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Neutralizing antibodies

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https://www.readbyqxmd.com/read/28549109/il-18-cleavage-triggers-cardiac-inflammation-and-fibrosis-upon-%C3%AE-adrenergic-insult
#1
Han Xiao, Hao Li, Jing-Jing Wang, Jian-Shu Zhang, Jing Shen, Xiang-Bo An, Cong-Cong Zhang, Ji-Min Wu, Yao Song, Xin-Yu Wang, Hai-Yi Yu, Xiang-Ning Deng, Zi-Jian Li, Ming Xu, Zhi-Zhen Lu, Jie Du, Wei Gao, Ai-Hua Zhang, Yue Feng, You-Yi Zhang
Aims: Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult. Methods and results: Male C57BL/6 mice were injected with a single dose of β-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously...
May 26, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28548638/asymmetric-recognition-of-hiv-1-envelope-trimer-by-v1v2-loop-targeting-antibodies
#2
Haoqing Wang, Harry B Gristick, Louise Scharf, Anthony P West, Rachel P Galimidi, Michael S Seaman, Natalia T Freund, Michel C Nussenzweig, Pamela J Bjorkman
The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3...
May 26, 2017: ELife
https://www.readbyqxmd.com/read/28548626/correlates-of-protection-for-inactivated-enterovirus-71-vaccine-the-analysis-of-immunological-surrogate-endpoints
#3
Wenbo Zhu, Pengfei Jin, Jing-Xin Li, Feng-Cai Zhu, Pei Liu
BACKGROUND: Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. METHOD: Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine...
May 26, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28548091/cellular-interplay-via-cytokine-hierarchy-causes-pathological-cardiac-hypertrophy-in-raf1-mutant-noonan-syndrome
#4
Jiani C Yin, Mathew J Platt, Xixi Tian, Xue Wu, Peter H Backx, Jeremy A Simpson, Toshiyuki Araki, Benjamin G Neel
Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1(L613V/+) knock-in mice. Here, using inducible Raf1(L613V) expression, we show that LVH results from the interplay of cardiac cell types. Cardiomyocyte Raf1(L613V) enhances Ca(2+) sensitivity and cardiac contractility without causing hypertrophy...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#5
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28544312/c-x-c-motif-chemokine-receptor-4-promotes-tumor-angiogenesis-in-gastric-cancer-via-activation-of-jak2-stat3
#6
Qing Zhang, Feng Xu, Yi Shi, Yi-Wen Chen, Hai-Ping Wang, Xue Yu, Yong Li
C-X-C motif chemokine receptor 4 (CXCR4) overexpression promotes gastric cancer growth and metastasis. In this study, we determined its role in regulating tumor angiogenesis. We overexpressed CXCR4 in gastric cancer cells and examined the effects of conditioned medium on endothelial cell proliferation, migration, and tube formation. The effects of CXCR4 overexpression on vascular endothelial growth factor (VEGF) expression and signal transducer and activator of transcription 3 (STAT3) activation were analyzed...
May 24, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28543534/a-chimeric-protein-of-cfa-i-cs6-subunits-and-ltb-sta-toxoid-could-protect-immunized-mice-against-enterotoxigenic-escherichia-coli
#7
Narges Zeinalzadeh, Ali Hatef Salmanian, Goli Goujani, Jafar Amani, Ghasem Ahangari, Asal Akhavian, Mahyat Jafari
Enterotoxigenic Escherichia Coli (ETEC) strains are the most common bacteria causing diarrhea in children in developing countries and travelers to these areas. Colonization factors (CFs) and enterotoxins are the main virulence determinants in ETEC pathogenesis. Heterogeneity of CFs commonly considered as the bottleneck to achieve an effective vaccine. On the other hand, it is believed that a broad spectrum protection against ETEC would be available when the anti-CF and anti-enterotoxin immunity were induced simultaneously...
May 23, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28542611/no-molecular-or-serological-evidence-of-zikavirus-infection-among-healthy-blood-donors-living-in-or-travelling-to-regions-where-aedes-albopictus-circulates
#8
Wegene Borena, Tamara Hofer, Karin Stiasny, Stephan W Aberle, Manfred Gaber, Dorothee von Laer, Harald Schennach
BACKGROUND: Previous studies have shown that Zika virus can infect and be transmitted by A. albopictus. The World Health organization (WHO) has raised concerns of autochthonous transmission of the virus in regions where the vector is endemic. The aim of this pilot study was to assess the occurrence of Zika virus (ZIKV) in western Austria (Tyrol) especially after a history of travel to A. albopictus endemic regions. METHODS: The study participants were healthy blood donors at randomly selected donation sites in the west Austrian region Tyrol...
