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https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#1
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28804489/normalized-synergy-predicts-that-cd8-co-receptor-contribution-to-t-cell-receptor-tcr-and-pmhc-binding-decreases-as-tcr-affinity-increases-in-human-viral-specific-t-cells
#2
Chad M Williams, Alexandra A Schonnesen, Shu-Qi Zhang, Ke-Yue Ma, Chenfeng He, Tori Yamamoto, S Gail Eckhardt, Christopher A Klebanoff, Ning Jiang
The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8(+) T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28803517/evaluation-of-16-commercial-antibody-elisas-for-the-detection-of-bovine-viral-diarrhea-virus-specific-antibodies-in-serum-and-milk-using-well-characterized-sample-panels
#3
Jean-Baptiste Hanon, Miet De Baere, Camille De la Ferté, Sophie Roelandt, Yves Van der Stede, Brigitte Cay
We performed a thorough fit-for-purpose evaluation of commercial ELISAs for the detection of bovine viral diarrhea virus (BVDV)-specific antibodies in serum and in milk by testing 2 panels of well-characterized serum and milk samples. Sixteen ELISAs from 9 different manufacturers, available on the Belgian market at the time of our study, were assessed for their diagnostic and analytical sensitivity (DSe and ASe, respectively), diagnostic specificity (DSp), and repeatability relative to the virus neutralization (VN) test considered to be the gold standard assay...
August 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28797733/propagation-of-respiratory-viruses-in-human-airway-epithelia-reveals-persistent-virus-specific-signatures
#4
Manel Essaidi-Laziosi, Francisco Brito, Sacha Benaoudia, Léna Royston, Valeria Cagno, Mélanie Fernandes-Rocha, Isabelle Piuz, Evgeny Zdobnov, Song Huang, Samuel Constant, Marc-Olivier Boldi, Laurent Kaiser, Caroline Tapparel
BACKGROUND: Leading etiologies of acute illnesses, respiratory viruses typically cause self-limited diseases, though severe complications can occur in fragile patients. Rhinoviruses, respiratory enteroviruses, influenza virus, respiratory syncytial viruses and coronaviruses are highly prevalent respiratory pathogens, but due to the lack of reliable animal models, their differential pathogenesis remains poorly characterized. OBJECTIVE: To compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia...
August 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28797306/seroprevalence-of-influenza-a-and-b-viruses-among-unvaccinated-children-in-the-united-arab-emirates-a-cross-sectional-study
#5
Ahmed R Alsuwaidi, Lolowa A Al-Mekaini, Salwa M Kamal, Hassib Narchi, Abdul-Kader Souid
BACKGROUND: Young children are at increased risk of severe influenza disease and, thus, are good candidates for receiving annual vaccination. Nevertheless, the influenza vaccine is infrequently given to children in our region. The primary objectives of this study are to monitor the serologic immunities against influenza A and B viruses, and provide pediatric data that support the need for influenza vaccination in the community. METHODS: Influenza A and B virus-specific IgG antibodies were measured in 294 children (median age 4...
August 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28792537/isolation-and-functional-characterization-of-hepatitis-b-virus-specific-t-cell-receptors-as-new-tools-for-experimental-and-clinical-use
#6
Karin Wisskirchen, Kai Metzger, Sophia Schreiber, Theresa Asen, Luise Weigand, Christina Dargel, Klaus Witter, Elisa Kieback, Martin F Sprinzl, Wolfgang Uckert, Matthias Schiemann, Dirk H Busch, Angela M Krackhardt, Ulrike Protzer
T-cell therapy of chronic hepatitis B is a novel approach to restore antiviral T-cell immunity and cure the infection. We aimed at identifying T-cell receptors (TCR) with high functional avidity that have the potential to be used for adoptive T-cell therapy. To this end, we cloned HLA-A*02-restricted, hepatitis B virus (HBV)-specific T cells from patients with acute or resolved HBV infection. We isolated 11 envelope- or core-specific TCRs and evaluated them in comprehensive functional analyses. T cells were genetically modified by retroviral transduction to express HBV-specific TCRs...
2017: PloS One
https://www.readbyqxmd.com/read/28789678/optimization-and-validation-of-sample-preparation-for-metagenomic-sequencing-of-viruses-in-clinical-samples
#7
Dagmara W Lewandowska, Osvaldo Zagordi, Fabienne-Desirée Geissberger, Verena Kufner, Stefan Schmutz, Jürg Böni, Karin J Metzner, Alexandra Trkola, Michael Huber
BACKGROUND: Sequence-specific PCR is the most common approach for virus identification in diagnostic laboratories. However, as specific PCR only detects pre-defined targets, novel virus strains or viruses not included in routine test panels will be missed. Recently, advances in high-throughput sequencing allow for virus-sequence-independent identification of entire virus populations in clinical samples, yet standardized protocols are needed to allow broad application in clinical diagnostics...
