Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant

Cell Host & Microbe, Год журнала: 2024, Номер 32(2), С. 156 - 161.e3

Опубликована: Янв. 10, 2024

T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory can effectively cross-recognize new SARS-CoV-2 variants with a broad array mutations, such as emergent hypermutated BA.2.86 variant. Here, we report two separate cohorts, including healthy controls and individuals chronic lymphocytic leukemia, that spike-specific CD4

Язык: Английский

---

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 10, 2025

Abstract Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim understand the host immunologic and microbial features of COVID-19 in recipients by leveraging a prospective multicenter cohort 86 age- sex-matched with 172 non-transplant controls. find that higher nasal SARS-CoV-2 viral abundance impaired clearance, lower anti-spike IgG levels. In addition, exhibit decreased plasmablasts transitional B cells, increased senescent T cells. Blood transcriptional profiling demonstrate unexpected upregulation innate signaling pathways levels several proinflammatory serum chemokines. Severe however, is less robust induction pro-inflammatory genes Together, our study reveals distinct altered dynamics recipients.

Язык: Английский

---

Severe Acute Respiratory Syndrome Coronavirus 2 Immunology and Coronavirus Disease 2019 Clinical Outcomes

Infectious Disease Clinics of North America, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

---

Deconvoluting TCR-dependent and -independent activation is vital for reliable Ag-specific CD4 ⁺ T cell characterization by AIM assay

Science Advances, Год журнала: 2025, Номер 11(17)

Опубликована: Апрель 25, 2025

Activation-induced marker (AIM) assays identify antigen (Ag)–specific T cells, but recent studies revealed AIM + helper cell 17 (T H 17)–like (CCR6 ) and circulating follicular cells (cTfh) were not associated with peptide/HLA tetramer staining. We show that CD39 regulatory reg )–like CD26 hi 22–like undergo receptor (TCR)–independent activation by cytokines during Ag stimulation, leading to nonspecific up-regulation of readouts. Transcriptional analysis enabled discrimination bona fide Ag-specific from cytokine-activated 22 cells. CXCR4 down-regulation emerged as a hallmark clonotypic expansion TCR-dependent in memory CD4 cTfh. By tracking tetramer-binding upon restimulation, we demonstrated CXCR4−CD137 provided more accurate measure Ag-specificity than standard This modified assay excluded the predominantly CCR6 contributed an average 12-fold overestimation population. Our findings provide approach characterize genuine

Язык: Английский

---

Combining SARS‐CoV‐2 interferon‐gamma release assay with humoral response assessment to define immune memory profiles

European Journal of Immunology, Год журнала: 2024, Номер 54(7)

Опубликована: Апрель 16, 2024

Abstract Objectives In the post‐SARS‐CoV‐2 pandemic era, “breakthrough infections” are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, definition anti‐Spike (S) immunoglobulin‐G (IgG) threshold define protection has unveiled several limitations. Here, we explore advantages incorporating T‐cell response assessment enhance immune memory profile. Methods SARS‐CoV‐2 interferon‐gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti‐receptor‐binding domain IgG levels were assessed in parallel. The risk symptomatic according cellular/humoral capacities during Omicron BA.1 wave then estimated. Results Close 40% our exclusively IGRA‐positive, largely time elapsed since last immunization. This suggests that individuals have sustained long‐lasting cellular immunity, while they would been classified as lacking protective immunity based solely threshold. Moreover, Cox regression model highlighted circulation raises increased IGRA tended reduce it. Conclusion discrepancy between responses highlights significance assessing overall adaptive response. integrated approach allows identification vulnerable subjects can be interest guide antiviral prophylaxis at an individual level.

