Clinical & Translational Immunology最新文献

{"title":"Diversification of circulating and tumor-infiltrating plasmacytoid DCs towards the P3 (CD80+ PDL1−)-pDC subset negatively correlated with clinical outcomes in melanoma patients","authors":"Eleonora Sosa Cuevas,&nbsp;Nathalie Bendriss-Vermare,&nbsp;Stephane Mouret,&nbsp;Florence De Fraipont,&nbsp;Julie Charles,&nbsp;Jenny Valladeau-Guilemond,&nbsp;Laurence Chaperot,&nbsp;Caroline Aspord","doi":"10.1002/cti2.1382","DOIUrl":"https://doi.org/10.1002/cti2.1382","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Plasmacytoid DCs (pDCs) play a critical yet enigmatic role in antitumor immunity through their pleiotropic immunomodulatory functions. Despite proof of pDC diversity in several physiological or pathological contexts, pDCs have been studied as a whole population so far in cancer. The assessment of individual pDC subsets is needed to fully grasp their involvement in cancer immunity, especially in melanoma where pDC subsets are largely unknown and remain to be uncovered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We explored for the first time the features of diverse circulating and tumor-infiltrating pDC subsets in melanoma patients using multi-parametric flow cytometry, and assessed their clinical relevance. Based on CD80, PDL1, CD2, LAG3 and Axl markers, we provided an integrated overview of the frequency, basal activation status and functional features of pDC subsets in melanoma patients together with their relationship to clinical outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Strikingly, we demonstrated that P3-pDCs (CD80⁺PDL1⁻) accumulated within the tumor of melanoma patients and negatively correlated with clinical outcomes. The basal activation status, diversification towards P1-/P2-/P3-pDCs and functionality of several pDC subsets upon TLR7/TLR9 triggering were perturbed in melanoma patients, and were differentially linked to clinical outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study shed light for the first time on the phenotypic and functional heterogeneity of pDCs in the blood and tumor of melanoma patients and their potential involvement in shaping clinical outcomes. Such novelty brightens our understanding of pDC complexity, and prompts the further deciphering of pDCs’ features to better apprehend and exploit these potent immune players. It highlights the importance of considering pDC diversity when developing pDC-based therapeutic strategies to ensure optimal clinical success.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6106276","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":"Humoral immunity against SARS-CoV-2 variants including omicron in solid organ transplant recipients after three doses of a COVID-19 mRNA vaccine","authors":"Kapil K Saharia,&nbsp;Jennifer S Husson,&nbsp;Silke V Niederhaus,&nbsp;Thierry Iraguha,&nbsp;Stephanie V Avila,&nbsp;Youngchae J Yoo,&nbsp;Nancy M Hardy,&nbsp;Xiaoxuan Fan,&nbsp;Destiny Omili,&nbsp;Alice Crane,&nbsp;Amber Carrier,&nbsp;Wen Y Xie,&nbsp;Erica Vander Mause,&nbsp;Kim Hankey,&nbsp;Sherri Bauman,&nbsp;Patricia Lesho,&nbsp;Heather D Mannuel,&nbsp;Ashish Ahuja,&nbsp;Minu Mathew,&nbsp;James Avruch,&nbsp;John Baddley,&nbsp;Olga Goloubeva,&nbsp;Kirti Shetty,&nbsp;Saurabh Dahiya,&nbsp;Aaron P Rapoport,&nbsp;Tim Luetkens,&nbsp;Djordje Atanackovic","doi":"10.1002/cti2.1391","DOIUrl":"https://doi.org/10.1002/cti2.1391","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Solid organ transplant recipients (SOTR) receiving post-transplant immunosuppression show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines can overcome the reduced immune responsiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed humoral immune responses against SARS-CoV-2 and its variants in 53 SOTR receiving SARS-CoV-2 vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following the initial vaccination series, 60.3% of SOTR showed no measurable neutralisation and only 18.9% demonstrated neutralising activity of &gt; 90%. