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epitope spreading

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https://www.readbyqxmd.com/read/28231271/applying-antibody-sensitive-hypervariable-region-1-deleted-hepatitis-c-virus-to-the-study-of-escape-pathways-of-neutralizing-human-monoclonal-antibody-ar5a
#1
Rodrigo Velázquez-Moctezuma, Mansun Law, Jens Bukh, Jannick Prentoe
Hepatitis C virus (HCV) is a major cause of end-stage liver diseases. With 3-4 million new HCV infections yearly, a vaccine is urgently needed. A better understanding of virus escape from neutralizing antibodies and their corresponding epitopes are important for this effort. However, for viral isolates with high antibody resistance, or antibodies with moderate potency, it remains challenging to induce escape mutations in vitro. Here, as proof-of-concept, we used antibody-sensitive HVR1-deleted (ΔHVR1) viruses to generate escape mutants for a human monoclonal antibody, AR5A, targeting a rare cross-genotype conserved epitope...
February 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28198446/a-mutation-identified-in-neonatal-microcephaly-destabilizes-zika-virus-ns1-assembly-in-vitro
#2
Deping Wang, Cheng Chen, Shengnan Liu, Han Zhou, Kailin Yang, Qi Zhao, Xiaoyun Ji, Chen Chen, Wei Xie, Zefang Wang, Li-Zhi Mi, Haitao Yang
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193250/a-novel-modified-indirect-elisa-based-on-spherical-body-protein-4-for-detecting-antibody-during-acute-and-long-term-infections-with-diverse-babesia-bovis-strains
#3
Chungwon J Chung, Carlos E Suarez, Carey L Bandaranayaka-Mudiyanselage, Chandima-Bandara Bandaranayaka-Mudiyanselage, Joanna Rzepka, T J Heiniger, Grace Chung, Stephen S Lee, Ethan Adams, Grace Yun, Susan J Waldron
BACKGROUND: Cattle persistently infected with Babesia bovis are reservoirs for intra- and inter-herd transmission. Since B. bovis is considered a persistent infection, developing a reliable, high-throughput assay that detects antibody during all stages of the infection could be pivotal for establishing better control protocols. METHODS: A modified indirect enzyme-linked immunosorbent assay (MI-ELISA) was developed using the spherical body protein-4 (SBP4) of B. bovis to detect antibody against diverse strains through all infection stages in cattle...
February 13, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28188693/two-distinct-genotypes-of-porcine-epidemic-diarrhoea-virus-in-vaccinated-pig-flocks-in-shandong-province-of-china-2012-2015
#4
Y Zhang, Y Tian, S-L Lin, S-F Sun, J Chen, G-S Wang, F-L Tian, S-J Jiang
As one of the top pork producers in China, Shandong Province suffered frequent outbreaks of porcine epidemic diarrhoea virus (PEDV) on pig farms from January 2012 to July 2015, resulting in significant economic losses. To better understand the prevalence situation, we conducted molecular epidemiological analyses of 38 PEDV strains isolated from 13 cities in Shandong Province. The detection rate of PEDV was 71.2% (146/205) by reverse transcription polymerase chain reaction (RT-PCR). The S genes of the 38 isolated samples were 4146 to 4161 nt in length and shared high levels of sequence identity (93...
February 10, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28152559/t-cell-responses-to-peptides-of-goodpasture-autoantigen-in-patients-with-anti-glomerular-basement-membrane-disease
#5
Shui-Yi Hu, Xiao-Yu Jia, Qiu-Hua Gu, Chong-Yan Yu, Xu-Yang Cheng, Qi-Zhuang Jin, Fu-de Zhou, Zhao Cui, Ming-Hui Zhao
AIM: Cell-mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti-glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti-GBM patients, aiming to identify the epitopes and their clinical significance. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti-GBM disease. Twenty-four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1...
February 2, 2017: Nephrology
https://www.readbyqxmd.com/read/28101965/a-multi-hit-hypothesis-of-bullous-pemphigoid-and-associated-neurological-disease-is-hla-dqb1-03-01-a-potential-link-between-immune-privileged-antigen-exposure-and-epitope-spreading
#6
REVIEW
K T Amber, J Zikry, M Hertl
Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of HLA-DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease...
