Frontiers in Immunology最新文献

{"title":"Osteoporosis and fractures in systemic vasculitides: a systematic review and meta-analysis.","authors":"Angelo Fassio, Alvise Berti, Alessandro Mantovani, Giovanni Adami, Francesco Pollastri, Davide Gatti, Riccardo Bixio, Valeria Messina, Maurizio Rossini, Davide Bertelle, Eugenia Bertoldo, Isotta Galvagni, Roberto Bortolotti, Ombretta Viapiana","doi":"10.3389/fimmu.2025.1545546","DOIUrl":"10.3389/fimmu.2025.1545546","url":null,"abstract":"<p><strong>Background/aim: </strong>We performed a systematic review and meta-analysis of observational studies aimed at investigating the prevalence of osteoporosis and osteoporotic fractures in subjects affected by systemic vasculitides (SVs) as well as to explore their risk of osteoporosis and osteoporotic fractures when compared to healthy controls.</p><p><strong>Methods: </strong>Scopus, Web of Science and PubMed were systematically searched from inception to February 2024 for observational studies investigating the prevalence of osteoporosis and fragility fractures in adults with SVs. In addition, when available, we assessed the odd ratios (OR) of prevalent osteoporosis and fragility fractures amongst subjects with SVs vs. healthy controls. Data from eligible studies were extracted, and meta-analysis was performed using a random effects model to obtain ORs with 95% confidence intervals (CIs). Subgroup analyses and meta-regressions were also performed. This study was registered in Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/3G7RJ).</p><p><strong>Results: </strong>Forty studies with 23,358 individuals affected by SVs were included. The overall prevalence of osteoporosis and fragility fractures in the SV patients were respectively 14.64% (95%CI 12.21-18.89), and 17.08% (95%CI 11.42-24.78). The ORs for osteoporosis and fragility fractures in SV patients when compared with healthy controls were 2.92 (95%CI 1.72-4.98) and 2.39 (95%CI 1.34-4.26) respectively. The univariable meta-regression analysis showed a significant association between cumulative glucocorticoids' dosage (total grams) and risk of prevalent osteoporosis (estimate = 0.0995, R² = 0.24, p=0.0194).</p><p><strong>Conclusion: </strong>SVs are associated with an increased risk for osteoporosis and fragility fractures, suggesting that active vigilance and pre-emptive screening are recommended.</p><p><strong>Systematic review registration: </strong>https://archive.org/details/osf-registrations-3g7rj-v1.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1545546"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752092","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":"Editorial: The next stage of immune cell design: selective targeting of multi-antigen profiles.","authors":"Alexander Kamb, Jackson G Egen","doi":"10.3389/fimmu.2025.1585904","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1585904","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1585904"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752128","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":"Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria.","authors":"Wenwen Ding, Yiwen Cheng, Xia Liu, Zhangcheng Zhu, Lingbin Wu, Jie Gao, Wenhui Lei, Yating Li, Xin Zhou, Jian Wu, Yongtao Gao, Zongxin Ling, Ruilai Jiang","doi":"10.3389/fimmu.2025.1563450","DOIUrl":"10.3389/fimmu.2025.1563450","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic and antimicrobial therapies. The rise of multidrug-resistant bacteria has led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, and healthcare costs. Tackling this crisis requires the development of novel antimicrobial agents, optimization of current therapeutic strategies, and global initiatives in infection surveillance and control. Recent studies highlight the crucial role of the human gut microbiota in defending against AMR pathogens. A balanced microbiota protects the body through mechanisms such as colonization resistance, positioning it as a key ally in the fight against AMR. In contrast, gut dysbiosis disrupts this defense, thereby facilitating the persistence, colonization, and dissemination of resistant pathogens. This review will explore how gut microbiota influence drug-resistant bacterial infections, its involvement in various types of AMR-related infections, and the potential