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titres against microbial recall antigens were higher. By contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titres against SARS-CoV-2 and its delta variants and fewer linear B-cell epitopes, indicating reduced B-cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titres and neutralising activity across alpha, beta and delta variants and to the induction of anti-SARS-CoV-2 CD4⁺ T cells in a subgroup of patients analysed. By contrast, we observed significantly lower antibody titres after the third dose with the omicron variant compared to the ancestral SARS-CoV-2 and the improvement in neutralising activity was much less pronounced than for all the other variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Only a small subgroup of solid organ transplant recipients is able to generate functional antibodies after an initial vaccine series; however, an additional vaccine dose resulted in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron where antibody responses and neutralising activity remained suboptimal.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 5","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5873725","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":"Validation and performance of a multiplex serology assay to quantify antibody responses following SARS-CoV-2 infection or vaccination","authors":"Deidre Wilkins,&nbsp;Anastasia A Aksyuk,&nbsp;Alexey Ruzin,&nbsp;Kevin M Tuffy,&nbsp;Tina Green,&nbsp;Rebecca Greway,&nbsp;Brittany Fikes,&nbsp;Cyrille J Bonhomme,&nbsp;Mark T Esser,&nbsp;Elizabeth J Kelly","doi":"10.1002/cti2.1385","DOIUrl":"https://doi.org/10.1002/cti2.1385","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Robust, quantitative serology assays are required to accurately measure antibody levels following vaccination and natural infection. We present validation of a quantitative, multiplex, SARS-CoV-2, electrochemiluminescent (ECL) serology assay; show correlation with two established SARS-CoV-2 immunoassays; and present calibration results for two SARS-CoV-2 reference standards.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Precision, dilutional linearity, ruggedness, analytical sensitivity and specificity were evaluated. Clinical sensitivity and specificity were assessed using serum from prepandemic and SARS-CoV-2 polymerase chain reaction (PCR)-positive patient samples. Assay concordance to the established Roche Elecsys® Anti-SARS-CoV-2 immunoassay and a live-virus microneutralisation (MN) assay was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Standard curves demonstrated the assay can quantify SARS-CoV-2 antibody levels over a broad range. Assay precision (10.2−15.1% variability), dilutional linearity (≤ 1.16-fold bias per 10-fold increase in dilution), ruggedness (0.89−1.18 overall fold difference), relative accuracy (107−118%) and robust selectivity (102−104%) were demonstrated. Analytical sensitivity was 7, 13 and 7 arbitrary units mL⁻¹ for SARS-CoV-2 spike (S), receptor-binding domain (RBD) and nucleocapsid (N) antigens, respectively. For all antigens, analytical specificity was &gt; 90% and clinical specificity was 99.0%. Clinical sensitivities for S, RBD and N antigens were 100%, 98.8% and 84.9%, respectively. Comparison with the Elecsys® immunoassay showed ≥ 87.7% agreement and linear correlation (Pearson <i>r</i> of 0.85, <i>P</i> &lt; 0.0001) relative to the MN assay. Conversion factors for the WHO International Standard and Meso Scale Discovery® Reference Standard are presented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The multiplex SARS-CoV-2 ECL serology assay is suitable for efficient, reproducible measurement of antibodies to SARS-CoV-2 antigens in human sera, supporting its use in clinical trials and sero-epidemiology studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5721158","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":"Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients","authors":"Luciana Ribeiro Jarduli-Maciel,&nbsp;Júlia Teixeira Cottas de Azevedo,&nbsp;Emmanuel Clave,&nbsp;Thalita Cristina de Mello Costa,&nbsp;Lucas Coelho Marlière Arruda,&nbsp;Isabelle Fournier,&nbsp;Patrícia Vianna Bonini Palma,&nbsp;Keli Cristina Lima,&nbsp;Juliana Bernardes