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https://www.readbyqxmd.com/read/28926977/mouse-monoclonal-antibodies-generated-from-full-length-human-cereblon-detection-of-cereblon-protein-in-patients-with-multiple-myeloma
#1
Xiubao Chang, Qinqin Xu, Yuexian Hou, Cynthia Li, Ye Xu, A Keith Stewart
Immunomodulatory drugs (IMiDs) are profoundly active compounds in the treatment of patients with multiple myeloma (MM). However, despite the fact that treatment with IMiDs has dramatically improved survival for patients with MM, the majority of MM patients develop IMiDs resistance over time. We have found that expression of functional cereblon is required for IMiDs' action. In addition, it has been reported that cells expressing high levels of cereblon are resistant to proteasome inhibitor, implying that patients with high levels of cereblon should be resistant to proteasome inhibitor...
September 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28925965/studying-the-structural-significance-of-galectin-design-by-playing-a-modular-puzzle-homodimer-generation-from-human-tandem-repeat-type-heterodimeric-galectin-8-by-domain-shuffling
#2
Anna-Kristin Ludwig, Malwina Michalak, Nadya Shilova, Sabine André, Herbert Kaltner, Nicolai V Bovin, Jürgen Kopitz, Hans-Joachim Gabius
Tissue lectins are emerging (patho)physiological effectors with broad significance. The capacity of adhesion/growth-regulatory galectins to form functional complexes with distinct cellular glycoconjugates is based on molecular selection of matching partners. Engineering of variants by changing the topological display of carbohydrate recognition domains (CRDs) provides tools to understand the inherent specificity of the functional pairing. We here illustrate its practical implementation in the case of human tandem-repeat-type galectin-8 (Gal-8)...
September 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28925296/vaccine-approaches-conferring-cross-protection-against-influenza-viruses
#3
Sai V Vemula, Ekramy E Sayedahmed, Suryaprakash Sambhara, Suresh K Mittal
Annual vaccination is one of the most efficient and cost-effective strategies to prevent and control influenza epidemics. Most of the currently available influenza vaccines are strong inducers of antibody responses against viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), but are poor inducers of cell-mediated immune responses against conserved internal proteins. Moreover, due to the high variability of viral surface proteins because of antigenic drift or antigenic shift, many of the currently licensed vaccines confer little or no protection against drift or shift variants...
September 19, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28924016/a-synthetic-glycan-microarray-enables-epitope-mapping-of-plant-cell-wall-glycan-directed-antibodies
#4
Colin Ruprecht, Max P Bartetzko, Deborah Senf, Pietro Dallabernardina, Irene Boos, Mathias C F Andersen, Toshihisa Kotake, J Paul Knox, Michael G Hahn, Mads H Clausen, Fabian Pfrengle
In the last three decades, more than 200 monoclonal antibodies have been raised against most classes of plant cell wall polysaccharides by different laboratories world-wide. These antibodies are widely used to identify differences in plant cell wall components in mutants, organ and tissue types, and developmental stages. Despite their importance and broad use, the precise binding epitope for only a few of these antibodies has been determined. Here, we use a plant glycan microarray equipped with 88 synthetic oligosaccharides to comprehensively map the epitopes of plant cell wall glycan-directed antibodies...
September 18, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28923982/emerging-concepts-in-tcr-specificity-rationalizing-and-maybe-predicting-outcomes
#5
REVIEW
Nishant K Singh, Timothy P Riley, Sarah Catherine B Baker, Tyler Borrman, Zhiping Weng, Brian M Baker
T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28923896/experimental-and-theoretical-approaches-to-investigate-the-immunogenicity-of-taenia-solium-derived-ke7-antigen
#6
Raúl J Bobes, José Navarrete-Perea, Adrián Ochoa-Leyva, Víctor Hugo Anaya, Marisela Hernández, Jacquelynne Cervantes-Torres, Karel Estrada, Filiberto Sánchez-Lopez, Xavier Soberón, Gabriela Rosas, Cáris Maroni Nunes, Martín García-Varela, Rogerio Rafael Sotelo-Mundo, Alonso Alexis López-Zavala, Goar Gevorkian, Gonzalo Acero, Juan P Laclette, Gladis Fragoso, Edda Sciutto
Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides, with proven protective capacity against cysticercosis, are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated to membrane processes and may participate in several vital cell pathways...
September 18, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28923089/dna-epigenome-editing-using-crispr-cas-suntag-directed-dnmt3a
#7
Yung-Hsin Huang, Jianzhong Su, Yong Lei, Lorenzo Brunetti, Michael C Gundry, Xiaotian Zhang, Mira Jeong, Wei Li, Margaret A Goodell
BACKGROUND: DNA methylation has widespread effects on gene expression during development. However, our ability to assign specific function to regions of DNA methylation is limited by the poor correlation between global patterns of DNA methylation and gene expression. RESULTS: Here, we utilize nuclease-deactivated Cas9 protein fused to repetitive peptide epitopes (SunTag) recruiting multiple copies of antibody-fused de novo DNA methyltransferase 3A (DNMT3A) (dCas9-SunTag-DNMT3A) to amplify the local DNMT3A concentration to methylate genomic sites of interest...
