Clinical & Translational Immunology最新文献

{"title":"Advances in bacteria-based drug delivery systems for anti-tumor therapy","authors":"Han Shuwen,&nbsp;Song Yifei,&nbsp;Wu Xinyue,&nbsp;Qu Zhanbo,&nbsp;Yu Xiang,&nbsp;Yang Xi","doi":"10.1002/cti2.1518","DOIUrl":"10.1002/cti2.1518","url":null,"abstract":"<p>In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti-tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria-based drug delivery systems for anti-tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria-based drug systems.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464616","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":"Siglec-1, an easy and contributory inflammation marker in rheumatology","authors":"Valentina Boz,&nbsp;Alessandra Tesser,&nbsp;Francesca Burlo,&nbsp;Nicola Donadel,&nbsp;Serena Pastore,&nbsp;Alessandro Amaddeo,&nbsp;Francesca Vittoria,&nbsp;Matteo Padovan,&nbsp;Marianna Di Rosa,&nbsp;Alberto Tommasini,&nbsp;Erica Valencic","doi":"10.1002/cti2.1520","DOIUrl":"10.1002/cti2.1520","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are poorly informative about interferon (IFN)-related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN-stimulated genes, has been proposed. Flow cytometry-based assays measuring sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression could be a more practical tool for evaluating IFN-inflammation. The study compared Siglec-1 measures with IS and other inflammatory indexes. We compared Siglec-1 measures with IS and other inflammatory indexes in real-world paediatric rheumatology experience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited patients with immuno-rheumatological conditions, acute infectious illness and patients undergoing orthopaedic surgery as controls. Siglec-1 expression was measured in all samples, and IS, ESR and CRP were also recorded if available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 98 subjects were enrolled in the study, with a total of 104 measures of Siglec-1. Compared with IS, Siglec-1 expression showed good accuracy (86.0%), specificity (72.7%) and sensitivity (85.7%). The measure of the percentage of Siglec-1-positive cells performed best at low levels of IFN-inflammation, while the measure of mean fluorescence intensity performed best at higher levels. <i>Ex vivo</i> studies on IFN-stimulated monocytes confirmed this behaviour. There was no link between Siglec-1 expression and either ESR or CRP, and positive Siglec-1 results were found even when ESR and CRP were normal. A high Siglec-1 expression was also recorded in subjects with acute infections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Siglec-1 measurement by flow cytometry is an easy tool to detect IFN-related inflammation, even in subjects with normal results of common inflammation indexes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464617","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":"Serum AZD7442 (tixagevimab–cilgavimab) concentrations and in vitro IC50 values predict SARS-CoV-2 neutralising antibody titres","authors":"Lindsay E Clegg,&nbsp;Oleg Stepanov,&nbsp;Sam Matthews,&nbsp;Tom White,&nbsp;Seth Seegobin,&nbsp;Steven Thomas,&nbsp;Kevin M Tuffy,&nbsp;Mats Någård,&nbsp;Mark T Esser,&nbsp;Katie Streicher,&nbsp;Taylor S Cohen,&nbsp;Anastasia A Aksyuk","doi":"10.1002/cti2.1517","DOIUrl":"10.1002/cti2.1517","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates rapid methods for assessing monoclonal antibody (mAb) potency against emerging variants. Authentic virus neutralisation assays are considered the gold standard for measuring virus-neutralising antibody (nAb) titres in serum. However, authentic virus-based assays pose inherent practical challenges for measuring nAb titres against emerging SARS-CoV-2 variants (e.g. storing infectious viruses and testing at biosafety level-3 facilities). Here, we demonstrate the utility of pseudovirus neutralisation assay data in conjunction with serum mAb concentrations to robustly predict nAb titres in serum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SARS-CoV-2 nAb titres were determined via authentic- and lentiviral pseudovirus-based neutralisation assays using serological data from three AZD7442 (tixagevimab–cilgavimab) studies: PROVENT (NCT04625725), TACKLE (NCT04723394) and a phase 1 dose-ranging study (NCT04507256). AZD7442 serum concentrations were assessed using immunocapture. Serum-based half-maximal inhibitory concentration (IC₅₀) values were derived from pseudovirus nAb titres and serum mAb concentrations, and compared with <i>in vitro</i> IC₅₀ measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>nAb titres measured via authentic- and lentiviral pseudovirus-based neutralisation assays were strongly correlated for the ancestral SARS-CoV-2 virus and SARS-CoV-2 Alpha. Serum AZD7442 concentrations and pseudovirus nAb titres were strongly correlated for multiple SARS-CoV-2 variants with all Spearman correlation coefficients ≥ 0.78. Serum-based IC₅₀ values