August 8, 2017: Microbiome
https://www.readbyqxmd.com/read/28783746/identification-of-unique-b-virus-macacine-herpesvirus-1-epitopes-of-zoonotic-and-macaque-isolates-using-monoclonal-antibodies
#8
David Katz, Wei Shi, Manjunath S Gowda, Mugdha Vasireddi, Irina Patrusheva, Hyuk-Kyu Seoh, Chadi N Filfili, Martin J Wildes, Jay Oh, Julia K Hilliard
Our overall aim is to develop epitope-based assays for accurate differential diagnosis of B virus zoonotic infections in humans. Antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with HSV types 1 and 2. To find B virus-specific epitopes we cloned ten monoclonal antibodies (mAbs) from the hybridomas we produced. Our unique collection of rare human sera from symptomatic and asymptomatic patients infected with B virus was key to the evaluation and identification of the mAbs as reagents in competition ELISAs (mAb-CE)...
2017: PloS One
https://www.readbyqxmd.com/read/28783452/off-the-shelf-virus-specific-t-cells-to-treat-bk-virus-human-herpesvirus-6-cytomegalovirus-epstein-barr-virus-and-adenovirus-infections-after-allogeneic-hematopoietic-stem-cell-transplantation
#9
Ifigeneia Tzannou, Anastasia Papadopoulou, Swati Naik, Kathryn Leung, Caridad A Martinez, Carlos A Ramos, George Carrum, Ghadir Sasa, Premal Lulla, Ayumi Watanabe, Manik Kuvalekar, Adrian P Gee, Meng-Fen Wu, Hao Liu, Bambi J Grilley, Robert A Krance, Stephen Gottschalk, Malcolm K Brenner, Cliona M Rooney, Helen E Heslop, Ann M Leen, Bilal Omer
Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6)...
August 7, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28768862/crystal-structure-of-the-n-terminal-half-of-the-traffic-controller-ul37-from-herpes-simplex-virus-type-1
#10
Andrea L Koenigsberg, Ekaterina E Heldwein
Inner tegument protein UL37 is conserved among all three subfamilies of herpesviruses. Studies of UL37 homologs from two alphaherpesviruses, Herpes Simplex virus Type 1 (HSV-1) and pseudorabies virus (PRV), have suggested that UL37 plays an essential albeit poorly defined role in intracellular capsid trafficking. At the same time, HSV and PRV homologs cannot be swapped, which suggests that in addition to a conserved function, UL37 homologs may also have divergent virus-specific functions. Accurate dissection of UL37 functions requires detailed maps in the form of atomic-resolution structures...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28765225/b-cell-requirement-for-robust-regulatory-t-cell-responses-to-friend-retrovirus-infection
#11
Tyler C Moore, Lorena M Gonzaga, Jennifer M Mather, Ronald J Messer, Kim J Hasenkrug
Regulatory T cells (Tregs) are immunosuppressive cells of the immune system that control autoimmune reactivity. Tregs also respond during immune reactions to infectious agents in order to limit immunopathological damage from potent effectors such as CD8(+) cytolytic T lymphocytes. We have used the Friend virus (FV) model of retroviral infection in mice to investigate how viral infections induce Tregs. During acute FV infection, there is significant activation and expansion of thymus-derived (natural) Tregs that suppress virus-specific CD8(+) T cell responses...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28747914/extrinsic-protein-tyrosine-phosphatase-non-receptor-22-signals-contribute-to-cd8-t-cell-exhaustion-and-promote-persistence-of-chronic-lymphocytic-choriomeningitis-virus-infection
#12
Tatiana Jofra, Giuseppe Galvani, Mirela Kuka, Roberta Di Fonte, Bechara G Mfarrej, Matteo Iannacone, Shahram Salek-Ardakani, Manuela Battaglia, Georgia Fousteri
A genetic variant of the protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with a wide range of autoimmune diseases; however, the reasons behind its prevalence in the general population remain not completely understood. Recent evidence highlights an important role of autoimmune susceptibility genetic variants in conferring resistance against certain pathogens. In this study, we examined the role of PTPN22 in persistent infection in mice lacking PTPN22 infected with lymphocytic choriomeningitis virus clone 13...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28741465/engineering-of-chimeric-protein-based-on-e-protein-domain-iii-of-tick-borne-encephalitis-virus-and-ompf-porin-of-yersinia-pseudotuberculosis
#13
Anna M Stenkova, Natalia S Chopenko, Ludmila A Davydova, Andrey N Mazeika, Evgeniya P Bystritskaya, Olga Y Portnyagina, Stanislav D Anastyuk, Dmitrii S Kulbatskii, Ekaterina N Lyukmanova, Dmitriy A Dolgikh, Eduard Y Kostetsky, Nina M Sanina
Tick-borne encephalitis poses a serious public health threat in the endemic regions. The disease treatment is restricted to symptomatic therapy, so great expectations are in the development of the prophylactic and therapeutic vaccines. The domain III of E protein of the tick-borne encephalitis virus is the main antigenic domain which includes virus-specific epitopes recognized by neutralizing antibodies. We have expressed, isolated and characterized the chimeric protein based on the fusion of domain III of E protein of the tick-borne encephalitis virus and bacterial porin OmpF from Yersinia pseudotuberculosis...