for novel microbiota-targeted therapies, such as fecal microbiota transplantation, prebiotics, probiotics, phage therapy. Elucidating the interactions between gut microbiota and AMR pathogens will provide critical insights for developing novel therapeutic strategies to prevent and treat AMR infections. While previous reviews have focused on the general impact of the microbiota on human health, this review will specifically look at the latest research on the interactions between the gut microbiota and the evolution and spread of AMR, highlighting potential therapeutic strategies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563450"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752038","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 multi-omics landscape of non-small cell lung cancer with distant metastasis.","authors":"Teng He, Ting Jiang, Xiaoyuan Sun, Fang Yang, Dan Zhang, Shan Yao, Jiangrong Liao, Xueling Wu","doi":"10.3389/fimmu.2025.1560724","DOIUrl":"10.3389/fimmu.2025.1560724","url":null,"abstract":"<p><strong>Background: </strong>Distant metastasis is one of the important factors affecting the prognosis of lung cancer patients. Extracellular vesicles (EVs) play an important role in the occurrence, development, and metastasis of cancer. However, it is currently unclear whether EVs in BALF are involved in distant tumor metastasis.</p><p><strong>Methods: </strong>we collected bronchoalveolar lavage fluid (BALF) from patients with metastatic and non-metastatic non-small cell lung cancer (NSCLC) to isolate exosomes, which were then characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), followed by comprehensive metabolomic and proteomic analysis to ultimately construct a distant metastasis prediction model for non-small cell lung cancer.</p><p><strong>Results: </strong>Our research has found that the BALF of NSCLC patients is rich in EVs, which have typical morphology and size. There are significant differences in protein expression and metabolite types between patients with distant metastasis and those without distant metastasis. Sphingolipid metabolism pathways may be a key factor influencing distant metastasis in NSCLC. Subsequently, we constructed a predictive model for distant metastasis in NSCLC based on differentially expressed proteins identified by proteomics. This model has been proven to have high predictive value.</p><p><strong>Conclusion: </strong>The multi-omic analysis generated in this study provided a global overview of the molecular changes, which may provide useful insight into the therapy and prognosis of NSCLC metastasis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1560724"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752260","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":"T-cell receptors identified by a personalized antigen-agnostic screening approach target shared neoantigen KRAS Q61H.","authors":"Volker Lennerz, Christoph Doppler, Martina Fatho, Anja Dröge, Sigrid Schaper, Kristin Gennermann, Nadine Genzel, Stephanie Plassmann, David Weismann, Samuel W Lukowski, Dominik Bents, Christina Beushausen, Karen Kriese, Hermann Herbst, Volkhard Seitz, Rudolf Hammer, Paul J Adam, Stephan Eggeling, Catherine Wölfel, Thomas Wölfel, Steffen Hennig","doi":"10.3389/fimmu.2025.1509855","DOIUrl":"10.3389/fimmu.2025.1509855","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT) with TCR-engineered T-cells represents a promising alternative to TIL- or CAR-T therapies for patients with advanced solid cancers. Currently, selection of therapeutic TCRs critically depends on knowing the target antigens, a condition excluding most patients from treatment. Direct antigen-agnostic identification of tumor-specific T-cell clonotypes and TCR-T manufacturing using their TCRs can advance ACT for patients with aggressive solid cancers. We present a method to identify tumor-specific clonotypes from surgical specimens by comparing TCRβ-chain repertoires of TILs and adjacent tissue-resident lymphocytes. In six out of seven NSCLC-patients analyzed, our selection of tumor-specific clonotypes based on TIL-abundance and high tumor-to-nontumor frequency ratios was confirmed by gene expression signatures determined by scRNA-Seq. In three patients, we demonstrated that predicted tumor-specific clonotypes reacted against autologous tumors. For one of these patients, we engineered TCR-T cells with four candidate tumor-specific TCRs that showed reactivity against the patient's tumor and HLA-matched NSCLC cell lines. The TCR-T cells were then used to screen for candidate neoantigens and aberrantly expressed antigens. Three TCRs recognized recurrent driver-mutation KRAS Q61H-peptide ILDTAG<b>H</b>EEY presented by HLA-A*01:01. The TCRs were also dominant in a tumor relapse, one was found in cell free DNA. The finding of homologous TCRs in independent KRAS Q61H-positive cancers suggests a therapeutic opportunity for HLA-matched patients with KRAS Q61H-expressing tumors.