were similar to <i>in vitro</i> IC₅₀ values for AZD7442, for ancestral SARS-CoV-2 and Alpha, Delta, Omicron BA.2 and Omicron BA.4/5 variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data highlight that serum mAb concentrations and pseudovirus <i>in vitro</i> IC₅₀ values can be used to rapidly predict nAb titres in serum for emerging and historical SARS-CoV-2 variants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11175839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316242","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":"Dupilumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps irrespective of gender: results from the SINUS-52 trial","authors":"Wytske J Fokkens,&nbsp;Claus Bachert,&nbsp;Claire Hopkins,&nbsp;Osama Marglani,&nbsp;Amy Praestgaard,&nbsp;Scott Nash,&nbsp;Yamo Deniz,&nbsp;Paul J Rowe,&nbsp;Harry Sacks,&nbsp;Juby A Jacob-Nara","doi":"10.1002/cti2.1511","DOIUrl":"https://doi.org/10.1002/cti2.1511","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This <i>post hoc</i> analysis assessed disease characteristics and response to dupilumab treatment in male and female patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (SINUS-52 study; NCT02898454).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients received dupilumab 300 mg or placebo every 2 weeks for 52 weeks on background intranasal corticosteroids. Efficacy was assessed through Week 52 using nasal polyp score (NPS), nasal congestion/obstruction score, loss of smell score and University of Pennsylvania Smell Identification Test score. Disease-specific health-related quality of life (HRQoL) was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 192 male and 111 female patients. Female patients had higher mean SNOT-22 total score (56.6 vs. 49.1, <i>P</i> &lt; 0.01) and more coexisting asthma (78.4% vs. 46.4%, <i>P</i> &lt; 0.0001) and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) (38.7% vs. 18.8%, <i>P</i> = 0.0001) than male patients, but other baseline characteristics were similar. Dupilumab significantly improved CRSwNP outcomes vs. placebo at Week 52, regardless of gender: least squares mean differences (95% confidence interval) for NPS were −2.33 (−2.80, −1.86) in male and −2.54 (−3.18, −1.90) in female patients (both <i>P</i> &lt; 0.0001 vs. placebo), and for SNOT-22 were −19.2 (−24.1, −14.2) in male and −24.4 (−31.5, −17.3) in female patients (both <i>P</i> &lt; 0.0001 vs. placebo). There were no significant efficacy-by-gender interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Female patients had greater asthma, NSAID-ERD and HRQoL burden at baseline than male patients. Dupilumab treatment significantly improved objective and subjective outcomes compared with placebo, irrespective of gender.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141292571","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":"Characterisation of circulating tumor-associated and immune cells in patients with advanced-stage non-small cell lung cancer","authors":"Vahid Yaghoubi Naei,&nbsp;Ekaterina Ivanova,&nbsp;William Mullally,&nbsp;Connor G O'Leary,&nbsp;Rahul Ladwa,&nbsp;Ken O'Byrne,&nbsp;Majid E Warkiani,&nbsp;Arutha Kulasinghe","doi":"10.1002/cti2.1516","DOIUrl":"https://doi.org/10.1002/cti2.1516","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Globally, non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and the leading cause of cancer-related deaths. Tumor-associated circulating cells in NSCLC can have a wide variety of morphological and phenotypic characteristics, including epithelial, immunological or hybrid subtypes. The distinctive characteristics and potential clinical significance of these cells in patients with NSCLC are explored in this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilised a spiral microfluidic device to enrich large cells and cell aggregates from the peripheral blood samples of NSCLC patients. These cells were characterised through high-resolution immunofluorescent imaging and statistical analysis, correlating findings with clinical information from our patient cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We have identified varied populations of heterotypic circulating tumor cell clusters with differing immune cell composition that included a distinct class of atypical tumor-associated macrophages that exhibits unique morphology and cell size. This subtype's prevalence is positively correlated with the tumor stage, progression and metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study reveals a heterogeneous landscape of circulating tumor cells and their clusters, underscoring the complexity of NSCLC pathobiology. The identification of a unique subtype of atypical tumor-associatedmacrophages that simultaneously express both tumor and immune markers and whose presence correlates with late disease stages, poor clinical outcomes and metastatic risk infers  the potential of these cells as biomarkers for NSCLC staging and prognosis. Future studies should focus