January 19, 2017: HLA
https://www.readbyqxmd.com/read/28024362/controlled-sub-nanometer-epitope-spacing-in-a-three-dimensional-self-assembled-peptide-hydrogel
#7
E Thomas Pashuck, Benoît J R Duchet, Catherine S Hansel, Stephanie A Maynard, Lesley W Chow, Molly M Stevens
Cells in the body use a variety of mechanisms to ensure the specificity and efficacy of signal transduction. One way that this is achieved is through tight spatial control over the position of different proteins, signaling sequences, and biomolecules within and around cells. For instance, the extracellular matrix protein fibronectin presents RGDS and PHSRN sequences that synergistically bind the α5β1 integrin when separated by 3.2 nm but are unable to bind when this distance is >5.5 nm.1 Building biomaterials to controllably space different epitopes with subnanometer accuracy in a three-dimensional (3D) hydrogel is challenging...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/27965307/dual-specific-chimeric-antigen-receptor-t-cells-and-an-indirect-vaccine-eradicate-a-variety-of-large-solid-tumors-in-an-immunocompetent-self-antigen-setting
#8
Clare Y Slaney, Bianca von Scheidt, Alexander J Davenport, Paul Beavis, Jennifer A Westwood, Sherly Mardiana, David Tscharke, Sarah Ellis, H Miles Prince, Joseph A Trapani, Ricky W Johnstone, Mark J Smyth, Michele W L Teng, Aesha Ali, Zhiya Yu, Steven A Rosenberg, Nicholas P Restifo, Paul J Neeson, Phillip K Darcy, Michael H Kershaw
PURPOSE: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. EXPERIMENTAL DESIGN: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100)...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27923570/recombinant-dna-vaccine-of-hantavirus-gn-and-lamp1-induced-long-term-immune-protection-in-mice
#9
Dong-Bo Jiang, Li-Juan Sun, Lin-Feng Cheng, Jin-Peng Zhang, Shao-Bo Xiao, Yuan-Jie Sun, Shu-Ya Yang, Jing Wang, Fang-Lin Zhang, Kun Yang
BACKGROUND: Prophylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations. METHODS & RESULTS: Immune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27891225/unraveling-the-role-of-preexisting-immunity-in-prostate-cancer-patients-vaccinated-with-a-her-2-neu-hybrid-peptide
#10
Ioannis F Voutsas, Eleftheria A Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27860539/epitope-specific-antitumor-immunity-suppresses-tumor-spread-in-papillary-thyroid-cancer
#11
Margret Ehlers, Anne Kuebart, Hubertus Hautzel, Juergen Enczmann, Anna-Carinna Reis, Matthias Haase, Stephanie Allelein, Till Dringenberg, Christine Schmid, Matthias Schott
CONTEXT: Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome. OBJECTIVE: Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome. PATIENTS: 150 PTC patients; 40 Hashimoto's thyroiditis (HT) patients; 21 healthy controls; 27.239 healthy Caucasians (for HLA typing). MAIN OUTCOME MEASURES: HLA class I restricted thyroperoxidase (TPO) and thyroglobulin (Tg) epitope-specific T cells (tetramer analyses), correlation analyses between HLA class II phenotypes, T cell immunity, and the clinical course...
November 18, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27835913/circulation-autoantibody-against-lamin-a-c-in-patients-with-sj%C3%A3-gren-s-syndrome
#12
Wen Zhang, Chunyan Zhang, Peng Chen, Chunhe Yang, Xianfeng Gan, Muhammad Hussain, Yiping Xun, Yaping Tian, Hongwu Du
Lamin A/C proteins are major components of nuclear laminae and were encoded by the LMNA gene. Recent studies have found that in addition to provides nuclear-membrane strength; it also regulates the gene expression. Lamin A/C has been confirmed as an autoantigen in RA, SLE and vasculitis. Anti-Lamin A/C antibodies also have been found by indirect immunofluorescence method. In this study, we used various research methods to confirm Lamin A/C is an autoantigen in Han Chinese patients with confirmed Sjögren's syndrome (SS)...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834908/epitope-identification-and-application-for-diagnosis-of-duck-tembusu-virus-infections-in-ducks
#13
Chenxi Li, Junyan Liu, Wulin Shaozhou, Xiaofei Bai, Qingshan Zhang, Ronghong Hua, Jyung-Hurng Liu, Ming Liu, Yun Zhang
Duck Tembusu virus (DTMUV) causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein using the non-neutralizing monoclonal antibodies (mAbs) 1F3 and 1A5. Two minimal epitopes were mapped to (221)LD/NLPW(225) and (87)YAEYI(91) by using phage display and mutagenesis. DTMUV-positive duck sera reacted with the epitopes, thus indicating the importance of the minimal amino acids of the epitopes for antibody-epitope binding...
