Yan Yang , Jianmei Sun , Huan You , Yuling Sun , Yizhi Song , Zhouyang Shen , Tongtong Liu , Donglang Guan , Yuan Zhou , Shuo Cheng , Changming Wang , Guang Yu , Chan Zhu , Zongxiang Tang
{"title":"Aloe-emodin relieves allergic contact dermatitis pruritus by inhibiting mast cell degranulation","authors":"Yan Yang , Jianmei Sun , Huan You , Yuling Sun , Yizhi Song , Zhouyang Shen , Tongtong Liu , Donglang Guan , Yuan Zhou , Shuo Cheng , Changming Wang , Guang Yu , Chan Zhu , Zongxiang Tang","doi":"10.1016/j.imlet.2024.106902","DOIUrl":"10.1016/j.imlet.2024.106902","url":null,"abstract":"<div><p>Urushiol-induced allergic contact dermatitis (ACD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to pruritus and eczematous lesions. ACD is triggered by immune imbalance. Aloe emodin is an anthraquinone derivative extracted from rhubarb, aloe and other traditional Chinese medicines. It has a wide range of pharmacological effects, including anti-inflammatory, anti-tumor, and anti-allergic effects. The purpose of our study was to demonstrate the effectiveness of aloe-emodin on urushiol-induced acute pruritus and allergic contact dermatitis. The results showed that urushiol could stimulate keratinocytes to release chemokines CXCL1, CXCL2, CCL2, TSLP, and TNF-α, which recruit or activate mast cells. Aloe-emodin treatment inhibited inflammatory-response-induced mast cell degranulation in skin lesions and suppressed the expression of inflammatory cytokines, such as interleukin-4, and interleukin-6. Therefore, the results indicate that aloe-emodin can improve urushiol-induced acute pruritus and allergic contact dermatitis in mice by inhibiting mast cell degranulation.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106902"},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sherin Bakhashab , Ghalya H Banafea , Farid Ahmed , Reem Alsolami , Hans-Juergen Schulten , Kalamegam Gauthaman , Muhammad Imran Naseer , Peter Natesan Pushparaj
{"title":"Acute and prolonged effects of interleukin-33 on cytokines in human cord blood-derived mast cells","authors":"Sherin Bakhashab , Ghalya H Banafea , Farid Ahmed , Reem Alsolami , Hans-Juergen Schulten , Kalamegam Gauthaman , Muhammad Imran Naseer , Peter Natesan Pushparaj","doi":"10.1016/j.imlet.2024.106908","DOIUrl":"10.1016/j.imlet.2024.106908","url":null,"abstract":"<div><p>Mast cells are multifaceted cells localized in tissues and possess various surface receptors that allow them to respond to inner and external threat signals. Interleukin-33 (IL-33) is a cytokine released by structural cells in response to parasitic infections, mechanical damage, and cell death. IL-33 can activate mast cells, causing them to release an array of mediators. This study aimed to identify the different cytokines released by human cord blood-derived mast cells (hCBMCs) in response to acute and prolonged stimulation with IL-33. For this purpose, a hCBMC model was established and stimulated with 10 ng and 20 ng of recombinant human IL-33 (rhIL-33) for 6 h and 24 h. Total RNA was hybridized using a high-density oligonucleotide microarray. A multiplex assay was performed to assess the released cytokines. Acute exposure to rhIL-33 increased the expression of IL-1α, IL-1β, IL-6, and IL-13, whereas prolonged exposure increased the expression of IL-5 and IL-10, and cytokines were detected in the culture supernatant. WebGestalt analysis revealed that rhIL-33 induces pathways and biological processes related to the immune system and the acute inflammatory response. This study demonstrates that rhIL-33 can activate hCBMCs to release pro- and anti-inflammatory cytokines, eliciting distinct acute and prolonged responses unique to hCBMCs.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106908"},"PeriodicalIF":3.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000828/pdfft?md5=cb2f00bc7f8589edd43ccdc2e5978bf2&pid=1-s2.0-S0165247824000828-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aryane Cruz Oliveira Pinho , Pedro Barbosa , André Lazaro , José G. Tralhão , Maria João Pereira , Artur Paiva , Paula Laranjeira , Eugenia Carvalho