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1509855"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752150","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":"Miquelianin inhibits IAV infection via the MAPK signaling pathway both <i>in vitro and in vivo</i>.","authors":"He Li, Beilei Shen, Yan Bi, Yan Sun, Shijun Zhang, Kun Xue, Qiuyue Wang, Bingshuo Qian, Junkui Zhang, Lingjun Fan, Zhengyuan Fang, Tiecheng Wang, Yuwei Gao, Donghui Yue","doi":"10.3389/fimmu.2025.1532336","DOIUrl":"10.3389/fimmu.2025.1532336","url":null,"abstract":"<p><strong>Background: </strong>Influenza is an acute respiratory infectious disease primarily transmitted through airborne droplets. The prevalence and spread of influenza viruses have significant impacts on global economic development and public health. Current prevention and control strategies for influenza virus infections mainly rely on vaccines and antiviral drugs. However, vaccine efficacy is limited by the antigenic drift and mutation characteristics of influenza viruses, while antiviral drug resistance is increasingly prevalent. Therefore, there is an urgent need for the development of novel antiviral agents. Flavonoids, widely distributed in plants, possess various potent biological properties, including antioxidant, anti-inflammatory, antibacterial, and anticancer activities, which contribute to the management and prevention of numerous diseases. This study aims to investigate the <i>in vitro</i> and <i>in vivo</i> anti-influenza A virus activity of quercetin, taxifolin, and miquelianin, as well as their underlying.</p><p><strong>Methods: </strong><i>In vitro</i> infection model (MDCK cells) and mouse lethal infection model of Infuenza A virus were used to evaluate the antiviral activity of quercetin, taxifolin and miquelianin. Subsequently, we applied network pharmacology to elucidate the mechanism of action and validate the findings for miquelianin.</p><p><strong>Results: </strong>Miquelianin effectively inhibits the replication of H1N1-UI182 both <i>in vitro</i> and <i>in vivo</i> and provides protection against lethal H1N1-UI182 infection in mice. Compared to virus-infected controls, miquelianin reduces lung injury. Furthermore, by inhibiting the MAPK signaling pathway, miquelianin prevents the overproduction of cytokines, such as IL-6 and IL-1β, induced by viral infection, thereby alleviating inflammatory responses.</p><p><strong>Conclusion: </strong>Miquelianin is a monomer extracted from traditional Chinese medicine, exhibiting inhibitory effects on H1N1-UI182 replication and lung injury mitigation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1532336"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752301","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":"New progress in imaging diagnosis and immunotherapy of breast cancer.","authors":"Jie He, Nan Liu, Li Zhao","doi":"10.3389/fimmu.2025.1560257","DOIUrl":"10.3389/fimmu.2025.1560257","url":null,"abstract":"<p><p>Breast cancer (BC) is a predominant malignancy among women globally, with its etiology remaining largely elusive. Diagnosis primarily relies on invasive histopathological methods, which are often limited by sample representation and processing time. Consequently, non-invasive imaging techniques such as mammography, ultrasound, and Magnetic Resonance Imaging (MRI) are indispensable for BC screening, diagnosis, staging, and treatment monitoring. Recent advancements in imaging technologies and artificial intelligence-driven radiomics have enhanced precision medicine by enabling early detection, accurate molecular subtyping, and personalized therapeutic strategies. Despite reductions in mortality through