Immunological memory diversity in the human upper airway

Nature, Год журнала: 2024, Номер 632(8025), С. 630 - 636

Опубликована: Июль 31, 2024

Язык: Английский

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COVID-19 and children

Science, Год журнала: 2022, Номер 377(6611), С. 1144 - 1149

Опубликована: Сен. 8, 2022

There has been substantial research on adult COVID-19 and how to treat it. But do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The pandemic yielded many surprises, not least that children generally develop less disease than older adults, which is unusual for a disease. However, some can serious complications from COVID-19, such as multisystem inflammatory in (MIS-C) Long Covid, even after mild or asymptomatic COVID-19. Why this occurs others an important question. Moreover, when contract understanding their role transmission, especially schools at home, crucial ensuring effective mitigation measures. Therefore, addition nonpharmaceutical interventions, improved ventilation, there strong case vaccinate so reduce possible long-term effects infection decrease transmission. questions remain about whether vaccination might skew immune responses variants the long term. As experts discuss below, more being learned these issues, but much needed understand of children.

Язык: Английский

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T cell immune memory after covid-19 and vaccination

BMJ Medicine, Год журнала: 2023, Номер 2(1), С. e000468 - e000468

Опубликована: Ноя. 1, 2023

The T cell memory response is a crucial component of adaptive immunity responsible for limiting or preventing viral reinfection. after infection with the SARS-CoV-2 virus vaccination broad, and spans multiple proteins epitopes, about 20 in each individual. So far long lasting provides high level cross reactivity hence resistance to escape by variants virus, such as omicron variant. All current vaccine regimens tested produce robust responses, heterologous will probably enhance protective responses through increased breadth. could have major role protecting against severe covid-19 disease rapid clearance early presentation presence reactive cells might this protection. likely provide ongoing protection admission hospital death, development pan-coronovirus future proof new pandemic strains.

Язык: Английский

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Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities

Nature Immunology, Год журнала: 2023, Номер 24(6), С. 966 - 978

Опубликована: Май 29, 2023

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, neutralizing antibodies, receptor-binding domain (RBD) SARS-CoV-2 spike-specific B cells, and CD4+ CD8+ T cells. In participants, RBD IgG antibody titers were correlated with body mass index negatively age. Reduced cells follicular helper in vaccinated participants chronic conditions (diabetes, renal disease) strongly associated altered glycosylation increased interleukin-18 levels the plasma. These perturbations also non-Indigenous people comorbidities, indicating they related comorbidities rather than ethnicity. However, our study is a great importance who have disproportionate rates provides evidence robust after vaccination people.

Язык: Английский

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Defining the balance between optimal immunity and immunopathology in influenza virus infection

Nature reviews. Immunology, Год журнала: 2024, Номер 24(10), С. 720 - 735

Опубликована: Май 2, 2024

Язык: Английский

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Intracranial complications of sinogenic and otogenic infections in children: an ESPN survey on their occurrence in the pre-COVID and post-COVID era

Child s Nervous System, Год журнала: 2024, Номер 40(4), С. 1221 - 1237

Опубликована: Март 8, 2024

Abstract Background COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are intracranial complications sinusitis and otitis (ICSO). According studies on a limited number cases, both streptococci-related ICSO would increased immediately after pandemic, although reason not clear yet (seasonal changes versus pandemic-related effects). The goal present survey European Society for Pediatric Neurosurgery (ESPN) was collect large cases from different countries encompassing pre-COVID (2017–2019), COVID (2020–2021), post-COVID period (2022–June 2023) looking possible epidemiological and/or clinical changes. Material methods An English language questionnaire sent ESPN members about year event, patient’s age gender, presence immune-deficit or other favoring risk factors, infection, signs symptoms at onset, site primary type complication, identified germ, surgical operations, duration medical treatment, radiological outcome, follow-up. Results Two hundred fifty-four were collected by 30 centers coming 14 countries. There statistically significant difference between (129 children, 86 cases/year, 50.7% whole series) (40 20 15.7%) (85 28.3 33.5%). Other differences concerned predisposing factors/concurrent diseases (higher in period) previous infection period). No relevant occurred as far demographic, microbiological, clinical, radiological, morbidity, mortality data concerned. Paranasal sinuses middle ear/mastoid most involved (71% 27%, respectively), while extradural subdural empyema brain abscess common (73% 17%, respectively). Surgery required 95% (neurosurgical ENT procedure 71% 62% respectively) antibiotics 99% cases. After 12.4-month follow-up, full recovery obtained 85% 84% respectively. rate 2.7%. Conclusions These results suggest that occurrence significantly pandemic. Such an increase seems be related indirect effects (e.g., immunity debt) rather than direct effect seasonal fluctuations. remain challenging but did affect management strategies nor their prognosis. change sinusitis/otitis should alert appropriate follow-up children with sinusitis/otitis.