Elias,&nbsp;Ana Beatriz PL Stracieri,&nbsp;Fabiano Pieroni,&nbsp;Renato Cunha,&nbsp;Luiz Guilherme Darrigo-Júnior,&nbsp;Carlos Eduardo Settani Grecco,&nbsp;Dimas Tadeu Covas,&nbsp;Ana Cristina Silva-Pinto,&nbsp;Gil Cunha De Santis,&nbsp;Belinda Pinto Sim?es,&nbsp;Maria Carolina Oliveira,&nbsp;Antoine Toubert,&nbsp;Kelen Cristina Ribeiro Malmegrim","doi":"10.1002/cti2.1389","DOIUrl":"https://doi.org/10.1002/cti2.1389","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). Here, we comprehensively evaluated the reconstitution of T- and B-cell compartments in 29 SCD patients treated with allo-HSCT and how it correlated with the development of acute graft-versus-host disease (aGvHD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T-cell neogenesis was assessed by quantification of signal-joint and β-chain TCR excision circles. B-cell neogenesis was evaluated by quantification of signal-joint and coding-joint K-chain recombination excision circles. T- and B-cell peripheral subset numbers were assessed by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Before allo-HSCT (baseline), T-cell neogenesis was normal in SCD patients compared with age-, gender- and ethnicity-matched healthy controls. Following allo-HSCT, T-cell neogenesis declined but was fully restored to healthy control levels at one year post-transplantation. Peripheral T-cell subset counts were fully restored only at 24 months post-transplantation. Occurrence of acute graft-versus-host disease (aGvHD) transiently affected T- and B-cell neogenesis and overall reconstitution of T- and B-cell peripheral subsets. B-cell neogenesis was significantly higher in SCD patients at baseline than in healthy controls, remaining high throughout the follow-up after allo-HSCT. Notably, after transplantation SCD patients showed increased frequencies of IL-10-producing B-regulatory cells and IgM⁺ memory B-cell subsets compared with baseline levels and with healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings revealed that the T- and B-cell compartments were normally reconstituted in SCD patients after allo-HSCT. In addition, the increase of IL-10-producing B-regulatory cells may contribute to improve immune regulation and homeostasis after transplantation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5812813","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":"Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19","authors":"Nicole L Messina,&nbsp;Susie Germano,&nbsp;Rebecca McElroy,&nbsp;Rajeev Rudraraju,&nbsp;Rhian Bonnici,&nbsp;Laure F Pittet,&nbsp;Melanie R Neeland,&nbsp;Suellen Nicholson,&nbsp;Kanta Subbarao,&nbsp;Nigel Curtis,&nbsp;the BRACE trial","doi":"10.1002/cti2.1387","DOIUrl":"https://doi.org/10.1002/cti2.1387","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and objectives</h3>\u0000 \u0000 <p>Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on <i>in vitro</i> immune responses to SARS-CoV-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4⁺ and CD8⁺ T cells, and an activation of eosinophils in response to SARS-CoV-2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5766844","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":"Deficient DNASE1L3 facilitates neutrophil extracellular traps-induced invasion via cyclic GMP-AMP synthase and the non-canonical NF-κB pathway in diabetic hepatocellular carcinoma","authors":"Na Li,&nbsp;Xue Zheng,&nbsp;Mianrong Chen,&nbsp;Li Huang,&nbsp;Li Chen,&nbsp;Rui Huo,&nbsp;Xiaotong Li,&nbsp;Yucan Huang,&nbsp;Mingwen Sun,&nbsp;Suiqing Mai,&nbsp;Zhuoyi Wu,&nbsp;Hui Zhang,&nbsp;Jinbao Liu,&nbsp;Chun-tao Yang","doi":"10.1002/cti2.1386","DOIUrl":"https://doi.org/10.1002/cti2.1386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Diabetic hepatocellular carcinoma (HCC) patients have high mortality and metastasis rates. Diabetic conditions promote neutrophil extracellular traps (NETs) generation, which mediates HCC metastasis and invasion. However, whether and how diabetes-induced NETs trigger HCC invasion is largely unknown. Here, we aimed to observe the effects of diabetes-induced NETs on HCC invasion and investigate mechanisms relevant to a DNA sensor