2017: PloS One
https://www.readbyqxmd.com/read/28542577/leptin-signals-via-tgfb1-to-promote-metastatic-potential-and-stemness-in-breast-cancer
#9
Ameet K Mishra, Christopher R Parish, Ma-Li Wong, Julio Licinio, Anneke C Blackburn
Epidemiological studies have shown obesity to be linked with poorer outcomes in breast cancer patients. The molecular mechanisms responsible for the increased risk of invasive/metastatic disease with obesity are complex, but may include elevated levels of adipokines such as leptin. Using physiological levels of leptin found in obesity in a novel chronic in vitro treatment model (≤200 ng/ml for 14 days), we confirmed the occurrence of leptin-mediated changes in growth, apoptosis and metastatic behavior, and gene expression changes representing epithelial-to-mesenchymal transition (EMT) and a cancer stem cell (CSC) like phenotype in breast epithelial and cancer cell lines (MCF10A, MCF10AT1, MCF7 and MDA-MB-231)...
2017: PloS One
https://www.readbyqxmd.com/read/28542556/an-inactivated-hand-foot-and-mouth-disease-vaccine-using-the-enterovirus-71-c4a-strain-isolated-from-a-korean-patient-induces-a-strong-immunogenic-response-in-mice
#10
Hyun Ju In, Heeji Lim, Jung-Ah Lee, Hye Jin Kim, Jin-Won Kim, Ji-Yeon Hyeon, Sang-Gu Yeo, June-Woo Lee, Jung Sik Yoo, Young Ki Choi, Sang-Won Lee
Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later...
2017: PloS One
https://www.readbyqxmd.com/read/28542361/granulocyte-colony-stimulating-factor-blockade-enables-dexamethasone-to-inhibit-lipopolysaccharide-induced-murine-lung-neutrophils
#11
Jesus Banuelos, Yun Cao, Soon Cheon Shin, Bruce S Bochner, Pedro Avila, Shihong Li, Xin Jiang, Mark W Lingen, Robert P Schleimer, Nick Z Lu
Glucocorticoids promote neutrophilic inflammation, the mechanisms of which are poorly characterized. Using a lipopolysaccharide (LPS)-induced acute murine lung injury model, we determined the role of granulocyte colony-stimulating factor (G-CSF) in mouse lung neutrophil numbers in the absence and presence of dexamethasone, a potent glucocorticoid. G-CSF was blocked using a neutralizing antibody. Airway neutrophil numbers, cytokine levels, and lung injury parameters were measured. Glucocorticoid treatment maintained LPS-induced airway G-CSF while suppressing TNF and IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/28542275/combination-of-the-immunization-with-the-sequence-close-to-the-consensus-sequence-and-two-dna-prime-plus-one-vlp-boost-generate-h5-hemagglutinin-specific-broad-neutralizing-antibodies
#12
Guiqin Wang, Renfu Yin, Paul Zhou, Zhuang Ding
Hemagglutinin (HA) head has long been considered to be able to elicit only a narrow, strain-specific antibody response as it undergoes rapid antigenic drift. However, we previously showed that a heterologous prime-boost strategy, in which mice were primed twice with DNA encoding HA and boosted once with virus-like particles (VLP) from an H5N1 strain A/Thailand/1(KAN)-1/2004 (noted as TH DDV), induced anti-head broad cross-H5 neutralizing antibody response. To explain why TH DDV immunization could generate such breadth, we systemically compared the neutralization breadth and potency between TH DDV sera and immune sera elicited by TH DDD (three times of DNA immunizations), TH VVV (three times of VLP immunizations), TH DV (one DNA prime plus one VLP boost) and TK DDV (plasmid DNA and VLP derived from another H5N1 strain, A/Turkey/65596/2006)...