traditional treatments, challenges like tumor heterogeneity and therapeutic resistance persist. Immunotherapies, particularly PD-1/PD-L1 inhibitors, have emerged as promising alternatives. This review explores recent developments in BC imaging diagnostics and immunotherapeutic approaches, aiming to inform clinical practices and optimize therapeutic outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1560257"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752053","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":"Measles-mumps-rubella-vaccination at 6 months of age induces measles-specific T cell responses: a randomized controlled trial.","authors":"Søren Buus, Dorthe Maria Vittrup, Jonas Damgård Schmidt, Andreas Jensen, Anette Stryhn, Lone Graff Stensballe","doi":"10.3389/fimmu.2025.1546253","DOIUrl":"10.3389/fimmu.2025.1546253","url":null,"abstract":"<p><strong>Background: </strong>Measles is a highly contagious viral disease, particularly severe in infants. Protection in early life is provided by maternally transferred antibodies, but this period is shorter in infants of previously vaccinated mothers (PVMs) compared to infants of previously measles-infected mothers (PIMs). Earlier measles-mumps-rubella (MMR) vaccination may compensate for this. To evaluate immune responses, 6-month-old infants were randomized to receive early MMR or placebo. This study reports the cellular immune outcomes and summarizes serological and T-cell responses.</p><p><strong>Methods: </strong>A double-blind, randomized trial involved 6540 Danish infants aged 5-7 months, eligible if birth weight exceeded 1000 grams and gestational age was ≥32 weeks. Participants were randomized 1:1 to receive M-M-RVaxPro or placebo. Blood samples were collected before intervention, four weeks after intervention, and four weeks after routine MMR at 15 months. Peripheral blood mononuclear cells (PBMCs) were prepared, and an IFN-γ specific ELISpot assay measured measles-specific T cells.</p><p><strong>Results: </strong>Among 750 infants (341 MMR, 409 placebo) in the cellular immunogenicity trial, a significant cellular immune response was observed one-month post-intervention in the MMR group compared to placebo (geometric mean ratio [GMR]: 12.3; 95% CI: 6.9-21.9). The cellular conversion rate (CCR) in the MMR group was 45%, comparable to the previously reported seroconversion rate. However, following routine MMR at 15 months, a reduced cellular response was observed in the early MMR group (GMR: 0.6; 95% CI: 0.3-0.9). Post-routine MMR, CCRs were 66% (MMR) and 74% (placebo). The immune conversion rate (ICR, defined as seroconversion and/or T-cell response) reached 99% in both groups post-routine MMR.</p><p><strong>Conclusion: </strong>Early MMR at 6 months elicited significant measles-specific cellular responses, though the CCR was lower than after routine MMR at 15 months. However, when combining serological and cellular responses, 99% of infants achieved immune conversion by 15 months. Early MMR could help reduce measles burden in infants in endemic settings without compromising subsequent immunizations.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov, identifier NCT03780179, EudraCT 2016-001901-18.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1546253"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752291","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":"Translation of bi-directional transcripts enhances MHC-I peptide diversity.","authors":"Filip Zavadil, Tomas Henek, Justine Habault, René Chemali, Maria Camila Tovar-Fernandez, Chrysoula Daskalogianni, Laurence Malbert-Colas, Lixiao Wang, Sivakumar Vadivel Gnanasundram, Borek Vojtesek, Lenka Hernychova, Sebastien Apcher, Robin Fahraeus","doi":"10.3389/fimmu.2025.1554561","DOIUrl":"10.3389/fimmu.2025.1554561","url":null,"abstract":"<p><p>Antisense transcripts play an important role in generating regulatory non-coding RNAs but whether these transcripts are also translated to generate functional peptides remains poorly understood. In this study, RNA sequencing and six-frame database generation were combined with mass spectrometry analysis of peptides isolated from polysomes to identify Nascent Pioneer Translation Products (Na-PTPs) originating from alternative reading frames of bi-directional transcripts. Two Na-PTP originating