Abstract:
BACKGROUND:T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults. METHODS:We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18-46years and 24 subjects aged 50years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18months. FINDINGS:Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP+M1 vaccination was significantly higher compared to ChAdOx1 NP+M1. In a mixed regression model, T-cell responses over 18months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP+M1. INTERPRETATION:A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP+M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A. FUNDING SOURCE:Medical Research Council UK, NIHR BMRC Oxford.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Coughlan L,Sridhar S,Payne R,Edmans M,Milicic A,Venkatraman N,Lugonja B,Clifton L,Qi C,Folegatti PM,Lawrie AM,Roberts R,de Graaf H,Sukhtankar P,Faust SN,Lewis DJM,Lambe T,Hill A,Gilbert SCdoi
10.1016/j.ebiom.2018.02.011subject
Has Abstractpub_date
2018-03-01 00:00:00pages
146-154issn
2352-3964pii
S2352-3964(18)30065-3journal_volume
29pub_type
杂志文章相关文献
EBioMedicine文献大全abstract:BACKGROUND:We developed and validated an artificial intelligence (AI)-assisted prediction of preeclampsia applied to a nationwide health insurance dataset in Indonesia. METHODS:The BPJS Kesehatan dataset have been preprocessed using a nested case-control design into preeclampsia/eclampsia (n = 3318) and normotensive p...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102710
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Neurodegenerative diseases are incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in photoreceptor death and progresses to the loss of the entire retinal network. We previously found that proteomic analysis of the adja...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102636
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103129
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. METHODS:To evaluate the impact of ATRX loss of function (LoF) in neuroblastoma, we utilized CRISPR-Ca...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102971
更新日期:2020-09-01 00:00:00
abstract::Sickle cell anaemia (SCA) results from a single mutation in the β globin gene. It is seldom symptomatic in the first semester of life. We analysed the expression pattern of 9 adhesion molecules on red blood cells, in a cohort of 54 SCA and 17 non-SCA very young infants of comparable age (median 144 days, 81-196). Haem...
journal_title:EBioMedicine
pub_type: 临床试验,杂志文章
doi:10.1016/j.ebiom.2014.12.006
更新日期:2014-12-18 00:00:00
abstract:OBJECTIVE:The phase III clinical trial PERFECT was designed to assess clinical safety and efficacy of intramyocardial CD133+ bone marrow stem cell treatment combined with CABG for induction of cardiac repair. DESIGN:Multicentre, double-blinded, randomised placebo controlled trial. SETTING:The study was conducted acro...
journal_title:EBioMedicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.ebiom.2017.07.022
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:A phase II study of methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) sandwiched with radiotherapy for newly diagnosed, stage IE-IIE extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL) was conducted to explore its clinical efficacy and safety, as well as novel serum biomarkers upon an...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.10.011
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:Salmonella causes intracellular infections in humans. Besides quinolones, third generation cephalosporins are first line drugs used for salmonellosis therapy. An unresolved anomaly of this practice involves high relapse rates associated to quinolone- or cephalosporin-susceptible Salmonella isolates in patien...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102771
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND:Some interstitial lung disease (ILD) patients develop a progressive fibrosing-ILD phenotype (PF-ILD), with similar persistent lung function decline suggesting common molecular pathways involved. Nintedanib, a tyrosine kinase inhibitor targeting the PDGF, FGF, VEGF and M-CSF pathways, has shown comparable eff...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.050
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Recurrent mutations in the promoter of the telomerase reverse transcriptase (TERT) gene (C228T and C250T) detected in tumours and cells shed into urine of urothelial cancer (UC) patients are putative biomarkers for UC detection and monitoring. However, the possibility of detecting these mutations in cell-fre...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.05.004
更新日期:2019-06-01 00:00:00
abstract::Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiolog...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.05.035
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Intervertebral disc degeneration (IDD) is a major contributor to lower back pain, however, the molecular and pathogenetic mechanisms underlying IDD are poorly understood. As a high-risk factor for IDD, compression stress was reported to induce apoptosis of nucleus pulposus (NP) cells and extracellular matrix...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102679
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:Active immunotherapy is an effective, long-lasting, cheap, and safe approach to suppress cancer progression; however, the key issue is to develop appropriate tumour vaccines. Oncoproteins are up-regulated under various stress conditions and promote cell survival. Oncoproteins and their immunogenic domains co...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.025