Язык: Английский

---

Severe Tick-Borne Encephalitis (TBE) in a Patient with X-Linked Agammaglobulinemia; Treatment with TBE Virus IgG Positive Plasma, Clinical Outcome and T Cell Responses

Journal of Clinical Immunology, Год журнала: 2024, Номер 44(5)

Опубликована: Апрель 27, 2024

Abstract Purpose A patient with X-linked agammaglobulinemia (XLA) and severe tick-borne encephalitis (TBE) was treated TBE virus (TBEV) IgG positive plasma. The patient’s clinical response, humoral cellular immune responses were characterized pre- post-infection. Methods ELISA neutralisation assays performed on sera TBEV PCR assay cerebrospinal fluid. T cell conducted peripheral blood the five healthy vaccinated controls. Results admitted to hospital headache fever. He not against but receiving subcutaneous IgG-replacement therapy (IGRT). antibodies low-level (due scIGRT), IgM tests negative. During hospitalisation his condition deteriorated (Glasgow coma scale 3/15) he in ICU corticosteroids external ventricular drainage. then plasma containing without apparent side effects. His symptoms improved within a few days test converted positive. Robust CD8 + observed at three 18-months post-infection, absence of B cells. This confirmed by tetramers specific for TBEV. Conclusion IgG-positive given an XLA evident adverse reactions may have contributed outcome. Similar approaches could offer promising foundation researching therapeutic options patients immunodeficiencies. Importantly, robust response after infection despite lack cells indicates that these can clear acute viral infections benefit from future vaccination programs.

Язык: Английский

---

Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

BMC Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 10, 2024

Язык: Английский

---

T cell hybrid immunity against SARS-CoV-2 in children: a longitudinal study

EBioMedicine, Год журнала: 2024, Номер 105, С. 105203 - 105203

Опубликована: Июнь 18, 2024

Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children.

Язык: Английский

---

Improved outcome of COVID-19 over time in patients treated with CAR T-cell therapy: Update of the European COVID-19 multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP) and the European Hematology Association (EHA) Lymphoma Group

Leukemia, Год журнала: 2024, Номер 38(9), С. 1985 - 1991

Опубликована: Июль 23, 2024

Abstract COVID-19 has been associated with high mortality in patients treated Chimeric Antigen Receptor (CAR) T-cell therapy for hematologic malignancies. Here, we investigated whether the outcome improved over time primary objective of assessing COVID-19-attributable Omicron period 2022 compared to previous years. Data this multicenter study were collected using MED-A and report forms developed by EBMT. One-hundred-eighty included analysis, 39 diagnosed 2020, 35 2021 106 2022. The median age was 58.9 years (min-max: 5.2–78.4). There a successive decrease COVID-19-related (2020: 43.6%, 2021: 22.9%, 2022: 7.5%) multivariate analysis year infection strongest predictor survival ( p = 0.0001). Comparing 2020–2021, significantly fewer had lower respiratory symptoms (21.7% vs 37.8%, 0.01), needed oxygen support (25.5% 43.2%, or admitted ICU (5.7% 33.8%, Although decreased time, CAR recipients remain at higher risk complications than general population. Consequently, vigilant monitoring undergoing B-cell-targeting treatment is continuously recommended ensuring optimal prevention advanced state-of-the art when needed.

Язык: Английский

---

Effectiveness and safety of COVID-19 vaccination in people with blood cancer

European Journal of Cancer, Год журнала: 2024, Номер 201, С. 113603 - 113603

Опубликована: Фев. 5, 2024

Background People with blood cancer have increased risk of severe COVID-19 outcomes and poor response to vaccination. We assessed the safety effectiveness vaccines in this vulnerable group compared general population. Methods Individuals aged ≥12 years as 1st December 2020 QResearch primary care database were included. adjusted vaccine (aVE) against COVID-19-related hospitalisation death people using a nested matched case-control study. Using self-controlled case series methodology, we 56 pre-specified adverse events within 1-28 days first, second or third dose without cancer. Findings The cohort comprised 12,274,948 individuals, whom 81,793 had protective cancer, although they less effective, particularly hospitalisation, In population, aVE was 64% (95% confidence interval [CI] 48%-75%) 14-41 after dose, 80% CI 78%-81%) Against mortality, >80% dose. found no significant difference any between Interpretation Our study provides robust evidence which supports use vaccinations for

Язык: Английский

---