{"title":"Identification and characterization of circulating and adipose tissue infiltrated CD20+ T cells from subjects with obesity that undergo bariatric surgery","authors":"Aryane Cruz Oliveira Pinho , Pedro Barbosa , André Lazaro , José G. Tralhão , Maria João Pereira , Artur Paiva , Paula Laranjeira , Eugenia Carvalho","doi":"10.1016/j.imlet.2024.106911","DOIUrl":"10.1016/j.imlet.2024.106911","url":null,"abstract":"<div><p>T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20<sup>+</sup> <em>T</em> cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20<sup>+</sup> <em>T</em> cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, <em>n</em> = 42), by flow cytometry. Eight subjects were evaluated before (T1) and 12 months post (T2) bariatric/metabolic surgery (BMS). PB from subjects without obesity (nOB, <em>n</em> = 12) was also collected. Higher percentage of CD20<sup>+</sup> <em>T</em> cells was observed in OAT, compared to PB or SAT, in OB-T1. CD20 expression by PB CD4<sup>+</sup> <em>T</em> cells was inversely correlated with adiposity markers, while follicular-like CD20<sup>+</sup> <em>T</em> cells were positively correlated with impaired glucose tolerance (increased HbA1c). Notably, among OB-T1, IR establishment was marked by a lower percentage and absolute number of PB CD20<sup>+</sup> <em>T</em> cells, compared nOB. Obesity was associated with higher percentage of activated CD20<sup>+</sup> <em>T</em> cells; however, OAT-infiltrated CD20<sup>+</sup> <em>T</em> cells from OB-T1 with diabetes displayed the lowest activation. CD20<sup>+</sup> <em>T</em> cells infiltrating OAT from OB-T1 displayed a phenotype towards IFN-γ-producing Th1 and Tc1 cells. After BMS, the percentage of PB CD4<sup>+</sup>CD20<sup>+</sup> <em>T</em> cells increased, with reduced Th1 and increased Th17 phenotype. Whereas in OAT the percentage of CD20<sup>+</sup> <em>T</em> cells with Th1/17 and Tc1/17 phenotypes increased. Interestingly, OAT from OB pre/post BMS maintained higher frequency of effector memory CD20<sup>+</sup> <em>T</em> cells. In conclusion, CD20<sup>+</sup> <em>T</em> cells may play a prominent role in obesity-related AT inflammation.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106911"},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000853/pdfft?md5=6f6c4b2601b82c4cf5897f26533c63d5&pid=1-s2.0-S0165247824000853-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saurav Sharma, Mallar Dasgupta, Bindu Sai Vadaga, Prashant Kodgire
{"title":"Unfolding the symbiosis of AID, chromatin remodelers, and epigenetics–The ACE phenomenon of antibody diversity","authors":"Saurav Sharma, Mallar Dasgupta, Bindu Sai Vadaga, Prashant Kodgire","doi":"10.1016/j.imlet.2024.106909","DOIUrl":"10.1016/j.imlet.2024.106909","url":null,"abstract":"<div><p>Activation-induced cytidine deaminase (AID) is responsible for the initiation of somatic hypermutation (SHM) and class-switch recombination (CSR), which result in antibody affinity maturation and isotype switching, thus producing pathogen-specific antibodies. Chromatin dynamics and accessibility play a significant role in determining AID expression and its targeting. Chromatin remodelers contribute to the accessibility of the chromatin structure, thereby influencing the targeting of AID to Ig genes. Epigenetic modifications, including DNA methylation, histone modifications, and miRNA expression, profoundly impact the regulation of AID and chromatin remodelers targeting Ig genes. Additionally, epigenetic modifications lead to chromatin rearrangement and thereby can change AID expression levels and its preferential targeting to Ig genes. This interplay is symbolized as the ACE phenomenon encapsulates three interconnected aspects: AID, Chromatin remodelers, and Epigenetic modifications. This review emphasizes the importance of understanding the intricate relationship between these aspects to unlock the therapeutic potential of these molecular processes and molecules.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106909"},"PeriodicalIF":3.3,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mucosal associated invariant T cells: Powerhouses of the lung","authors":"J.C. López-Rodríguez , P. Barral","doi":"10.1016/j.imlet.2024.106910","DOIUrl":"10.1016/j.imlet.2024.106910","url":null,"abstract":"<div><p>The lungs face constant environmental challenges from harmless molecules, airborne pathogens and harmful agents that can damage the tissue. The lungs’ immune system includes numerous tissue-resident lymphocytes that contribute to maintain tissue homeostasis and to the early initiation of immune responses. Amongst tissue-resident lymphocytes, Mucosal Associated Invariant T (MAIT) cells are present in human and murine lungs and emerging evidence supports their contribution to immune responses during infections, chronic inflammatory disorders and cancer. This review explores the mechanisms underpinning MAIT cell functions in the airways, their impact on lung immunity and the potential for targeting pulmonary MAIT cells in a therapeutic context.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106910"},"PeriodicalIF":3.3,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000841/pdfft?md5=faec20f743c63c1976bd4cd51ab701c5&pid=1-s2.0-S0165247824000841-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Du , Yurong Zhang , Zhuxin Jiang , Lianjie Xu , Jing Ru , Shanshan Wei , Wenhui Chen , Renjie Dong , Shan Zhang , Tao Jia
