Frontiers in Immunology最新文献

{"title":"Successful treatment of an elderly patient with lung squamous cell carcinoma by tislelizumab and chemotherapy: a case report with novel imaging findings.","authors":"Lufan Xu, Xinxin Ma, Yang Yang, Zhiqiang Ding, Yi Luo","doi":"10.3389/fimmu.2025.1543114","DOIUrl":"10.3389/fimmu.2025.1543114","url":null,"abstract":"<p><p>The advent of immunotherapy has transformed the therapeutic landscape for inoperable, locally advanced Non-Small cell lung cancer (NSCLC), particularly for lung squamous cell carcinoma (LUSC) with a predominance of negative driver genes. Based on the results of clinical trials such as KEYNOTE-042 and KEYNOTE-407, PD-1/PD-L1 inhibitors are now recognized as the standard of care for first-line or second-line treatment in many countries. Among the 17 immune checkpoint inhibitors sanctioned in China, tislelizumab, a domestically developed PD-1 inhibitor, enjoys broad application. Here, we present a case of a patient with LUSC who attained complete remission by cyst formation with the combination of tislelizumab and chemotherapy. Despite the absence of expression data for this patient, imaging studies revealed a reduction in the primary lesion size and the emergence of an uncommon cystic alteration post-treatment with sequential immunochemotherapy and tislelizumab monotherapy. As per the most recent follow-up, the lesion has vanished entirely. This outcome holds significant implications for the treatment of driver gene-negative LUSC by tislelizumab.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1543114"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive multiomics analysis identifies PYCARD as a key pyroptosis-related gene in osteoarthritis synovial macrophages.","authors":"Zihao Yao, Yuexin Li, Hanwen Mai, Zhuolun Wang, Haiyan Zhang, Daozhang Cai, Xiangjiang Wang","doi":"10.3389/fimmu.2025.1558139","DOIUrl":"10.3389/fimmu.2025.1558139","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a chronic joint disease that significantly impairs quality of life. Synovitis plays a pivotal role in OA progression, and pyroptosis, a form of programmed cell death associated with innate immune inflammation, may contribute to the pathogenesis of OA synovitis. Nevertheless, the precise role of pyroptosis in OA pathogenesis remains poorly understood.</p><p><strong>Methods: </strong>We performed an analysis of bulk RNA sequencing data to examine the expression profiles of pyroptosis-related genes in the OA synovium. A LASSO-Cox regression model was employed to identify pivotal genes. Single-cell RNA sequencing data were used to validate the expression of these genes in specific synovial cell clusters. Differentially expressed genes (DEGs) in macrophages with high or low expression levels of core genes were subjected to enrichment analysis. A protein-protein interaction (PPI) network was constructed to identify hub genes, and potential therapeutic compounds were predicted. Consensus clustering analysis was performed to examine the correlations between hub genes and disease status. After identifying PYCARD as the core pyroptosis gene in OA macrophages, we assessed the expression levels of PYCARD in the OA synovium and validated the expression of PYCARD and its related core genes in M1 macrophages.</p><p><strong>Results: </strong>A total of twenty pyroptosis-related DEGs were identified, and six core genes were selected through LASSO regression. PYCARD was identified as the key pyroptosis gene in macrophages. Furthermore, 57 therapeutic compounds targeting these genes were predicted. Validation confirmed the upregulation of PYCARD in the OA synovium and M1 macrophages.</p><p><strong>Conclusion: </strong>PYCARD was identified as the core pyroptosis gene in OA macrophages, and 57 potential therapeutic compounds were identified. This study offers valuable insights into potential treatment targets for OA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1558139"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA modification: a promising code to unravel the puzzle of autoimmune diseases and CD4⁺ T cell differentiation.","authors":"Hui Yu, Zhanchuan Ma, Sensen Su, Zheng Xu, Huanfa Yi","doi":"10.3389/fimmu.2025.1563150","DOIUrl":"10.3389/fimmu.2025.1563150","url":null,"abstract":"<p><p>Dynamic changes in various forms of RNA modification are critical to the functional homeostasis of the immune system and the pathophysiology of autoimmune diseases. RNA modification-related proteins play an essential role in these processes. At present, the research methods of RNA modification in autoimmune diseases are mainly to detect the expression changes of RNA modification-related proteins in tissues or cells, but there is a lack of explorations of target RNAs and in-depth mechanisms. Considering the important role of CD4⁺ T cell dysfunction in the pathogenesis and progression of autoimmune diseases, the regulatory effect of abnormal RNA modification on CD4⁺ T cells deserves attention, which will provide a perspective for further exploring the mechanism of RNA modification in autoimmune diseases. In this Review, we discuss the abnormal RNA modification changes in patients with autoimmune diseases and highlight the effects of these abnormal changes on CD4⁺ T cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563150"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics analysis and biological experiments to identify key immune genes in vascular dementia.","authors":"Yilong Zhao, Wen Xing, Weiqi Chen, Yilong Wang","doi":"10.3389/fimmu.2025.1560438","DOIUrl":"10.3389/fimmu.2025.1560438","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify key immune genes to provide new perspectives on the mechanisms and diagnosis of vascular dementia (VaD) based on bioinformatic methods combined with biological experiments in mice.