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https://www.readbyqxmd.com/read/28736824/evaluation-of-lumazine-synthase-from-bacillus-anthracis-as-a-presentation-platform-for-polyvalent-antigen-display
#1
Yangjie Wei, Newton Wahome, Greta VanSlyke, Neal Whitaker, Prashant Kumar, Michael L Barta, Wendy L Picking, David B Volkin, Nicholas J Mantis, C Russell Middaugh
Polyvalent antigen display is an effective strategy to enhance the immunogenicity of subunit vaccines by clustering them in an array-like manner on a scaffold system. This strategy results in a higher local density of antigens, increased high avidity interactions with B cells and other antigen presenting cells, and therefore a more effective presentation of vaccine antigens. In the present study, we used lumazine synthase (LS), an icosahedral symmetry capsid derived from Bacillus anthracis, as a scaffold to present 60 copies of a linear B cell epitope (PB10) from the ricin toxin fused to the C terminus of LS via four different linkers...
July 24, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#2
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#3
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723519/individual-patient-data-analysis-of-randomized-clinical-trials-impact-of-black-race-on-castration-resistant-prostate-cancer-outcomes
#4
Daniel E Spratt, Yu-Wei Chen, Brandon A Mahal, Joseph R Osborne, Shuang G Zhao, Todd M Morgan, Ganesh Palapattu, Felix Y Feng, Paul L Nguyen
BACKGROUND: Population data suggest that black men have a higher risk of dying from prostate cancer (PCa) than other racial ethnicities. OBJECTIVE: To examine the impact of black race on progression-free survival (PFS) and overall survival (OS) among men with metastatic castration-resistant PCa (mCRPC) enrolled in randomized controlled trials (RCTs). DESIGN, SETTING, AND PARTICIPANTS: A pooled analysis was performed on individual patient data from five modern PCa RCTs available from Project Data Sphere...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28718065/structure-function-relationships-of-protein-lipopeptide-complexes-and-influence-on-immunogenicity
#5
Acep R Wijayadikusumah, Lucy C Sullivan, David C Jackson, Brendon Y Chua
The lipopeptide, R4Pam2Cys, associates electrostatically with soluble protein antigens and significantly enhances their ability to induce protective humoral and cell-mediated responses. We demonstrate that antibody titers elicited by the antigen ovalbumin (OVA) associated with R4Pam2Cys are higher than those elicited by OVA in the presence of alum and comparable to those elicited by OVA formulated with complete Freund's adjuvant (CFA). The hierarchy of anti-OVA antibody avidities was CFA > R4Pam2Cys = alum...
July 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#6
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#7
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28680446/donor-selection-for-allogenic-hemopoietic-stem-cell-transplantation-clinical-and-ethical-considerations
#8
REVIEW
Irene Riezzo, Natascha Pascale, Raffaele La Russa, Arcangelo Liso, Monica Salerno, Emanuela Turillazzi
Allogenic hematopoietic progenitor cell transplantation (allo-HSCT) is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA-) identical sibling donor the opportunity to find a donor and cord blood units worldwide...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28675899/serum-anticytokine-autoantibody-levels-are-not-increased-in-hidradenitis-suppurativa-a-case-control-pilot-study
#9
Peter Theut Riis, Jakob Hjorth von Stemann, Rune Kjærsgaard Andersen, Morten Bagge Hansen, Gregor B E Jemec
BACKGROUND: Hidradenitis suppurativa is a skin disease of recurrent episodes of inflammatory nodules, abscesses, and scarring of the intertriginous regions, e.g. the axillae and groin. A dysregulated immune response to one or more unknown antigens in hidradenitis suppurativa has been suggested. One hypothetical element of this dysregulation may be the functionality of the cytokines. This study examines the serum level of anticytokine autoantibodies for interleukin (IL)-1α, IL-6, IL-10, IL-17A, IL-17E, IL-17F, and interferon-α...