on the role of these cells in the tumor microenvironment and their potential as therapeutic targets. Additionally, longitudinal studies tracking these cell types through disease progression could provide further insights into their roles in NSCLC evolution and response to treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141245980","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":"Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma","authors":"Yu-Min Zhong,&nbsp;Ji Chen,&nbsp;Jie Jiang,&nbsp;Wen-Bin Zhou,&nbsp;Ling-Ling Gao,&nbsp;Shui-Lian Zhang,&nbsp;Wen-Qing Yan,&nbsp;Yu Chen,&nbsp;Dong-Kun Zhang,&nbsp;Dan-Xia Lu,&nbsp;Zhi-Yi Lv,&nbsp;Zhi Xie,&nbsp;Ying Huang,&nbsp;Wei-Bang Guo,&nbsp;Bin-Chao Wang,&nbsp;Jin-Ji Yang,&nbsp;Xue-Ning Yang,&nbsp;Yi-Long Wu,&nbsp;Xu-Chao Zhang","doi":"10.1002/cti2.1515","DOIUrl":"https://doi.org/10.1002/cti2.1515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein–Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral <i>EBNA-1</i> and <i>BamHI-W</i> DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Progression-free survival (PFS) was significantly longer in <i>EBNA-1</i> high or <i>BamHI-W</i> high groups. A longer PFS was also observed in patients with both high plasma <i>EBNA-1</i> or <i>BamHI-W</i> and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with <i>EBNA-1</i> and <i>BamHI-W</i>. Plasma EBV load was negatively associated with intratumoral CD8⁺ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141245979","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":"Engineered CAR-T cells targeting the non-functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer","authors":"Veronika Bandara,&nbsp;Victoria M Niktaras,&nbsp;Vasiliki J Willett,&nbsp;Hayley Chapman,&nbsp;Noor A Lokman,&nbsp;Anne M Macpherson,&nbsp;Silvana Napoli,&nbsp;Batjargal Gundsambuu,&nbsp;Jade Foeng,&nbsp;Timothy J Sadlon,&nbsp;Justin Coombs,&nbsp;Shaun R McColl,&nbsp;Simon C Barry,&nbsp;Martin K Oehler,&nbsp;Carmela Ricciardelli","doi":"10.1002/cti2.1512","DOIUrl":"https://doi.org/10.1002/cti2.1512","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Recent studies have identified expression of the non-functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour-associated antigen candidate for chimeric antigen receptor (CAR)-T-cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7-CAR-T cells on ovarian cancer using <i>in vitro</i> and <i>in vivo</i> models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the effects of nfP2X7-CAR-T cells on ovarian cancer cell lines (SKOV-3, OVCAR3, OVCAR5), normal peritoneal cells (LP-9) and primary serous ovarian cancer cells derived from patient ascites <i>in vitro</i> using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7-CAR-T cells on patient-derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7-CAR-T cells <i>in vivo</i> using the OVCAR-3 xenograft model in NOD-scid IL2Rγnull (NSG) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study found that nfP2X7-CAR-T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un-transduced CD3⁺ T cells <i>in vitro</i>. However, no significant effects of nfP2X7-CAR-T cells were observed for SKOV3 or normal peritoneal cells (LP-9) cells with low P2X7 receptor expression. Treatment with nfP2X7-CAR-T cells increased apoptosis compared with un-transduced T cells in patient-derived explants and correlated with CD3 positivity. Treatment with nfP2X7-CAR-T cells significantly reduced OVCAR3 tumour burden in mice compared with un-transduced CD3 cells for 7–8 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that nfP2X7-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141091440","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":"From intramuscular to nasal: unleashing the potential of nasal spray vaccines against coronavirus disease 2019","authors":"Ge Jin,&nbsp;Runze Wang,&nbsp;Yi Jin,&nbsp;Yingqiu Song,&nbsp;Tianlu Wang","doi":"10.1002/cti2.1514","DOIUrl":"https://doi.org/10.1002/cti2.1514","url":null,"abstract":"<p>Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected 700 million people worldwide since its outbreak in 2019. The current pandemic strains, including Omicron and its large subvariant series, exhibit strong transmission and stealth. After entering the human body, the virus first infects nasal epithelial cells and invades host cells through the angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 on the host cell surface. The nasal cavity is an important body part that protects against the virus. Immunisation of the nasal mucosa produces immunoglobulin A antibodies that effectively neutralise viruses. Saline nasal irrigation, a type of physical therapy, can reduce the viral load in the nasal cavity and prevent viral infections to some extent. As a commonly used means to fight SARS-CoV-2, the intramuscular (IM) vaccine can induce the human body to produce a systemic immune response and immunoglobulin G antibody; however, the antibody is difficult to distribute to the nasal mucosa in time and cannot achieve a good preventive effect. Intranasal (IN) vaccines compensate for the shortcomings of IM vaccines, induce mucosal immune responses, and have a better effect in preventing infection. In this review, we discuss the nasal defence barrier, the harm caused by SARS-CoV-2, the mechanism of its invasion into host cells, nasal cleaning, IM vaccines and IN vaccines, and suggest increasing the development of IN vaccines, and use of IN vaccines as a supplement to IM vaccines.