</p><p><strong>Methods: </strong>We obtained gene expression profiles from a Gene Expression Omnibus database (GSE186798). The gene expression data were analysed using integrated bioinformatics and machine learning techniques to pinpoint potential key immune-related genes for diagnosing VaD. Moreover, the diagnostic accuracy was evaluated through receiver operating characteristic curve analysis. The microRNA, transcription factor (TF), and drug-regulating hub genes were predicted using the database. Immune cell infiltration has been studied to investigate the dysregulation of immune cells in patients with VaD. To evaluate cognitive impairment, mice with bilateral common carotid artery stenosis (BCAS) were subjected to behavioural tests 30 d after chronic cerebral hypoperfusion. The expression of hub genes in the BCAS mice was determined using a quantitative polymerase chain reaction(qPCR).</p><p><strong>Results: </strong>The results of gene set enrichment and gene set variation analyses indicated that immune-related pathways were upregulated in patients with VaD. A total of 1620 immune genes were included in the combined immune dataset, and 323 differentially expressed genes were examined using the GSE186798 dataset. Thirteen potential genes were identified using differential gene analysis. Protein-protein interaction network design and functional enrichment analysis were performed using the immune system as the main subject. To evaluate the diagnostic value, two potential core genes were selected using machine learning. Two putative hub genes, Rac family small GTPase 1(<i>RAC1</i>) and CKLF-like MARVEL transmembrane domain containing 5 (<i>CMTM5</i>) exhibit good diagnostic value. Their high confidence levels were confirmed by validating each biomarker using a different dataset. According to GeneMANIA, VaD pathophysiology is strongly associated with immune and inflammatory responses. The data were used to construct miRNA hub gene, TFs-hub gene, and drug-hub gene networks. Varying levels of immune cell dysregulation were also observed. In the animal experiments, a BCAS mouse model was employed to mimic VaD in humans, further confirmed using the Morris water maze test. The mRNA expression of <i>RAC1</i> and <i>CMTM5</i> was significantly reduced in the BCAS group, which was consistent with the results of the integrated bioinformatics analysis.</p><p><strong>Conclusions: </strong><i>RAC1</i> and <i>CMTM5</i> are differentially expressed in the frontal lobes of BCAS mice, suggesting their potential as biomarkers for diagnosing and prognosis of VaD. These findings pave the way for exploring novel molecular mechanisms aimed at preventing or treating VaD.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1560438"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyltransferase-like 3-mediated RNA N⁶-methyladenosine contributes to immune dysregulation: diagnostic biomarker and therapeutic target.","authors":"Deshuang Zhang, Ting Xu, Xiaoxue Gao, Yi Qu, Xiaojuan Su","doi":"10.3389/fimmu.2025.1523503","DOIUrl":"10.3389/fimmu.2025.1523503","url":null,"abstract":"<p><p>Methyltransferase-like 3 (METTL3) plays a crucial role in post-transcriptional gene regulation. Substantial evidence links METTL3 to various immune dysfunctions, such as the suppression of antiviral immunity during viral infections and the disruption of immune tolerance in conditions like autoimmune diseases, myeloid leukemia, skin cancers, and anticancer immunotherapy. However, a thorough review and analysis of this evidence is currently missing, which limits the understanding of METTL3's mechanisms and significance in immune dysfunctions. This review aims to elucidate the roles and mechanisms of METTL3 in these immune issues, highlighting its connections and proposing new insights into its modulation of immune responses. Analysis results in this review suggest that METTL3 hampers antiviral immunity, worsens viral replication and infection, and disrupts immune tolerance; conversely, regulating METTL3 enhances antiviral immunity and facilitates viral clearance. Moreover, clinical data corroborates these findings, showing that METTL3 overexpression is associated with increased susceptibility to viral infections and autoimmune conditions. This review establishes a theoretical basis for considering METTL3 as a novel regulator, an important diagnostic biomarker, and a potential target for treating immune dysfunctions.