September 18, 2017: Genome Biology
https://www.readbyqxmd.com/read/28923084/viral-based-vaccine-tg4010-induces-broadening-of-specific-immune-response-and-improves-outcome-in-advanced-nsclc
#8
Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama, Xavier Préville
BACKGROUND: Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine. METHOD: The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922600/ptml-model-for-proteome-mining-of-b-cell-epitopes-and-theoretic-experimental-study-of-bm86-protein-sequences-from-colima-mexico
#9
Saúl Gabriel Martínez, Esvieta Tenorio-Borroto, Alberto Barbabosa Pliego, Hector Diaz-Albiter, Juan C Vazquez-Chagoyan, Humbert Gonzalez-Diaz
In this work, we developed a general Perturbation Theory and Machine Learning (PTML) method for data mining of proteomes, in order to discover new B-cell epitopes useful for vaccine design. The method predicts the epitope activity εq(cqj) of one query peptide (q-peptide) in a set of experimental query conditions (cqj). The method uses as input the sequence of the q-peptide. The method also uses as input information about the sequence and epitope activity εr(crj) of a peptide of reference (r-peptide) assayed on similar experimental conditions (crj)...
September 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28922578/identification-of-a-tetanus-toxin-specific-epitope-in-single-amino-acid-resolution
#10
Andrea Palermo, Laura K Weber, Simone Rentschler, Awale Isse, Martyna Sedlmayr, Karin Herbster, Volker List, Jürgen Hubbuch, Felix F Löffler, Alexander Nesterov-Müller, Frank Breitling
Vaccinations are among the most potent tools to fight infectious diseases. However, cross-reactions are an ongoing problem and there is an urgent need to fully understand the mechanisms of the immune response. For the development of a methodological workflow, the linear epitopes in the immune response to the tetanus toxin is investigated in sera of 19 vaccinated Europeans applying epitope mapping with peptide arrays. The most prominent epitope, appearing in nine different sera (923 IHLVNNESSEVIVHK937 ), is investigated in a substitution analysis to identify the amino acids that are crucial for the binding of the corresponding antibody species - the antibody fingerprint...
September 18, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28922413/exploitation-of-stable-nanostructures-based-on-the-mouse-polyomavirus-for-development-of-a-recombinant-vaccine-against-porcine-circovirus-2
#11
Martin Fraiberk, Michaela Hájková, Magdaléna Krulová, Martina Kojzarová, Alena Drda Morávková, Ivan Pšikal, Jitka Forstová
The aim of this study was to develop a suitable vaccine antigen against porcine circovirus 2 (PCV2), the causative agent of post-weaning multi-systemic wasting syndrome, which causes significant economic losses in swine breeding. Chimeric antigens containing PCV2b Cap protein sequences based on the mouse polyomavirus (MPyV) nanostructures were developed. First, universal vectors for baculovirus-directed production of chimeric MPyV VLPs or pentamers of the major capsid protein, VP1, were designed for their exploitation as vaccines against other pathogens...
2017: PloS One
https://www.readbyqxmd.com/read/28922374/fractional-laser-exposure-induces-neutrophil-infiltration-n1-phenotype-into-the-tumor-and-stimulates-systemic-anti-tumor-immune-response
#12
Masayoshi Kawakubo, Shadmehr Demehri, Dieter Manstein
BACKGROUND: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP...
2017: PloS One
https://www.readbyqxmd.com/read/28922082/combinatorial-peptide-based-epitope-mapping-from-ebola-virus-dna-vaccines-and-infections-reveals-residue-level-determinants-of-antibody-binding
#13
Daniel R Ripoll, Daniel A J Mitchell, Lesley C Dupuy, Anders Wallqvist, Connie Schmaljohn, Sidhartha Chaudhury
Ebola virus (EBOV) infection is highly lethal and results in severe febrile bleeding disorders that affect humans and non-human primates. One of the therapeutic approaches for treating EBOV infection focus largely on cocktails of monoclonal antibodies (mAbs) that bind to specific regions of the EBOV glycoprotein (GP) and neutralize the virus. Recent structural studies using cryo-electron microscopy have identified key epitopes for several EBOV mAbs. While such information has yielded deep insights into antibody binding, limitations on resolution of these structures often preclude a residue-level analysis of EBOV epitopes...
September 18, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28921501/immunological-tolerance-to-lcmv-antigens-differently-affects-control-of-acute-and-chronic-virus-infection-in-mice
#14
Christina Woopen, Tobias Straub, Oliver Schweier, Ulrike Aichele, Katharina Düker, Thomas Boehm, Hanspeter Pircher
Cytotoxic T lymphocytes (CTLs) play a key role in the control of lymphocytic choriomeningitis virus (LCMV) infection. In C57BL/6 mice (H-2(b) ), the CTL response is mainly directed against epitopes from the LCMV glycoprotein (GP) and the nucleoprotein (NP) which represent the two major viral proteins. The role of GP- versus NP-derived epitopes for viral clearance was examined using transgenic (tg) mice ubiquitously expressing LCMV GP and NP, respectively. These mice lack GP- or NP-specific CTLs and show decreased levels of GP- or NP-specific antibodies as a result of tolerance induction...