{"title":"Triptolide alleviates acute gouty arthritis caused by monosodium urate crystals by modulating macrophage polarization and neutrophil activity","authors":"Yan Du , Yurong Zhang , Zhuxin Jiang , Lianjie Xu , Jing Ru , Shanshan Wei , Wenhui Chen , Renjie Dong , Shan Zhang , Tao Jia","doi":"10.1016/j.imlet.2024.106907","DOIUrl":"10.1016/j.imlet.2024.106907","url":null,"abstract":"<div><p>The present study focused on the efficacy and role of triptolide (TPL) in relieving symptoms of acute gouty arthritis (AGA) <em>in vivo</em> and <em>in vitro</em>. The effects of TPL in AGA were investigated in monosodium urate (MSU)-treated rat ankles, RAW264.7 macrophages, and neutrophils isolated from mouse peritoneal cavity. Observation of pathological changes in the ankle joint of rats. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of inflammatory factors and chemokines. The levels of the indicators of macrophage M1/M2 polarization, and the mechanistic targets of Akt and rapamycin complex 2, were determined via western blotting and RT-qPCR. The expression levels of CD86 and CD206 were detected using immunohistochemistry. Neutrophil migration was observed via air pouch experiments <em>in vivo</em> and Transwell cell migration assay <em>in vitro</em>. Myeloperoxidase (MPO) and Neutrophil elastase (NE) release was analyzed by via immunohistochemistry and immunofluorescence. The expression levels of beclin-1, LC3B, Bax, Bcl-2, and cleaved caspase-3 in neutrophils were determined via western blotting and immunofluorescence. Neutrophil apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Our results suggest that TPL inhibited inflammatory cell infiltration in rat ankle joints and inflammatory factor and chemokine secretion in rat serum, regulated macrophage polarization through the PI3K/AKT signaling pathway, suppressed inflammatory factor and chemokine expression in neutrophils, and inhibited neutrophil migration, neutrophil extracellular trap formation, transitional autophagy, and apoptosis. This suggests that TPL can prevent and treat MSU-induced AGA by regulating macrophage polarization through the PI3K/Akt pathway and modulating neutrophil activity.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106907"},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of CRAMP on the gut-brain axis in experimental sepsis","authors":"Ewerton Vinícius Macarini Bruzaferro, Thais Martins de Lima, Suely Kubo Ariga, Denise Frediani Barbeiro, Hermes Vieira Barbeiro, Fabiano Pinheiro da Silva","doi":"10.1016/j.imlet.2024.106906","DOIUrl":"10.1016/j.imlet.2024.106906","url":null,"abstract":"<div><p>The collaboration between the microbiota, mucosa, and intestinal epithelium is crucial for defending against pathogens and external antigens. Dysbiosis disrupts this balance, allowing pathogens to thrive and potentially enter the bloodstream, triggering immune dysregulation and potentially leading to sepsis. Antimicrobial peptides like LL-37 and CRAMP are pivotal in innate immune defense. Their expression varies with infection severity, exhibiting a dual pro- and anti-inflammatory response. Understanding this dynamic is key to comprehending sepsis progression.</p><p>In our study, we examined the inflammatory response in CRAMP knockout mice post-cecal ligation and puncture (CLP). We assessed its impact on brain tissue damage and the intestinal microbiota. Our findings revealed higher gene expression of S100A8 and S100A9 in the prefrontal cortex of wild-type mice versus CRAMP-knockout mice. This trend was consistent in the hippocampus and cerebellum, although protein concentrations remained constant. Notably, there was a notable increase in <em>Escherichia coli, Lactobacillus</em> spp., and <em>Enterococcus faecalis</em> populations in wild-type mice 24 h post-CLP compared to the CRAMP-deficient group. These results align with our previous data suggesting that the absence of CRAMP may confer protection in this sepsis model.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106906"},"PeriodicalIF":3.