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Urinary tract infections are known to be caused by bacteria, but the potential implications of archaea have never been studied in this context. METHODS:In two different university hospital centres we used specific laboratory methods for the detection and culture of archaeal methanogens in 383 urine specimen...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.04.037
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Half of muscle-invasive bladder cancer patients will relapse with metastatic disease and molecular tests to predict relapse are needed. TP63 has been proposed as a prognostic biomarker in bladder cancer, but reports associating it with clinical outcomes are conflicting. Since TP63 is expressed as multiple is...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.11.022
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The development of an effective vaccine preventing HIV-1 infection is hindered by the enormous antigenic variability and unique biochemical and immunological properties of HIV-1 Env glycoprotein, the most promising target for HIV-1 neutralizing antibody. Functional studies of rare elite neutralizers led to t...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.07.015
更新日期:2019-09-01 00:00:00
abstract::A small subset of HIV-1 infected individuals, the "Elite Controllers" (EC), can control viral replication and restrain progression to immunodeficiency without antiretroviral therapy (ART). In this study, a cross-sectional transcriptomics and targeted proteomics analysis were performed in a well-defined Swedish cohort ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.11.031
更新日期:2018-01-01 00:00:00
abstract::Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen producti...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.07.019
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Atherosclerosis is a hyperlipidemia-induced condition affecting the arterial wall that damages healthy endothelial cell (EC) function, leading to enhanced risk of atherothrombotic events. Certain microRNAs regulate EC dysfunction in response to hyperlipidemia and may be suitable therapeutic targets to combat...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.01.032
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Recurrent implantation failure (RIF) remains a critical and challenging problem in assisted reproductive technology mainly due to impaired decidualization. The endocytic and transcytotic activity in the endometrium are crucial for decidualization. The most representative endocytic gene is the C-terminal Eps1...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.018
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Angiogenesis improves reperfusion to the ischaemic tissue after vascular obstruction. The underlying molecular mechanisms of post-ischaemic angiogenesis are not clear. FAM3A belongs to the family with sequence similarity 3 (FAM3) genes, but its biological function in endothelial cells in regards to vascular ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.038
更新日期:2019-05-01 00:00:00
abstract::Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and v...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2015.08.026
更新日期:2015-08-15 00:00:00
abstract::This study aimed to develop and validate a prognostic nomogram for recurrence-free survival (RFS) after surgery in the absence of adjuvant therapy to guide the selection for adjuvant imatinib therapy based on Residual Neural Network (ResNet). The ResNet model was developed based on contrast-enhanced computed tomograph...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.12.028
更新日期:2019-01-01 00:00:00
abstract::The identification of SYK as a molecular target in B-lineage leukemia/lymphoma cells prompted the development of SYK inhibitors as a new class of anti-cancer drug candidates. Here we report that induction of the SYK gene expression in human cells causes a significant down-regulation of evolutionarily conserved genes a...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2014.10.019
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:Psoriasis is a common chronic inflammatory skin disease which lacks effective strategies for the treatment. Natural compounds with biological activities are good tools to identify new targets with therapeutic potentials. Acetyl-11-keto-β-boswellic acid (AKBA) is the most bioactive ingredient of boswellic aci...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.12.036
更新日期:2019-01-01 00:00:00
abstract::Therapeutic approaches to fight Alzheimer's disease include anti-Amyloidβ (Aβ) antibodies and secretase inhibitors. However, the blood-brain barrier (BBB) limits the brain exposure of biologics and the chemical space for small molecules to be BBB permeable. The Brain Shuttle (BS) technology is capable of shuttling lar...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.09.004
更新日期:2017-10-01 00:00:00
abstract::Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activa...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.10.008
更新日期:2016-11-01 00:00:00
abstract::Dedifferentiation of follicular cells is a central event in resistance to radioactive iodine and patient mortality in papillary thyroid carcinoma (PTC). We reveal that platelet derived growth factor receptor alpha (PDGFRα) specifically drives dedifferentiation in PTC by disrupting the transcriptional activity of thyro...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.09.007
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg "window stage", active immunization against hepatitis B virus (HBV) migh...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.10.043
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Abnormalities in membrane excitability and Na(+) channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na(+) channel blocker and membrane stabiliser flecainide in ALS. METHODS:A double-blind, placebo-cont...
journal_title:EBioMedicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.ebiom.2015.11.022
更新日期:2015-12-01 00:00:00