Язык: Английский

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Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan

Nature Immunology, Год журнала: 2023, Номер 24(11), С. 1890 - 1907

Опубликована: Сен. 25, 2023

Abstract CD8 + T cells provide robust antiviral immunity, but how epitope-specific evolve across the human lifespan is unclear. Here we defined cell immunity directed at prominent influenza epitope HLA-A*02:01-M1 58–66 (A2/M1 58 ) four age groups phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence reset in older adults. Gene profiles adults closely resemble those of children, despite being clonally distinct. Only child-derived adult-derived A2/M1 had potential differentiate into highly cytotoxic cells, which was linked public receptor (TCR)αβ signatures. Suboptimal TCRαβ signatures led less proliferation, polyfunctionality, avidity recognition peptide mutants, although displayed no signs exhaustion. These data suggest that priming different stages life might greatly affect responses toward viral infections.

Язык: Английский

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Robust SARS-CoV-2 T cell responses with common TCRαβ motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Cell Reports Medicine, Год журнала: 2023, Номер 4(4), С. 101017 - 101017

Опубликована: Март 27, 2023

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses across three vaccination Seropositivity was low a first dose of BNT162b2 ChAdOx1 (∼26%), increased 59%-75% second dose, 85% third dose. While prototypical antibody-secreting cells (ASCs) T follicular helper (Tfh) cell were elicited healthy participants, showed prolonged ASCs skewed Tfh2/17 responses. Importantly, vaccine-induced expansions spike-specific peptide-HLA tetramer-specific CD4+/CD8+ cells, together with their receptor (TCR) repertoires, robust patients, irrespective B numbers, comparable participants. Vaccinated breakthrough infections developed higher antibody responses, while groups. induces varying diseases treatments numbers response.

Язык: Английский

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The Observed T cell receptor Space database enables paired-chain repertoire mining, coherence analysis and language modelling

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 21, 2024

T cell activation is governed through receptors (TCRs), heterodimers of two sequence-variable chains (often an alpha [ α ] and beta β chain) that recognise linear antigen fragments presented on the surfaces. Early sequencing technologies limited study immune repertoire TCRs to unpaired transcripts, leading extensive analysis -chain data alone as its greater sequence diversity suggested it should dominate recognition. Over time, structural has revealed both contribute binding most antigens highthroughput single-cell handling have been increasingly applied obtain samples complete TCR variable region sequences from repertoires. Despite this, there currently no repository dedicated curation publicly available paired data. We addressed this gap by creating Observed receptor Space (OTS) database, a source consistently processed annotated, full-length, paired-chain 50 studies at least 75 individuals. Currently, OTS contains 5.35M redundant (1.63M nonredundant) predominantly human and, based recent availability trends, will grow rapidly. perform initial OTS, identification pairing biases, public TCRs, distinct chain coherence patterns relative antibodies. also harness build language model, providing embedding representations method for residue in-filling conditional partner chain. be updated maintained central community resource freely downloadable web application https://opig.stats.ox.ac.uk/webapps/ots .

Язык: Английский

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Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273

eLife, Год журнала: 2022, Номер 11

Опубликована: Июль 15, 2022

Patients affected by different types of autoimmune diseases, including common conditions such as multiple sclerosis (MS) and rheumatoid arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral cellular immunity induced infection and/or upon vaccination immunosuppressants.The dynamics immune reactivation SARS-CoV-2 experienced MS patients humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) RA methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry whole blood samples mRNA-1273 (Moderna) vaccine. Longitudinal B T cell responses compared healthy controls (HCs) before 7 days after first second vaccination.OCR-treated exhibit a preserved recall response CD8+ central memory cells following HCs similar CD4+ circulating follicular helper 1 dynamics, whereas strongly impaired resulting in absence SARS-CoV-2-specific immunity. MTX treatment significantly delayed levels vaccination, sustained inhibition overall marker responding cells.Together, these findings indicate that MS-OCR may still benefit from inducing broad which has been associated milder outcome. The vaccine-induced IgG kinetics RA-MTX an increased risk might require additional shielding or alternative strategies interruptions vulnerable patients.This research project was supported ZonMw (The Netherlands Organization for Health Research Development, #10430072010007), European Union's Horizon 2020 innovation program under Marie Skłodowska-Curie grant agreement (#792532 #860003), Commission (SUPPORT-E, #101015756) PPOC (#20_21 L2506), NHMRC Leadership Investigator Grant (#1173871).

Язык: Английский

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