July 4, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28671856/overall-survival-in-patients-with-advanced-melanoma-who-received-nivolumab-versus-investigator-s-choice-chemotherapy-in-checkmate-037-a-randomized-controlled-open-label-phase-iii-trial
#10
James Larkin, David Minor, Sandra D'Angelo, Bart Neyns, Michael Smylie, Wilson H Miller, Ralf Gutzmer, Gerald Linette, Bartosz Chmielowski, Christopher D Lao, Paul Lorigan, Kenneth Grossmann, Jessica C Hassel, Mario Sznol, Adil Daud, Jeffrey Sosman, Nikhil Khushalani, Dirk Schadendorf, Christoph Hoeller, Dana Walker, George Kong, Christine Horak, Jeffrey Weber
Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator's choice chemotherapy (ICC; dacarbazine 1,000 mg/m(2) every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m(2) every 3 weeks)...
July 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28658771/a1-and-a2-sub-types-of-blood-group-a-a-reflection-of-their-prevalence-in-north-karnataka-region
#11
Sujata S Giriyan, Akanksha Agrawal, Richa Bajpai, Niraj Kumar Nirala
INTRODUCTION: Landsteiner ABO system of blood groups is most important for transfusion medicine and has subtypes of A Antigen, A1 and A2, upon which further groups of A and AB have been classified. Of individuals with A antigen, approximately 20% belong to A2 while rest 80% belong to A1. Anti-A1 Lectin, a cold agglutinin which destroys A1 cells is clinically significant when they react at 37°C, causing transfusion reactions. AIM: To assess the prevalence of A1 and A2 subgroups in the population...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28651680/full-genome-sequence-analysis-of-an-uncommon-norovirus-genotype-gii-21-from-south-korea
#12
J W Lee, S G Lee, H G Cho, Y J Park, J W Yun, C J Park, S Y Paik
Noroviruses (NoVs) are major causal agents of acute gastroenteritis in humans. NoV GII.4 is the predominant genotype globally. However, uncommon and minor types of NoVs are consistently detected and some have been shown to dominate over GII.4. Therefore, the prevalence of dominant and uncommon NoVs makes the identification of these viruses important for the prediction and prevention of pandemics. In this study, the full-genome sequence of a NoV (strain JW) detected in Korea was extensively characterized. The full-length genome was 7510 nucleotides long, and phylogenetic analysis based on the whole-genome sequences, including open reading frame (ORF)1, ORF2, and ORF3, indicated that it belonged to the GII...
June 27, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28651066/thalassemia-major-transfusion-and-chelation-or-transplantation
#13
REVIEW
Said Yousuf Mohamed
Thalassemia is the most common monogenic hematologic disease that affects millions in the world and kills thousands of patients every year. Without transfusion or transplantation, patients with thalassemia major are expected to die within months of diagnosis. However, long-term transfusion and chelation therapy is highly challenging for many developing countries where the disease is prevalent, representing a major and unsustainable health burden. Stem cell transplantation is the only cure for thalassemia. It has witnessed major developments that have made it less toxic, more successful, and feasible for a larger number of patients with diverse comorbidities and from a wider range of donors...
June 20, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28650991/distinguishing-functional-polymorphism-from-random-variation-in-the-sequences-of-10-000-hla-a-b-and-c-alleles
#14
James Robinson, Lisbeth A Guethlein, Nezih Cereb, Soo Young Yang, Paul J Norman, Steven G E Marsh, Peter Parham
HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles. This analysis required development of suites of methods, having general applicability, for comparing and analyzing large numbers of homologous sequences. At least three amino-acid substitutions are present at every position in the polymorphic α1 and α2 domains of HLA-A, -B and -C...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28650381/potential-for-immune-driven-viral-polymorphisms-to-compromise-antiretroviral-based-pre-exposure-prophylaxis-for-prevention-of-hiv-1-infection
#15
Hiroyuki Gatanaga, Zabrina L Brumme, Emily Adland, Gustavo Reyes-Terán, Santiago Avila-Rios, Carlos R Mejía-Villatoro, Tsunefusa Hayashida, Takayuki Chikata, Giang Van Tran, Kinh Van Nguyen, Rita I Meza, Elsa Y Palou, Humberto Valenzuela-Ponce, Juan M Pascale, Guillermo Porras-Cortés, Marvin Manzanero, Guinevere Q Lee, Jeffrey N Martin, Mary N Carrington, Mina John, Simon Mallal, Art F Y Poon, Philip Goulder, Masafumi Takiguchi, Shinichi Oka
OBJECTIVE: Long-acting rilpivirine is a candidate for pre-exposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (RT-E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing Human Leukocyte Antigen (HLA)-B*18 where RT-E138X arises as an immune escape mutation. We investigate the global prevalence, B*18-linkage and replicative cost of RT-E138X and its regional implications for rilpivirine PrEP...