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1523503"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic functional assessment of T cells reveals an early suppression correlating with adverse outcome in polytraumatized patients.","authors":"Tobias Jooss, Katharina Maier, Lena-Marie Reichardt, Bianca Hindelang, Lönna Süberkrüb, Kim Lena Hamberger, Jasmin Maria Bülow, Konrad Schuetze, Florian Gebhard, Marco Mannes, Rebecca Halbgebauer, Lisa Wohlgemuth, Markus Huber-Lang, Borna Relja, Christian B Bergmann","doi":"10.3389/fimmu.2025.1538516","DOIUrl":"10.3389/fimmu.2025.1538516","url":null,"abstract":"<p><strong>Introduction: </strong>Most trauma patients require intensive care treatment and are susceptible to developing persistent inflammation and immunosuppression, potentially leading to multi organ dysfunction syndrome (MODS) and dependence on long term care facilities. T cells undergo changes in numbers and function post trauma. T cell dysfunction in polytraumatized patients was characterized using functional immunomonitoring to predict individual clinical outcome. Moreover, the potential to reverse T cell dysfunction using Interleukin (IL)-7 was examined.</p><p><strong>Methods: </strong>Blood samples were drawn from healthy individuals and prospectively enrolled polytrauma patients (Injury Severity Score ≥ 18) on admission, 8, 24 and 48 hours, 5 and 10 days after. CD3/28-stimulated cytokine production of T cells in whole blood was assessed via Enzyme Linked Immuno Spot (ELISpot). T cell subsets were quantified via counting and flow cytometry. Unfavorable physical performative outcome was defined as death or new functional disability necessitating long term care. Secondary outcomes were the development of MODS and in-hospital mortality. IL-7 was added ex vivo to test reversibility of cytokine disturbances.</p><p><strong>Results: </strong>34 patients were enrolled. The different outcome groups showed no difference in injury severity. Patients with favorable physical performative outcome revealed higher functional T cell specific Interferon γ (IFN-γ) and IL-17 (8 hours) and lower IL-10 production (day 5) and higher CD8 T cell concentrations. Patients without MODS development showed a higher IFN-γ (day 10), higher IL-2 (8 hours) and higher IL-17 production (admission, day 5). There were no differences regarding in-hospital mortality. Systemic blood IFN-γ, IL-2 and IL-10 concentrations only correlated with MODS (24 hours). Systemic CD8 T cell numbers correlated with functional IFN-γ production. Whole blood stimulation with IL-7 increased functional T cell IFN-γ release.</p><p><strong>Discussion: </strong>Our study reveals an early characteristic overall T cell dysfunction of pro-inflammatory (IFN-γ, IL-2, IL-17) and immunosuppressive (IL-10) subtypes in polytraumatized patients. Our data indicates that rather the functional capacity of T cells to release cytokines, but not systemic cytokine concentrations can be used to predict outcome post trauma. We assume that the early stimulation of pro- and anti-inflammatory T cells benefits polytraumatized patients. Potentiation of functional IFN-γ release might be achieved by IL-7 administration.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1538516"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microenvironments of tuberculous granuloma: advances and opportunities for therapy.","authors":"Gesa Krueger, Shah Faisal, Anca Dorhoi","doi":"10.3389/fimmu.2025.1575133","DOIUrl":"10.3389/fimmu.2025.1575133","url":null,"abstract":"<p><p>The hallmark tissue lesions of tuberculosis (TB) are granulomas. These multicellular structures exhibit varying degrees of cellular complexity, are dynamic, and show considerable diversity within and between hosts. Categorization based on gross pathologic features, particularly caseation and necrosis, was historically coined prior to the identification of mycobacteria as the causative agent of TB. More recently, granuloma zonation based on immune cell composition, metabolite abundance, and physical characteristics has gained attention. With the advent of single-cell analyses, distinct microenvironments and cellular ecosystems within TB granulomas have been identified. We summarize the architecture of TB granulomas and highlight their cellular heterogeneity, including cell niches as well as physical factors such as oxygen gradients that modulate lesion fate. We discuss opportunities for therapy, highlighting new models and the power of <i>in silico</i> modeling to unravel granuloma features and trajectories. Understanding the relevance of the granuloma microenvironment to disease pathophysiology will facilitate the development of more effective interventions, such as host-directed therapies for TB.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1575133"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of an inflammatory cytokine-based predictive model for the onset of prolonged postoperative ileus after radical gastrectomy: a prospective cohort study.","authors":"Chao Sui, BeiBei Wang, Yu Zhao, YunTian Guo, JinXin Zhu, Feng Yu, XiaoDong Zhou, XueFeng Bu, Jie Zhang","doi":"10.3389/fimmu.2025.1552944","DOIUrl":"10.3389/fimmu.2025.1552944","url":null,"abstract":"<p><strong>Background: </strong>Prolonged postoperative ileus (PPOI) is a common postoperative abdominal complication and is strongly associated with the inflammatory response. However, there is a lack of effective means to predict PPOI in patients with gastric cancer.