July 24, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28740496/evaluation-of-antigen-specific-igm-and-igg-production-during-an-in-vitro-peripheral-blood-mononuclear-cell-culture-assay
#14
Yoshiko Matsuda, Ryoichi Imamura, Shiro Takahara
The recent attention given to diseases associated with memory B-cell (mBC)-produced antibodies (Abs) suggests the need for a similar in vitro assay to evaluate the functions of mBCs. Here, we cultured peripheral blood mononuclear cells (PBMCs) with the intent to collect mBC-derived Abs in vitro and maintain their cell-cell contact-dependent interactions with helper T-cells. PBMCs were cultured with interleukin (IL)-21, CpG-oligodeoxynucleotides (ODN), phorbol myristate acetate (PMA), and phytohemagglutinin/leucoagglutinin (PHA-L) in 24-well flat-bottom plates (5 × 10(5) cells/well)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28738211/the-immunopathology-of-dengue-and-zika-virus-infections
#15
REVIEW
Abigail Culshaw, Juthathip Mongkolsapaya, Gavin R Screaton
A large proportion of the world's population live in areas with dengue virus (DENV) transmission resulting in tens of millions of symptomatic dengue cases each year. Serious complications following DENV infection occur more frequently in those suffering from a second or subsequent infection implicating virus-specific immunity as having a role in pathogenesis. In recent years outbreaks of the related Zika virus (ZIKV) have been associated with birth defects and neurological complications. As DENV and ZIKV share a viral vector sequential infections can occur...
July 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28737510/lymphocytes-transiently-expressing-virus-specific-t-cell-receptors-reduce-hepatitis-b-virus-infection
#16
Janine Kah, Sarene Koh, Tassilo Volz, Erica Ceccarello, Lena Allweiss, Marc Lütgehetmann, Antonio Bertoletti, Maura Dandri
Adoptive transfer of T cells engineered to express a hepatitis B virus-specific (HBV-specific) T cell receptor (TCR) may supplement HBV-specific immune responses in chronic HBV patients and facilitate HBV control. However, the risk of triggering unrestrained proliferation of permanently engineered T cells raises safety concerns that have hampered testing of this approach in patients. The aim of the present study was to generate T cells that transiently express HBV-specific TCRs using mRNA electroporation and to assess their antiviral and pathogenetic activity in vitro and in HBV-infected human liver chimeric mice...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28729706/sudan-ebolavirus-long-recovered-survivors-produce-gp-specific-abs-that-are-of-the-igg1-subclass-and-preferentially-bind-fc%C3%AE-ri
#17
Olga Radinsky, Avishay Edri, Michael Brusilovsky, Shlomit Fedida-Metula, Ariel Sobarzo, Orly Gershoni-Yahalom, Julius Lutwama, John Dye, Leslie Lobel, Angel Porgador
Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#18
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28722019/sustained-accumulation-of-antigen-presenting-cells-after-infection-promotes-local-t-cell-immunity
#19
Nicholas Collins, Katharina Hochheiser, Francis R Carbone, Thomas Gebhardt
Antigen-presenting cells (APC) such as dendritic cells (DC) and macrophages are critical for T cell-mediated immunity. While it is established that memory T cells accumulate and persist in peripheral tissues after the resolution of infection, whether this is also the case for APC remains unclear. Here, we report that CCR2-dependent cells infiltrate skin during acute infection with herpes simplex virus (HSV)-1 and subsequently give rise to localized populations of dendritic cells and macrophages. These APC are found at elevated numbers at sites of resolved infection or inflammation compared to unaffected regions of skin...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28721503/salinity-drives-the-virioplankton-abundance-but-not-production-in-tropical-coastal-lagoons
#20
Pedro C Junger, André M Amado, Rodolfo Paranhos, Anderson S Cabral, Saulo M S Jacques, Vinicius F Farjalla
Viruses are the most abundant components of microbial food webs and play important ecological and biogeochemical roles in aquatic ecosystems. Virioplankton is regulated by several environmental factors, such as salinity, turbidity, and humic substances. However, most of the studies aimed to investigate virioplankton regulation were conducted in temperate systems combining a limited range of environmental variables. In this study, virus abundance and production were determined and their relation to bacterial and limnological variables was assessed in 20 neighboring shallow tropical coastal lagoons that present wide environmental gradients of turbidity (2...
July 18, 2017: Microbial Ecology
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