August 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28921428/production-of-recombinant-factor-viii-in-human-cell-lines
#15
Daianne Maciely Carvalho Fantacini, Virgínia Picanço-Castro
Human cell lines can produce recombinant proteins much more similar to their natural counterpart, compared to other mammalian cell lines, reducing potential immunogenic reactions. Recombinant proteins produced in nonhuman cells can have in its structure glycan epitopes, such as Galα1,3-Gal (alpha-Gal) and N-glycolylneuraminic acid (Neu5Gc) residues, that are antigenic to humans and can potentially affect the efficacy of the recombinant product. Therefore, the production of recombinant factor VIII (rFVIII) in human cell lines is a new approach to avoid nonhuman glycosylation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28919988/identification-of-a-hla-a-0201-restricted-immunogenic-epitope-from-the-universal-tumor-antigen-depdc1
#16
Anna Tosi, Silvia Dalla Santa, Elisa Cappuzzello, Carolina Marotta, Dawid Walerich, Giannino Del Sal, Paola Zanovello, Roberta Sommaggio, Antonio Rosato
The identification of universal tumor-specific antigens shared between multiple patients and/or multiple tumors is of great importance to overcome the practical limitations of personalized cancer immunotherapy. Recent studies support the involvement of DEPDC1 in many aspects of cancer traits, such as cell proliferation, resistance to induction of apoptosis and cell invasion, suggesting that it may play key roles in the oncogenic process. In this study, we report that DEPDC1 expression is upregulated in most types of human tumors, and closely linked to a poorer prognosis; therefore, it might be regarded as a novel universal oncoantigen potentially suitable for targeting many different cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919551/identification-of-potential-antigens-from-non-classically-secreted-proteins-and-designing-novel-multitope-peptide-vaccine-candidate-against-brucella-melitensis-through-reverse-vaccinology-and-immunoinformatics-approach
#17
Udayakumar S Vishnu, Jagadesan Sankarasubramanian, Paramasamy Gunasekaran, Jeyaprakash Rajendhran
Brucella melitensis is an intracellular pathogen resides in the professional and non-professional phagocytes of the host, causing zoonotic disease brucellosis. The stealthy nature of the Brucella makes it's highly pathogenic, and it is hard to eliminate the bacteria completely from the infected host. Hitherto, no licensed vaccines are available for human brucellosis. In this study, we identified potential antigens for vaccine development from non-classically secreted proteins through reverse vaccinology approach...
September 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28919034/a-sensitive-and-specific-lateral-flow-assay-for-rapid-detection-of-antibodies-against-glycoprotein-b-of-aujeszky-s-disease-virus
#18
Veronika V Vrublevskaya, Vladimir N Afanasyev, Andrey A Grinevich, Yuri Y Skarga, Pavel P Gladyshev, Sagila A Ibragimova, Dmitry V Krylsky, Sergey V Dezhurov, Oleg S Morenkov
A direct double antibody lateral flow assay (DDA-gB-LFA) for the detection of antibodies against the glycoprotein B (gB) of Aujeszky's disease virus (ADV) in swine sera was developed. A native ADV gB was used for the preparation of a conjugate with colloidal gold particles and the immobilization on the strip membrane. The gB purified from ADV virions by immunoaffinity chromatography retained its native epitope structure after adsorption on the nitrocellulose membrane and the surface of colloidal gold particles...
September 14, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28917539/hemagglutinin-specific-cd4-t-cell-responses-following-2009-ph1n1-inactivated-split-vaccine-inoculation-in-humans
#19
Shuguang Tan, Shihong Zhang, Bin Wu, Yingze Zhao, Wei Zhang, Min Han, Ying Wu, Guoli Shi, Yingxia Liu, Jinghua Yan, Guizhen Wu, Hua Wang, George F Gao, Fengcai Zhu, William J Liu
Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccine's protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine...
September 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28917537/hbcag-produced-in-transgenic-tobacco-triggers-th1-and-th2-response-when-intramuscularly-delivered
#20
Marcin Pyrski, Anna Rugowska, Kamil Robert Wierzbiński, Anna Kasprzyk, Maria Bogusiewicz, Piotr Bociąg, Sławomir Samardakiewicz, Marcin Czyż, Maciej Kurpisz, Tomasz Pniewski
Hepatitis B core Antigen (HBcAg) assembled into Capsid-Like Particles (CLPs) is investigated as a therapeutic vaccine in treatment of chronic hepatitis B (CHB) and in diagnostic tests or as a carrier for various epitopes. While the expression of HBcAg has been thoroughly clarified in E. coli and yeast, it has also been investigated in other expression systems. Stably transformed tobacco expressed HBcAg at a level of 110-250µg/g fresh weight, therefore in view of its large leaf biomass it offers a production platform comparable with transient expression systems regarding the final yield of HBcAg...
September 13, 2017: Vaccine
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