxag039","url":null,"abstract":"<p><p>Humans possess various blood cell types, such as T cells, B cells, monocytes/macrophages, neutrophils, dendritic cells, erythrocytes, and platelets/thrombocytes, and these lineages are shared by nearly all vertebrates. Although invertebrates such as tunicates, sea urchins, flies, and sponges possess different blood cell lineages, some homology exists between vertebrate and invertebrate blood cells. Comparing cell lineages between different species can help estimate the evolution of blood cell lineages and immune systems across more than 600 million years of animal history. Studies on blood cells in vertebrate and invertebrate species have put some mile stones in the roads of blood cell evolution, but a comprehensive map has not been drawn. Recent advances in sequencing and bioinformatic technologies and the accumulation of genomic information for various animal species enabled us to develop an analytical method to compare cell lineages between far different species. Our recent work suggested one probable evolutionary history of blood cell lineages, in which T cells, NK cells, ILC, mast cells, erythrocytes, and thrombocytes evolved from prototypic mast cells. In addition, a vestige of this history was detected in our body as a linage restriction process in blood cell differentiation. Thus, studying evolution can help clarify current biological systems, and vice versa.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th1-Adapted Regulatory T Cells in Tumor Immunity and Inflammatory Diseases.","authors":"Ayumi Kuratani, Masaaki Okamoto, Takashi Kobayashi, Masahiro Yamamoto","doi":"10.1093/intimm/dxag038","DOIUrl":"https://doi.org/10.1093/intimm/dxag038","url":null,"abstract":"<p><p>Regulatory T cells (Tregs) play an essential role in maintaining immune tolerance and controlling excessive inflammation. Although traditionally viewed as a stable lineage dedicated to broad immunosuppression, accumulating evidence has revealed that Tregs exhibit remarkable heterogeneity and functional adaptability, allowing them to undergo specialization in response to local inflammatory environments. Among these specialized subsets, Th1-type Tregs (Th1-Tregs), characterized by the co-expression of Foxp3 and the transcription factor T-bet, have emerged as key regulators of type 1 immune responses. By expressing the chemokine receptor CXCR3, these cells localize to IFN-γ-rich inflammatory sites and selectively modulate Th1-driven immune circuits. Recent studies have demonstrated that Th1-Tregs play context-dependent roles across diverse pathological conditions. In the tumor microenvironment, they suppress cytotoxic immunity and contribute to tumor immune evasion. In contrast, during autoimmune diseases and acute infections, Th1-adapted regulatory programs protect host tissues by restraining excessive inflammation. These findings highlight how regulatory T cells dynamically adapt to local inflammatory environments to control type 1 immune responses in different tissues. In this review, we summarize the molecular mechanisms underlying Th1-Treg differentiation and discuss how these specialized regulatory programs shape immune responses across different disease contexts.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic CD4+ T cells across aging: a conceptual framework for health, protection, pathology, and age-associated diseases.","authors":"Tatsuya Hasegawa, Kosei Nishitani, Kenji Kabashima","doi":"10.1093/intimm/dxag037","DOIUrl":"https://doi.org/10.1093/intimm/dxag037","url":null,"abstract":"<p><p>Aging is the primary risk factor for a wide spectrum of chronic diseases, ranging from infectious diseases and cancer to autoimmunity and neurodegeneration. One of the key drivers of this increased susceptibility is the progressive decline in immune function-immunosenescence that reshapes the host's inflammatory landscape. Emerging evidence points to an age-associated expansion of cytotoxic CD4+ T cells (CD4 CTLs), which can play context-dependent protective or pathogenic roles in host homeostasis and disease, reflecting their unique integration of helper and cytotoxic programs as well as their preferential expansion during aging. On the protective side, CD4 CTLs contribute to immune surveillance and host defense against viral infections and malignancies. Conversely, in selected settings, they can function as pathogenic effectors in autoimmune and neurodegenerative disorders. In this review, we synthesize the emerging biology of CD4 CTLs, highlighting their differentiation and dual roles in protection and pathology. Beyond a descriptive overview, we propose a conceptual framework that places age-associated CD4 CTL expansion at the intersection of aging and age-associated disease. Rather than viewing late-life pathologies as fully independent events, we suggest that at least a subset may be partially interconnected by recurrent CD4 CTL programs, while emphasizing that the strength of evidence and the degree of causality differ substantially by disease context. This framework provides a basis for asking when CD4 CTLs should be enhanced, restrained, or more precisely redirected to promote healthy longevity.