November 10, 2016: Viruses
https://www.readbyqxmd.com/read/27821747/systematic-autoantigen-analysis-identifies-a-distinct-subtype-of-scleroderma-with-coincident-cancer
#14
George J Xu, Ami A Shah, Mamie Z Li, Qikai Xu, Antony Rosen, Livia Casciola-Rosen, Stephen J Elledge
Scleroderma is a chronic autoimmune rheumatic disease associated with widespread tissue fibrosis and vasculopathy. Approximately two-thirds of all patients with scleroderma present with three dominant autoantibody subsets. Here, we used a pair of complementary high-throughput methods for antibody epitope discovery to examine patients with scleroderma with or without known autoantibody specificities. We identified a specificity for the minor spliceosome complex containing RNA Binding Region (RNP1, RNA recognition motif) Containing 3 (RNPC3) that is found in patients with scleroderma without known specificities and is absent in unrelated autoimmune diseases...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27795425/recombinant-receptor-binding-domains-of-multiple-middle-east-respiratory-syndrome-coronaviruses-mers-covs-induce-cross-neutralizing-antibodies-against-divergent-human-and-camel-mers-covs-and-antibody-escape-mutants
#15
Wanbo Tai, Yufei Wang, Craig A Fett, Guangyu Zhao, Fang Li, Stanley Perlman, Shibo Jiang, Yusen Zhou, Lanying Du
: Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27783408/update-on-shigella-new-serogroups-serotypes-and-their-antimicrobial-resistance
#16
REVIEW
D P Muthuirulandi Sethuvel, N K Devanga Ragupathi, S Anandan, B Veeraraghavan
Shigellosis represents a major burden of disease in developing countries. A low infectious dose allows the disease to be spread effectively. Although shigellosis is mostly a self-limiting disease, antibiotics are recommended to reduce deaths, disease symptoms and organism-shedding time. However, in India, antimicrobial resistance among the genus Shigella is more common than among any other enteric bacteria. Notably, new serotypes or subserotypes in Shigella are reported from various parts of the world. Identification of new subserotypes of Shigella spp...
January 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/27760308/evaluation-of-a-synthetic-peptide-from-the-taenia-saginata-18kda-surface-secreted-oncospheral-adhesion-protein-for-serological-diagnosis-of-bovine-cysticercosis
#17
Rafaella Paola Meneguete Guimarães-Peixoto, Paulo Sérgio Arruda Pinto, Marcus Rebouças Santos, Marcelo Depólo Polêto, Letícia Ferreira Silva, Abelardo Silva-Júnior
Bovine cysticercosis is a zoonotic infection widely spread throughout Brazil, creating a burden on hygiene maintenance and the economy. Diagnosis of cysticercosis usually relies on post mortem inspection of carcasses in slaughterhouses. This detection method provides only low sensitivity. Recent advancements have improved the performance of serologic tests, such as ELISA, providing greater sensitivity and specificity. The objective of the current study was to identify and evaluate a synthetic peptide derived from the Taenia saginata 18kDa oncospheric surface protein for the diagnosis of bovine cysticercosis in ELISA...
December 2016: Acta Tropica
https://www.readbyqxmd.com/read/27743643/nodo-paranodopathy-internodopathy-and-cleftopathy-target-based-reclassification-of-guillain-barr%C3%A3-like-immune-mediated-polyradiculoneuropathies-in-dogs-and-cats
#18
Simone Gross, Andrea Fischer, Marco Rosati, Lara Matiasek, Daniele Corlazzoli, Rodolfo Cappello, Laura Porcarelli, Tom Harcourt-Brown, Konrad Jurina, Laurent Garosi, Thomas Flegel, Pia Quitt, Jessica Molin, Velia-Isabel Huelsmeyer, Henning Schenk, Gualtiero Gandini, Kirsten Gnirs, Stéphane Blot, Aurélien Jeandel, Massimo Baroni, Shenja Loderstedt, Gianluca Abbiati, Carola Leithaeuser, Sabine Schulze, Marion Kornberg, Mark Lowrie, Kaspar Matiasek
Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of routine work-up in human patients we evaluated tissues taken from companion animals affected by GBS-like polyradiculoneuropathy to screen for distribution of immune cells, targeted fibre components and segregating non-inflammatory lesions...
December 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27736723/biofunctionalized-peptide-based-hydrogels-provide-permissive-scaffolds-to-attract-neurite-outgrowth-from-spiral-ganglion-neurons
#19
Claudia Frick, Marcus Müller, Ute Wank, Anke Tropitzsch, Benedikt Kramer, Pascal Senn, Helge Rask-Andersen, Karl-Heinz Wiesmüller, Hubert Löwenheim
Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI...
January 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27713074/an-influenza-a-virus-h7n9-anti-neuraminidase-monoclonal-antibody-with-prophylactic-and-therapeutic-activity-in%C3%A2-vivo
#20
Jason R Wilson, Zhu Guo, Adrian Reber, Ram P Kamal, Nedzad Music, Shane Gansebom, Yaohui Bai, Min Levine, Paul Carney, Wen-Pin Tzeng, James Stevens, Ian A York
Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. Treatment options for people infected with A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other influenza viruses, A(H7N9) can become resistant to these drugs. The use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed against the NA of A(H7N9) and show that prophylactic systemic administration of 3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013 (H7N9)...
October 3, 2016: Antiviral Research
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