</p><p><strong>Methods: </strong>222 patients underwent radical gastrectomy at our center were enrolled and divided into the training group and validation cohort. Receiver operating characteristic (ROC) curve analysis and univariate and multivariable logistic regression models were performed to help filter variables for inclusion in the predictive model. And then a nomogram for PPOI was established. The area under the ROC curve (AUC) was calculated to assess the prediction accuracy. Diagnostic calibration curves were used to assess the goodness-of-fit of the nomogram. Decision Curve Analysis (DCA) was applied to evaluate its clinical utility.</p><p><strong>Results: </strong>Significant increase of IL-6, IL-10, TNF-α, and CRP on the first postoperative day were found in PPOI patients after surgery. Univariate and multivariate analysis demonstrated that age ≥ 65, IL-6, and IL-10 were independent predictive factors for PPOI. We subsequently developed a prediction nomogram of PPOI which included age, IL-6, IL-10, and TNF-α. Further verification by the training and validation groups demonstrated the good predictive efficacy of our model, as well as favorable clinical benefits.</p><p><strong>Conclusions: </strong>We developed a novel and easy-to-use prediction nomogram for gastric cancer, which was primarily based on the postoperative level of inflammatory mediators. This model provided further clarification of the exact relationship between inflammatory factors and the occurrence of PPOI, and help us clinically identify the high-risk groups of PPOI for the purpose of early intervention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1552944"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-phenotype correlation in a cohort of pediatric patients with autoinflammatory diseases carrying <i>NOD2</i> variants.","authors":"Marco Francesco Natale, Camilla Celani, Silvia Federici, Chiara Passarelli, Chiara Perrone, Emiliano Marasco, Fabrizio De Benedetti, Antonella Insalaco","doi":"10.3389/fimmu.2025.1439333","DOIUrl":"10.3389/fimmu.2025.1439333","url":null,"abstract":"<p><strong>Background: </strong>Autoinflammatory diseases (AIDs) are a group of disease characterized by excessive activation of the innate immune system with episodes of spontaneous inflammation that can affect different organs. Many monogenic or acquired autoinflammatory diseases are described in literature. More recently the concept of disease with polygenic or complex inheritance has been introduced. Nucleotide binding oligomerization domain containing 2 (NOD2) gene variants are associated with Crohn's disease (CD), Blau syndrome and most recently with a polygenic autoinflammatory disease with onset in adult called NOD2-associated autoinflammatory disease (NAID).</p><p><strong>Objective: </strong>The aim of our study is to describe a pediatric cohort of patients with autoinflammatory disease carrying <i>NOD2</i> variants and to evaluate genotype-phenotype correlation.</p><p><strong>Methods: </strong>Twenty-five children with autoinflammatory disease and <i>NOD2</i> variants were enrolled in the study. Patients were divided into 3 groups based on the protein domain involved. Demographic and clinical features, imaging, laboratory exams and treatment were analyzed. The characteristics of our patients were compared with those of the adult cohort described by Yao in 2016-2018.</p><p><strong>Results: </strong>Fever was the main clinical characteristic of our children (68%) with long episodes and irregular pattern of recurrence. The disease typically affected skin (40%), joints (72%), bowel (60%) and lymphatic system (52%). Serositis and sensorineural deafness were less frequent. Excluding non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids were frequently used with satisfactory clinical response in the majority of patients. In patients with poor disease control or new flares after glucocorticoid tapering, non-biologic and biologic drugs were used with variable response. The comparison between the two most represented groups showed that patients with variants located on the NOD domain presented more homogeneous clinical characteristics with involvement of some target organs. Our patients were compared with the adult cohort described in literature with few differences.</p><p><strong>Conclusion: </strong>This is the first study to evaluate genotypic/phenotypic characteristics of children with systemic autoinflammatory disease and <i>NOD2</i> variants. The results, albeit preliminary and affected by the sample size, do not allow a definitive conclusion on a monogenic disease caused by mutation in <i>NOD2</i>, with the obvious exception of Blau syndrome. Variants in the NOD domain seem to be associated with a more homogenous clinical phenotype.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1439333"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory B cell proliferation drives differences in neutralising responses between ChAdOx1 and BNT162b2 SARS-CoV-2 vaccines.","authors":"David Hodgson, Yi Liu, Louise Carolan, Siddhartha Mahanty, Kanta Subbarao, Sheena G Sullivan, Annette Fox, Adam Kucharski","doi":"10.3389/fimmu.2025.1487066","DOIUrl":"10.3389/fimmu.2025.1487066","url":null,"abstract":"<p><strong>Introduction: </strong>Vaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals.</p><p><strong>Methods: </strong>Using in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type.</p><p><strong>Results: </strong>Our analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens.</p><p><strong>Discussion: </strong>Reconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1487066"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}