cyclic GMP-AMP synthase (cGAS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Serum from diabetic patients and healthy individuals was collected. Human neutrophil-derived NETs were isolated for stimulating HCC cell invasion. Data from the SEER and TCGA databases were used for bioinformatics analysis. In HCC cells and allograft models, NETs-triggered invasion was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Diabetic HCC patients had poorer survival than non-diabetic ones. Either diabetic serum or extracted NETs caused HCC invasion. Induction of diabetes or NETosis elicited HCC allograft invasion in nude mice. HCC cell invasion was attenuated by the treatment with DNase1. In TCGA_LIHC, an extracellular DNase DNASE1L3 was downregulated in tumor tissues, while function terms (the endocytic vesicle membrane, the NF-κB pathway and extracellular matrix disassembly) were enriched. DNASE1L3 knockdown in LO2 hepatocytes or H22 cell-derived allografts facilitated HCC invasion in NETotic or diabetic nude mice. Moreover, exposure of HCC cells to NETs upregulated cGAS and the non-canonical NF-κB pathway and induced expression of metastasis genes (<i>MMP9</i> and <i>SPP1</i>). Both cGAS inhibitor and NF-κB RELB knockdown diminished HCC invasion caused by NETs DNA. Also, cGAS inhibitor was able to retard translocation of NF-κB RELB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Defective DNASE1L3 aggravates NETs DNA-triggered HCC invasion on diabetic conditions via cGAS and the non-canonical NF-κB pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5725645","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":"Impact of SARS-CoV-2 infection on vaccine-induced immune responses over time","authors":"Sebastian Havervall,&nbsp;Ulrika Marking,&nbsp;Nina Greilert-Norin,&nbsp;Max Gordon,&nbsp;Henry Ng,&nbsp;Wanda Christ,&nbsp;Mia Phillipson,&nbsp;Peter Nilsson,&nbsp;Sophia Hober,&nbsp;Kim Blom,&nbsp;Jonas Klingstr?m,&nbsp;Sara Mangsbo,&nbsp;Mikael ?berg,&nbsp;Charlotte Th?lin","doi":"10.1002/cti2.1388","DOIUrl":"https://doi.org/10.1002/cti2.1388","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the long-term impact of prior SARS-CoV-2 infection on immune responses after COVID-19 vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU mL⁻¹) and neutralising antibody titres against ten SARS-CoV-2 variants over 7 months following BNT162b2 in SARS-CoV-2-recovered (<i>n</i> = 118) and SARS-CoV-2-naïve (<i>n</i> = 289) healthcare workers with confirmed prior SARS-CoV-2 infection. A smaller group with (<i>n</i> = 47) and without (<i>n</i> = 60) confirmed prior SARS-CoV-2 infection receiving ChAdOx1 nCoV-19 was followed for 3 months. SARS-CoV-2-specific memory T-cell responses were investigated in a subset of SARS-CoV-2-naïve and SARS-CoV-2-recovered vaccinees.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vaccination with both vaccine platforms resulted in substantially enhanced T-cell responses, anti-spike IgG responses and neutralising antibodies effective against ten SARS-CoV-2 variants in SARS-CoV-2-recovered participants as compared to SARS-CoV-2-naïve participants. The enhanced immune responses sustained over 7 months following vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings imply that prior SARS-CoV-2 infection should be taken into consideration when planning booster doses and design of current and future COVID-19 vaccine programmes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5682871","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":"Severe COVID-19 represents an undiagnosed primary immunodeficiency in a high proportion of infected individuals","authors":"Paul E Gray,&nbsp;Adam W Bartlett,&nbsp;Stuart G Tangye","doi":"10.1002/cti2.1365","DOIUrl":"https://doi.org/10.1002/cti2.1365","url":null,"abstract":"<p>Since the emergence of the COVID-19 pandemic in early 2020, a key challenge has been to define risk factors, other than age and pre-existing comorbidities, that predispose some people to severe disease, while many other SARS-CoV-2-infected individuals experience mild, if any, consequences. One explanation for intra-individual differences in