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CCL20-CCR6 axis predominantly drives IL-17-mediated psoriasis while modestly contributing to papain-induced type 2 inflammation.","authors":"Supanuch Ekronarongchai, Nozomi Sachi, Yomei Kagoshima, Tatsuhito Umeki, Shohei Terashi, Tipanan Khunsri, Sotaro Ozaka, Masaaki Okamoto, Masashi Ohtani, Sita Virakul, Kenji Kabashima, Tanapat Palaga, Naganori Kamiyama, Takashi Kobayashi","doi":"10.1093/intimm/dxag036","DOIUrl":"https://doi.org/10.1093/intimm/dxag036","url":null,"abstract":"<p><p>Chronic inflammatory skin diseases such as psoriasis and atopic dermatitis (AD) are characterized by immune dysregulation. The chemokine CCL20 and its unique receptor CCR6 are upregulated in lesional skin of patients with both psoriasis and AD. To investigate their roles in disease pathogenesis, CCL20- and CCR6-deficient (KO) mice were generated. In an imiquimod (IMQ)-induced psoriasis model, clinical scores were significantly reduced in both CCL20- and CCR6-KO mice compared with wild-type (WT) mice. Moreover, the expression of Th17-related cytokines and the migration of γδlow+ T cells into the epidermis were markedly decreased in IMQ-treated KO mice. In contrast, in a papain-induced AD model, KO mice exhibited an approximately 40% reduction in disease severity compared with WT controls. Papain-treated KO mice showed significant reductions in type 2-associated responses, including IL-4 production, IgE levels, and mast cell accumulation, whereas effects on other immune cell populations were limited. Collectively, these findings indicate that the CCL20-CCR6 axis predominantly drives psoriasis pathogenesis, whereas its contribution to papain-induced AD-like inflammation is comparatively limited. These results highlight the CCL20-CCR6 axis as a key regulator of IL-17-driven skin inflammation and a potential therapeutic target, particularly in psoriasis.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transiently produced IgGs enable infection-blocking vaccine efficacy assessment.","authors":"Jingzhi Li, Chaoyi Gu, Xiaochun Chen, Shuixing Sheng, Qinghong Xue, Hongwei Ma","doi":"10.1093/intimm/dxag035","DOIUrl":"https://doi.org/10.1093/intimm/dxag035","url":null,"abstract":"<p><p>Many vaccines are evaluated based on their ability to prevent symptoms, rather than infection itself, limiting their effectiveness in controlling asymptomatic transmission and achieving viral eradication. Here, we aimed to develop a serology-based strategy to detect asymptomatic infections and quantify the duration of infection-blocking protection, thereby enabling data-driven re-vaccination and offering a complementary framework for future infection-blocking VE evaluation. Using porcine circovirus 2 vaccines as a model, we identified that anti-peptide IgGs appear transiently after vaccination but are reproducibly re-induced upon post-vaccination infection, whereas anti-Capsid protein IgGs persist over time. This distinct serological response enables detection of new infections post-vaccination. By analyzing anti-peptide IgG response patterns across multiple sampling time points, we defined a digital microarray index (DMI) that captured the duration of vaccine-induced protection, and successfully ranked the infection-blocking efficacy of five commercial vaccines. Application to single-day samples from eight farms demonstrated that DMI, when paired with vaccination timing, accurately determined herd-level immune status and informed rational re-vaccination scheduling. This study introduces a serological platform for detecting asymptomatic infections and quantifying infection-blocking protection. The DMI enables high-resolution immune surveillance, informs timely re-vaccination, and lays the groundwork for future VE trials targeting infection-blocking and pathogen elimination.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}