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069092","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":"Characterisation of novel influenza-derived HLA-B*18:01-restricted epitopes","authors":"Samuel Liwei Leong,&nbsp;Lawton Murdolo,&nbsp;Janesha C Maddumage,&nbsp;Marios Koutsakos,&nbsp;Katherine Kedzierska,&nbsp;Anthony W Purcell,&nbsp;Stephanie Gras,&nbsp;Emma J Grant","doi":"10.1002/cti2.1509","DOIUrl":"https://doi.org/10.1002/cti2.1509","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8⁺ T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8⁺ T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I). Each HLA-I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8⁺ T cell responses across broad populations. Consequently, the rational design of a CD8⁺ T cell-mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we assessed the immunogenicity of six recently published novel influenza-derived peptides identified by mass-spectrometry and predicted to bind to the prevalent HLA-B*18:01 molecule.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using CD8⁺ T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*18:01⁺ individuals and confirmed their HLA-B*18:01 restriction. We subsequently compared CD8⁺ T cell responses towards the previously identified highly immunogenic HLA-B*18:01-restricted NP₂₁₉ peptide. Using X-ray crystallography, we solved the first crystal structures of HLA-B*18:01 presenting immunogenic influenza-derived peptides. Finally, we dissected the first TCR repertoires specific for HLA-B*18:01 restricted pathogen-derived peptides, identifying private and restricted repertoires against each of the four peptides.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall the characterisation of these novel immunogenic peptides provides additional HLA-B*18:01-restricted vaccine targets derived from the Matrix protein 1 and potentially the non-structural protein and the RNA polymerase catalytic subunit of influenza viruses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907042","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":"Effects of extremely preterm birth on cytokine and chemokine responses induced by T-cell activation during infancy","authors":"Dhanapal Govindaraj,&nbsp;Georg Bach Jensen,&nbsp;Khaleda Rahman Qazi,&nbsp;Eva Sverremark-Ekström,&nbsp;Thomas Abrahamsson,&nbsp;Maria C Jenmalm","doi":"10.1002/cti2.1510","DOIUrl":"https://doi.org/10.1002/cti2.1510","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Extremely preterm (EPT; gestational week &lt; 28 + 0, &lt; 1000 g) neonates are vulnerable to infections and necrotising enterocolitis, important contributors to mortality and morbidity. However, knowledge regarding their immune maturation remains limited. We here investigated the longitudinal development of functional T-cell capacity in EPT infants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells were isolated at 14th and 28th day (D) and at gestational week 36 + 0 (Gw36) from EPT infants, participated in a randomised, double-blind, placebo-controlled study of <i>Lactobacillus reuteri</i> DSM 17938 probiotic supplementation. Blood collected from 25 full-term (FT) infants at D14 was used as control. The secretion of immune mediators was determined through comprehensive Luminex panels after stimulation with human T-cell activator CD3/CD28 beads.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The levels of many mediators were low in EPT infants at D14, whereas the secretion of several chemokines was higher in EPT than in FT infants. Furthermore, Th2:Th1 cytokine ratios were higher in EPT than in FT infants. Progressively elevated secretion of, for example, IFN-γ, TNF and IL-17A in EPT infants was observed from D14 to D28 and then at Gw36. Elevated levels were observed for many proinflammatory mediators at D28. Probiotic supplementation or perinatal factors (e.g. clinical chorioamnionitis, preeclampsia and delivery mode) did not influence the cytokine and chemokine responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Immune mediators induced by T-cell activation in EPT infants were mainly reduced at D14 and Th2 skewed compared to those in FT infants, but mostly recovered at Gw36, indicating immune maturation. Increased proinflammatory responses at D28 may be related to the heightened risk of severe immune-associated complications seen in EPT infants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907041","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}