June 23, 2017: AIDS
https://www.readbyqxmd.com/read/28638837/validation-of-a-novel-immunoline-assay-for-patient-stratification-according-to-virulence-of-the-infecting-helicobacter-pylori-strain-and-eradication-status
#16
Luca Formichella, Laura Romberg, Hannelore Meyer, Christian Bolz, Michael Vieth, Michael Geppert, Gereon Göttner, Christina Nölting, Wolfgang Schepp, Arne Schneider, Kurt Ulm, Petra Wolf, Ingrid Lisanne Holster, Ernst J Kuipers, Bernd Birkner, Erwin Soutschek, Markus Gerhard
Helicobacter pylori infection shows a worldwide prevalence of around 50%. However, only a minority of infected individuals develop clinical symptoms or diseases. The presence of H. pylori virulence factors, such as CagA and VacA, has been associated with disease development, but assessment of virulence factor presence requires gastric biopsies. Here, we evaluate the H. pylori recomLine test for risk stratification of infected patients by comparing the test score and immune recognition of type I or type II strains defined by the virulence factors CagA, VacA, GroEL, UreA, HcpC, and gGT with patient's disease status according to histology...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#17
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28633071/structural-characterization-of-the-immunostimulatory-exopolysaccharide-produced-by-leuconostoc-mesenteroides-strain-ntm048
#18
Chiaki Matsuzaki, Chikahiro Takagaki, Yusuke Tomabechi, Lennart S Forsberg, Christian Heiss, Parastoo Azadi, Kenji Matsumoto, Toshihiko Katoh, Koji Hosomi, Jun Kunisawa, Kenji Yamamoto, Keiko Hisa
The exopolysaccharide (EPS) produced by probiotic Leuconostoc mesenteroides subsp. mesenteroides strain NTM048 has been reported to be an immunostimulant that enhances mucosal IgA production. In this study, we found that intranasal administration of mice with the EPS and an antigen (ovalbumin) resulted in secretion of antigen-specific IgA and IgG in the airway mucosa and the serum, suggesting that the EPS has the adjuvant activity for use with mucosal vaccination. Methylation analysis coupled to GC-MS, and 1D and 2D NMR spectroscopy revealed that 94% of the EPS consists of an α-(1 → 6) glucan containing 4% of 1→3-linked α-glucose branches...
June 15, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28626952/multivariate-binary-classification-of-imbalanced-datasets-a-case-study-based-on-high-dimensional-multiplex-autoimmune-assay-data
#19
Laura Schlieker, Anna Telaar, Angelika Lueking, Peter Schulz-Knappe, Carmen Theek, Katja Ickstadt
The classification of a population by a specific trait is a major task in medicine, for example when in a diagnostic setting groups of patients with specific diseases are identified, but also when in predictive medicine a group of patients is classified into specific disease severity classes that might profit from different treatments. When the sizes of those subgroups become small, for example in rare diseases, imbalances between the classes are more the rule than the exception and make statistical classification problematic when the error rate of the minority class is high...
June 19, 2017: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/28620645/alloimmunity-but-not-viral-immunity-promotes-allograft-loss-in-a-mouse-model-of-polyomavirus-associated-allograft-injury
#20
Steven C Kim, Jun Wang, Ying Dong, David V Mathews, Joshua A Albrecht, Cynthia P Breeden, Alton B Farris, Aron E Lukacher, Mandy L Ford, Kenneth A Newell, Andrew B Adams
BACKGROUND: The interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question. METHODS: We used a mouse model of polyomavirus (PyV) infection and kidney transplantation to investigate the roles of direct viral pathology, the antiviral immune response, and alloimmunity in the pathogenesis of PyV-associated allograft injury...
June 2017: Transplantation Direct
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