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell sequencing has revealed a more complex array of thymic epithelial cells","authors":"Eleonora Pardini , Serena Barachini , Greta Alì , Gisella Sardo Infirri , Irene Sofia Burzi , Marina Montali , Iacopo Petrini","doi":"10.1016/j.imlet.2024.106904","DOIUrl":"10.1016/j.imlet.2024.106904","url":null,"abstract":"<div><p>Thymic epithelial cells participate in the maturation and selection of T lymphocytes. This review explores recent insights from single-cell sequencing regarding classifying thymic epithelial cells in both normal and neoplastic thymus. Cortical thymic epithelial cells facilitate thymocyte differentiation and contribute to positive selection. Medullary epithelial cells are distinguished by their expression of AIRE. Cells progress from a pre-AIRE state, containing precursors with cortical and medullary characteristics, termed junctional cells. Mature medullary epithelial cells exhibit promiscuous gene expression and after that downregulate AIRE mRNA. Post-AIRE cells can adopt a Hassall corpuscle-like phenotype or exhibit distinctive differentiation characteristics including tuft cells, ionocytes, neuroendocrine cells, and myoid cells.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106904"},"PeriodicalIF":3.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000786/pdfft?md5=cad9988cf468c15dbb499bdc23606c93&pid=1-s2.0-S0165247824000786-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Longitudinal analysis at pre- and post-flare of T peripheral helper and T follicular helper subsets in patients with systemic lupus erythematosus","authors":"Noriyasu Seki , Hideto Tsujimoto , Shuhei Tanemura , Jun Kikuchi , Shuntaro Saito , Kunio Sugahara , Keiko Yoshimoto , Mitsuhiro Akiyama , Tsutomu Takeuchi , Kenji Chiba , Yuko Kaneko","doi":"10.1016/j.imlet.2024.106905","DOIUrl":"10.1016/j.imlet.2024.106905","url":null,"abstract":"<div><h3>Objective</h3><p>We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare.</p></div><div><h3>Methods</h3><p>This study included inactive (<em>n</em> = 29) and active (<em>n</em> = 55) patients with SLE. Tph subsets, Tfh subsets, CD11c<sup>hi</sup> B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array.</p></div><div><h3>Results</h3><p>Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare.</p></div><div><h3>Conclusion</h3><p>Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106905"},"PeriodicalIF":3.3,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000798/pdfft?md5=95f2f25c37120c3dbbb1de9cdafb4456&pid=1-s2.0-S0165247824000798-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristina de Oliveira Rodrigues , Julia Spinardi , Regis Goulart Rosa , Maicon Falavigna , Emanuel Maltempi de Souza , Josélia Larger Manfio , Ana Paula de Souza , Cintia Laura Pereira de Araujo , Mírian Cohen , Gynara Rezende Gonzalez do Valle Barbosa , Fernanda Kelly Romeiro Silva , Daniel Sganzerla , Mariana Motta Dias da Silva , Diogo Ferreira , Nicolas Taciano Kunkel , Nathan Iori Camargo , Jean Carlos Sarturi , Márcia Cristina Guilhem , Jaqueline Carvalho de Oliveira , Caroline Cardoso Lopes , John M McLaughlin
{"title":"Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5–11 years of age in Brazil: A prospective test-negative design study","authors":"Cristina de Oliveira Rodrigues , Julia Spinardi , Regis Goulart Rosa , Maicon Falavigna , Emanuel Maltempi de Souza , Josélia Larger Manfio , Ana Paula de Souza , Cintia Laura Pereira de Araujo , Mírian Cohen , Gynara Rezende Gonzalez do Valle Barbosa , Fernanda Kelly Romeiro Silva , Daniel Sganzerla , Mariana Motta Dias da Silva , Diogo Ferreira , Nicolas Taciano Kunkel , Nathan Iori Camargo , Jean Carlos Sarturi , Márcia Cristina Guilhem , Jaqueline Carvalho de Oliveira , Caroline Cardoso Lopes , John M McLaughlin","doi":"10.1016/j.imlet.2024.106903","DOIUrl":"10.1016/j.imlet.2024.106903","url":null,"abstract":"<div><h3>Objective</h3><p>To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5–11 years of age.</p></div><div><h3>Methods</h3><p>This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5–11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated.</p></div><div><h3>Results</h3><p>A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days).</p></div><div><h3>Conclusion</h3><p>In this study with children 5–11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference.</p></div><div><h3>Trial registration number</h3><p>ClinicalTrials.gov number, NCT05403307 (<span><span>https://classic.clinicaltrials.gov/ct2/show/NCT05403307</span><svg><path></path></svg></span>)</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"269 ","pages":"Article 106903"},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}