peptides derived from antisense strands stimulated CD8⁺ T cell proliferation when presented to peripheral blood mononuclear cells (PBMCs) from nine healthy donors. Importantly, an antigenic peptide derived from the reverse strand of two cDNA constructs was presented on MHC-I molecules and induced CD8⁺ T cell activation. The results demonstrate that three-frame translation of bi-directional transcripts generates antigenic peptide substrates for the immune system. This discovery holds significance for understanding the origin of self-discriminating peptide substrates for the major histocompatibility class I (MHC-I) pathway and for enhancing immune-based therapies against infected or transformed cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1554561"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752159","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":"Evaluation of dual pathogen recognition receptor agonists as adjuvants for respiratory syncytial virus - virus-like particles for pulmonary delivery.","authors":"Ahmedali S Mandviwala, Komal Liman, Anke L W Huckriede, Vidya A Arankalle, Harshad P Patil","doi":"10.3389/fimmu.2025.1561297","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1561297","url":null,"abstract":"<p><strong>Introduction: </strong>Respiratory syncytial virus (RSV) remains a significant global health concern, particularly for infants and young children in developing countries. Despite ongoing research efforts, an effective RSV vaccine has yet to be approved for widespread use. Use of two separate pattern recognition receptor (PRR) agonists as adjuvants in vaccine formulations has shown to enhance the immune response against the antigen. The limitation with the use of two adjuvants is that they need not necessarily bind to PRRs on the same cell. This study evaluates the efficacy of two different dual PRR binding chimeric molecules CL413 (TLR2/TLR7 agonist) and CL429 (TLR2/NOD2 agonist) as adjuvants for RSV virus-like particles (VLPs) delivered via the pulmonary route in mice for induction of mucosal and systemic immunity.</p><p><strong>Methods: </strong>BALB/c mice were immunized twice with the RSV-VLPs alone or adjuvanted with CL413, CL429, mixture of single PRR agonists Pam3CSK4+ L18-MDP or Pam3CSK4+ imiquimod via the pulmonary route. The mixture of single PRR agonists adjuvants was used as control for chimeric adjuvants. Immune responses were evaluated by measuring antibody levels in sera and respiratory tract; cytokine production, B and T cell responses in the lungs and spleen.</p><p><strong>Results: </strong>Pulmonary immunization with CL413-adjuvanted VLPs induced robust nasal IgA responses against the RSV F and G proteins, which was not observed for the other adjuvant combinations. CL413 also enhanced serum IgG levels and promoted a balanced Th1/Th2 response, as evidenced by IgG2a/IgG1 ratios. CL413 elicited strong pro-inflammatory responses in the lungs of mice, including elevated levels of IFN-γ, TNF-α, IL-6, and IL-17A. Flow cytometry analysis revealed increased numbers of tissue-resident class-switched B cells in the lungs of mice that were immunized with VLPs adjuvanted with CL413 and CL429. CD4+ and CD8+ T cell responses were also enhanced in both lungs and spleens of mice receiving VLPs adjuvanted with chimeric molecules to various extents. Mice immunized with formalin inactivated RSV (FI-RSV), which are used as the positive control for vaccine induced pathology after RSV challenge developed alveolitis, perivascular infiltration. While all the mice receiving adjuvanted VLP formulations showed protection against lung pathology after RSV challenge.</p><p><strong>Discussion: </strong>The lack of pathology, combined with the robust mucosal and systemic immune responses, suggests that pulmonary delivery of adjuvanted RSV-VLPs may provide effective protection without the risk of vaccine-enhanced disease. The study also demonstrates that the chimeric TLR2/TLR7 agonist CL413 is a promising adjuvant for RSV-VLPs to induce mucosal and systemic immune response and warrant further investigations in more advanced preclinical models.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1561297"},"PeriodicalIF":5.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772115","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}