Abstract:
:Many broadly reactive human monoclonal antibodies against the hemagglutinin (HA) stem of influenza A virus have been developed for therapeutic applications. These antibodies typically inhibit viral entry steps, especially the HA conformational change that is required for membrane fusion. To better understand the mechanisms by which such antibodies inhibit viral replication, we established broadly reactive human anti-HA stem antibodies and determined the properties of these antibodies by examining their reactivity with 18 subtypes of HA, evaluating their in vivo protective efficacy, identifying their epitopes, and characterizing their inhibitory mechanisms. Among the eight human monoclonal antibodies we generated, which recognized at least 3 subtypes of the soluble HA antigens tested, clone S9-1-10/5-1 reacted with 18 subtypes of HA and protected mice from lethal infection with H1N1pdm09, H3N2, H5N1, and H7N9 viruses. This antibody recognized the HA2 helix A in the HA stem, and inhibited virus particle release from infected cells but did not block viral entry completely. These results show that broadly reactive human anti-HA stem antibodies can exhibit protective efficacy by inhibiting virus particle release. These findings expand our knowledge of the mechanisms by which broadly reactive stem-targeting antibodies inhibit viral replication and provide valuable information for universal vaccine development.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Yamayoshi S,Uraki R,Ito M,Kiso M,Nakatsu S,Yasuhara A,Oishi K,Sasaki T,Ikuta K,Kawaoka Ydoi
10.1016/j.ebiom.2017.03.007subject
Has Abstractpub_date
2017-03-01 00:00:00pages
182-191issn
2352-3964pii
S2352-3964(17)30094-4journal_volume
17pub_type
杂志文章相关文献
EBioMedicine文献大全abstract::Warming temperatures may increase the geographic spread of vector-borne diseases into temperate areas. Although a tropical mosquito-borne viral disease, a dengue outbreak occurred in Madeira, Portugal, in 2012; the first in Europe since 1920s. This outbreak emphasizes the potential for dengue re-emergence in Europe gi...
journal_title:EBioMedicine
pub_type: 历史文章,杂志文章
doi:10.1016/j.ebiom.2016.03.046
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND:Sphingomyelin synthase 1 (SMS1) has been reported to participate in hepatitis and atherosclerosis. However, its role in autoimmune response is not clear. This study investigates the possible involvement of SMS1 in B-cell activation and lupus-like autoimmunity. METHODS:SMS1 knockout lupus-like animal model a...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.06.038
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Transcriptional dysregulation drives cancer formation but the underlying mechanisms are still poorly understood. Renal cell carcinoma (RCC) is the most common malignant kidney tumor which canonically activates the hypoxia-inducible transcription factor (HIF) pathway. Despite intensive study, novel therapeuti...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.01.063
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:Preoperative prediction of lymph node (LN) status is of crucial importance for appropriate treatment planning in patients with colorectal cancer (CRC). In this study, we sought to develop and validate a non-invasive nomogram model to preoperatively predict LN metastasis in CRC. METHODS:Development of the no...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.09.052
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:The resistance to EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) is a major challenge in the treatment of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms behind resistance is therefore an important issue. Here we assessed the role of EGFR pathway substrate 8 (EPS8) and Forkhe...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.01.053
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Dachshund homologue 1 (DACH1) is highly expressed in LGR5+ intestinal stem cells and colorectal tumours. However, the roles of DACH1 in intestinal cell stemness and colorectal tumorigenesis remain largely undefined. METHODS:We used immunohistochemistry, western blotting and quantitative real-time PCR to ana...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102800
更新日期:2020-06-01 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:BACKGROUND:Anti-angiogenic treatment failure is often attributed to drug resistance, unsuccessful drug delivery, and tumor heterogeneity. Recent studies have speculated that anti-angiogenic treatments may fail due to characteristics inherent to tumor-associated blood vessels. Tumor-associated blood vessels are phenotyp...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.03.026
更新日期:2019-04-01 00:00:00
abstract:PURPOSE:We present a systematic screening for identifying associations between prescribed drugs and cancer risk using the high quality Danish nationwide health registries. METHODS:We identified all patients (cases) with incident cancer in Denmark during 2000-2012 (n=278,485) and matched each case to 10 controls. Compl...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.03.018
更新日期:2016-05-01 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:Early diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19. METHODS:In this prospective observational study, we used real-time, online, pro...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103154
更新日期:2021-01-01 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::Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely target...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.05.015
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state a...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.07.024
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Molecular subtyping of cancer aimed to predict patient overall survival (OS) and nominate drug targets for patient treatments is central to precision oncology. Owing to the rapid development of phosphoproteomics, we can now measure thousands of phosphoproteins in human cancer tissues. However, limited studie...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2018.12.039
更新日期:2019-02-01 00:00:00
abstract::Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post conc...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2018.01.021
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:The mitochondrial associated endoplasmic reticulum (ER) membrane (MAM) provides a platform for communication between the mitochondria and ER, and it plays a vital role in many biological functions. Disulphide-bond A oxidoreductase-like protein (DsbA-L), expressed in the MAM, serves as an antioxidant and redu...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.04.044
更新日期:2019-05-01 00:00:00
abstract::Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n=28) and non-O. viverrini associated (n...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2016.04.034
更新日期:2016-06-01 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:OBJECTIVE:The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA). METHODS:Seventy-five patients with GPA and a PR3-ANCA rise d...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.01.033
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Spleen tyrosine kinase (SYK) is frequently upregulated in recurrent ovarian carcinomas, for which effective therapy is urgently needed. SYK phosphorylates several substrates, but their translational implications remain unclear. Here, we show that SYK interacts with EGFR and ERBB2, and directly enhances their...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.08.055
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Liver fibrosis is a consequence of chronic inflammation and is associated with protein changes within the hepatocytes structure. In this study, we aimed to investigate if this is reflected by the urinary proteome and can be explored to diagnose liver fibrosis in patients with chronic liver disease. METHODS:...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.103083
更新日期:2020-12-01 00:00:00
abstract::Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of "pharmacometabolomics-aided pharmacogenomics" in autoimmune diseases. We envisage merging ...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2016.02.001
更新日期:2016-02-02 00:00:00
abstract:BACKGROUND:High-molecular-weight kininogen is a cofactor of the human contact system, an inflammatory response mechanism that is activated during sepsis. It has been shown that high-molecular-weight kininogen contributes to endotoxemia, but is not critical for local host defense during pneumonia by Gram-negative bacter...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2020.102908
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:The diagnosis of multidrug resistant and extensively drug resistant tuberculosis is a global health priority. Whole genome sequencing of clinical Mycobacterium tuberculosis isolates promises to circumvent the long wait times and limited scope of conventional phenotypic antimicrobial susceptibility, but gaps ...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.04.016
更新日期:2019-05-01 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: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::Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2017.03.024
更新日期:2017-04-01 00:00:00
abstract::Autophagy is a catabolic process that facilitates nutrient recycling via degradation of damaged organelles and proteins through lysosomal mediated degradation. Alterations in this complex, and tightly regulated process, lead to disease. Autophagy is widely accepted as cytoprotective against neurodegenerative diseases ...
journal_title:EBioMedicine
pub_type: 杂志文章,评审
doi:10.1016/j.ebiom.2016.10.034
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Pleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibr...
journal_title:EBioMedicine
pub_type: 杂志文章
doi:10.1016/j.ebiom.2019.02.057
更新日期:2019-03-01 00:00:00