susceptibility to severe COVID-19 may be that a growing percentage of otherwise healthy people have a pre-existing asymptomatic primary immunodeficiency (PID) that is unmasked by SARS-CoV-2 infection. Germline genetic defects have been identified in individuals with life-threatening COVID-19 that compromise local type I interferon (IFN)-mediated innate immune responses to SARS-CoV-2. Remarkably, these variants – which impact responses initiated through TLR3 and TLR7, as well as the response to type I IFN cytokines – may account for between 3% and 5% of severe COVID-19 in people under 70 years of age. Similarly, autoantibodies against type I IFN cytokines (IFN-α, IFN-ω) have been detected in patients' serum prior to infection with SARS-CoV-2 and were found to cause <i>c</i>. 20% of severe COVID-19 in the above 70s and 20% of total COVID-19 deaths. These autoantibodies, which are more common in the elderly, neutralise type I IFNs, thereby impeding innate antiviral immunity and phenocopying an inborn error of immunity. The discovery of PIDs underlying a significant percentage of severe COVID-19 may go some way to explain disease susceptibility, may allow for the application of targeted therapies such as plasma exchange, IFN-α or IFN-β, and may facilitate better management of social distancing, vaccination and early post-exposure prophylaxis.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5693125","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":"LUNG group 2 innate lymphoid cells as a new adjuvant target to enhance intranasal vaccine efficacy against influenza","authors":"Clare M Williams,&nbsp;Sreeja Roy,&nbsp;Wei Sun,&nbsp;Andrea M Furuya,&nbsp;Danushka K Wijesundara,&nbsp;Yoichi Furuya","doi":"10.1002/cti2.1381","DOIUrl":"https://doi.org/10.1002/cti2.1381","url":null,"abstract":"<p>Group 2 innate lymphoid cells (ILC2) are a relatively new class of innate immune cells. Lung ILC2 are early responders that secrete type 2 cytokines in response to danger ‘alarmin’ signals such as interleukin (IL)-33 and thymic stromal lymphopoietin. Being an early source of type 2 cytokines, ILC2 are a critical regulator of type 2 immune cells of both innate and adaptive immune responses. The immune regulatory functions of ILC2 were mostly investigated in diseases where T helper 2 inflammation predominates. However, in recent years, it has been appreciated that the role of ILC2 extends to other pathological conditions such as cancer and viral infections. In this review, we will focus on the potential role of lung ILC2 in the induction of mucosal immunity against influenza virus infection and discuss the potential utility of ILC2 as a target for mucosal vaccination.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5851803","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":"A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination","authors":"Karen Colwill,&nbsp;Yannick Galipeau,&nbsp;Matthew Stuible,&nbsp;Christian Gervais,&nbsp;Corey Arnold,&nbsp;Bhavisha Rathod,&nbsp;Kento T Abe,&nbsp;Jenny H Wang,&nbsp;Adrian Pasculescu,&nbsp;Mariam Maltseva,&nbsp;Lynda Rocheleau,&nbsp;Martin Pelchat,&nbsp;Mahya Fazel-Zarandi,&nbsp;Mariam Iskilova,&nbsp;Miriam Barrios-Rodiles,&nbsp;Linda Bennett,&nbsp;Kevin Yau,&nbsp;Fran?ois Cholette,&nbsp;Christine Mesa,&nbsp;Angel X Li,&nbsp;Aimee Paterson,&nbsp;Michelle A Hladunewich,&nbsp;Pamela J Goodwin,&nbsp;Jeffrey L Wrana,&nbsp;Steven J Drews,&nbsp;Samira Mubareka,&nbsp;Allison J McGeer,&nbsp;John Kim,&nbsp;Marc-André Langlois,&nbsp;Anne-Claude Gingras,&nbsp;Yves Durocher","doi":"10.1002/cti2.1380","DOIUrl":"https://doi.org/10.1002/cti2.1380","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our single-point IgG-based ELISAs accurately distinguished non-infected and infected individuals. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike-ACE2 interactions in high-throughput enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter-laboratory data comparison and aggregation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2022-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5790401","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}