2017: PloS One
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#13
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs), but can also expose binding sites for some types of non-neutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539448/virological-control-by-the-cd4-binding-site-antibody-n6-in-shiv-infected-rhesus-monkeys
#14
Boris Julg, Amarendra Pegu, Peter Abbink, Jinyan Liu, Amanda Brinkman, Katherine Molloy, Shanell Mojta, Abishek Chandrashekar, Katherine Callow, Keyun Wang, Xuejun Chen, Stephen D Schmidt, Jinghe Huang, Richard A Koup, Michael S Seaman, Brandon F Keele, John R Mascola, Mark Connors, Dan H Barouch
Passive immunotherapies against HIV-1 will most likely require broadly neutralizing antibodies (bnAb) with maximum breadth and potency to assure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross clade pseudoviruses. We evaluated the in-vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically SHIV-SF162P3 infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7 (mean 1...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539445/structure-of-simian-immunodeficiency-virus-envelope-spikes-bound-with-cd4-and-monoclonal-antibody-36d5
#15
Guiqing Hu, Jun Liu, Kenneth H Roux, Kenneth A Taylor
The HIV-1/SIV envelope spike (Env) mediates the viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the co-receptor binding site and is a target for neutralizing antibodies. We have used cryoelectron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody 36D5 to gp120 of the SIV Env. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest the antibody exerts its neutralization effect by blocking the co-receptor binding site...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539444/improved-prefusion-stability-optimized-codon-usage-and-augmented-virion-packaging-enhance-the-immunogenicity-of-respiratory-syncytial-virus-rsv-fusion-protein-in-a-vectored-vaccine-candidate
#16
Bo Liang, Joan O Ngwuta, Sonja Surman, Barbora Kabatova, Xiang Liu, Matthias Lingemann, Xueqiao Liu, Lijuan Yang, Richard Herbert, Joanna Swerczek, Man Chen, Syed M Moin, Azad Kumar, Jason S McLellan, Peter D Kwong, Barney S Graham, Peter L Collins, Shirin Munir
Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory tract disease worldwide, but lacks a licensed vaccine or suitable antiviral drug. A live-attenuated chimeric bovine/human parainfluenza virus type-3 (rB/HPIV3) was developed previously as a vector expressing RSV fusion (F) protein to confer bivalent protection against RSV and HPIV3. In a previous clinical trial in virus-naïve children, rB/HPIV3 was well-tolerated but the immunogenicity of wildtype RSV F was unsatisfactory...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28539438/discovery-of-a-prefusion-rsv-f-specific-monoclonal-antibody-that-provides-greater-in-vivo-protection-than-the-murine-precursor-of-palivizumab
#17
Min Zhao, Zi-Zheng Zheng, Man Chen, Kayvon Modjarrad, Wei Zhang, Lu-Ting Zhan, Jian-Li Cao, Yong-Peng Sun, Jason S McLellan, Barney S Graham, Ning-Shao Xia
Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the RSV F glycoprotein, is the only prophylactic agent approved for RSV. However, its relatively low neutralizing potency and high cost has limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F trimer...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538175/extracellular-vesicles-from-a-helminth-parasite-suppress-macrophage-activation-and-constitute-an-effective-vaccine-for-protective-immunity
#18
Gillian Coakley, Jana L McCaskill, Jessica G Borger, Fabio Simbari, Elaine Robertson, Marissa Millar, Yvonne Harcus, Henry J McSorley, Rick M Maizels, Amy H Buck
Recent studies have demonstrated that many parasites release extracellular vesicles (EVs), yet little is known about the specific interactions of EVs with immune cells or their functions during infection. We show that EVs secreted by the gastrointestinal nematode Heligmosomoides polygyrus are internalized by macrophages and modulate their activation. EV internalization causes downregulation of type 1 and type 2 immune-response-associated molecules (IL-6 and TNF, and Ym1 and RELMα) and inhibits expression of the IL-33 receptor subunit ST2...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28536429/a-novel-neutralizing-monoclonal-antibody-targeting-the-n-terminal-domain-of-the-mers-cov-spike-protein
#19
Yingzhu Chen, Shuai Lu, Hao Jia, Yao Deng, Jianfang Zhou, Baoying Huang, Yueyang Yu, Jiaming Lan, Wenling Wang, Yongliang Lou, Kun Qin, Wenjie Tan
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused fatal infections, some through hospital-acquired transmission, in affected regions since its emergence in 2012. Although the virus is not pandemic among humans, it poses a great threat to public health due to its zoonotic origin. Thus, both preventative and therapeutic countermeasures are urgently needed. In this study, we discovered a panel of neutralizing monoclonal antibodies (mAbs) against MERS-CoV, which mapped to a wide range of regions on the spike (S) protein of the virus...
May 24, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28536308/immune-correlates-of-gm-csf-and-melanoma-peptide-vaccination-in-a-randomized-trial-for-the-adjuvant-therapy-of-resected-high-risk-melanoma-e4697
#20
Lisa H Butterfield, Fengmin Zhao, Sandra Lee, Ahmad A Tarhini, Kim A Margolin, Richard L White, Michael Atkins, Gary I Cohen, Theresa L Whiteside, John M Kirkwood, David H Lawson
Purpose: E4697 was a multi-center intergroup randomized placebo-controlled Phase III trial of adjuvant GM-CSF and/or a multi-epitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma. <p>Experimental Design: 815 patients were enrolled from 12/99 to 10/06 into this 6-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in Montanide was designed to promote melanoma specific CD8(+) T cell responses...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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