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antibody design

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https://www.readbyqxmd.com/read/28102754/enhancement-of-antibody-functions-through-fc-multiplications
#1
Qun Wang, Yan Chen, Mark Pelletier, Romana Cvitkovic, Jessica Bonnell, Chien-Ying Chang, Adem C Koksal, Ellen O'Connor, Xizhe Gao, Xiang-Qing Yu, Herren Wu, C Kendall Stover, William F Dall'Acqua, Xiaodong Xiao
Antibodies carry out a plethora of functions through their crystallizable fragment (Fc) regions, which can be naturally tuned by the adoption of several isotypes and post-translational modifications. Protein engineering enables further Fc function modulations through modifications of the interactions between the Fc and its functional partners, including FcγR, FcRn, complement complex, and additions of auxiliary functional units. Due to the many functions embedded within the confinement of an Fc, a suitable balance must be maintained for a therapeutic antibody to be effective and safe...
January 19, 2017: MAbs
https://www.readbyqxmd.com/read/28099492/priming-cross-protective-bovine-viral-diarrhea-virus-specific-immunity-using-live-vectored-mosaic-antigens
#2
Shehnaz Lokhandwala, Xin Fang, Suryakant D Waghela, Jocelyn Bray, Leo M Njongmeta, Andy Herring, Karim W Abdelsalam, Christopher Chase, Waithaka Mwangi
Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28098746/marine-antibody-drug-conjugates-design-strategies-and-research-progress
#3
REVIEW
Yu-Jie Wang, Yu-Yan Li, Xiao-Yu Liu, Xiao-Ling Lu, Xin Cao, Bing-Hua Jiao
Antibody-drug conjugates (ADCs), constructed with monoclonal antibodies (mAbs), linkers, and natural cytotoxins, are innovative drugs developed for oncotherapy. Owing to the distinctive advantages of both chemotherapy drugs and antibody drugs, ADCs have obtained enormous success during the past several years. The development of highly specific antibodies, novel marine toxins' applications, and innovative linker technologies all accelerate the rapid R&D of ADCs. Meanwhile, some challenges remain to be solved for future ADCs...
January 13, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28096941/transport-of-biomolecules-to-binding-partners-displayed-on-the-surface-of-microbeads-arrayed-in-traps-in-a-microfluidic-cell
#4
Xiaoxiao Chen, Thomas F Leary, Charles Maldarelli
Arrays of probe molecules integrated into a microfluidic cell are utilized as analytical tools to screen the binding interactions of the displayed probes against a target molecule. These assay platforms are useful in enzyme or antibody discovery, clinical diagnostics, and biosensing, as their ultraminiaturized design allows for high sensitivity and reduced consumption of reagents and target. We study here a platform in which the probes are first grafted to microbeads which are then arrayed in the microfluidic cell by capture in a trapping course...
January 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28096698/burkitt-lymphoma-in-adolescents-and-young-adults-management-challenges
#5
REVIEW
Massimo Dozzo, Francesca Carobolante, Pietro Maria Donisi, Annamaria Scattolin, Elena Maino, Rosaria Sancetta, Piera Viero, Renato Bassan
About one-half of all Burkitt lymphoma (BL) patients are younger than 40 years, and one-third belong to the adolescent and young adult (AYA) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. BL is an aggressive B-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-MYC genes. It presents as sporadic, endemic, or epidemic disease. Endemicity is pathogenetically linked to an imbalance of the immune system which occurs in African children infected by malaria parasites and Epstein-Barr virus, while the epidemic form strictly follows the pattern of infection by HIV...
2017: Adolescent Health, Medicine and Therapeutics
https://www.readbyqxmd.com/read/28096331/one-step-design-of-a-stable-variant-of-the-malaria-invasion-protein-rh5-for-use-as-a-vaccine-immunogen
#6
Ivan Campeotto, Adi Goldenzweig, Jack Davey, Lea Barfod, Jennifer M Marshall, Sarah E Silk, Katherine E Wright, Simon J Draper, Matthew K Higgins, Sarel J Fleishman
Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096174/anti-folate-receptor-%C3%AE-ige-but-not-igg-recruits-macrophages-to-attack-tumors-via-tnf-%C3%AE-mcp-1-signaling
#7
Debra H Josephs, Heather J Bax, Tihomir Dodev, Mirella Georgouli, Mano Nakamura, Giulia Pellizzari, Louise Saul, Panagiotis Karagiannis, Anthony Cheung, Cecilia Herraiz, Kristina M Ilieva, Isabel Correa, Matthew Fittall, Silvia Crescioli, Patrycja Gazinska, Natalie Woodman, Silvia Mele, Giulia Chiaruttini, Amy E Gilbert, Alexander Koers, Marguerite Bracher, Christopher Selkirk, Heike Lentfer, Claire Barton, Elliott Lever, Gareth Muirhead, Sophia Tsoka, Silvana Canevari, Mariangela Figini, Ana Montes, Noel Downes, David Dombrowicz, Christopher Corrigan, Andrew J Beavil, Frank O Nestle, Paul S Jones, Hannah J Gould, Victoria Sanz-Moreno, Philip J Blower, James Spicer, Sophia N Karagiannis
IgE antibodies are key mediators of anti-parasitic immune responses, but their potential for cancer treatment via antibody-directed cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen-specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages, however, the underlying therapeutic mechanisms were undefined and in vivo proof-of-concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fcε receptor system for cancer studies...
January 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28095712/current-views-on-the-potential-for-development-of-a-hiv-vaccine
#8
Kristen W Cohen, Nicole Frahm
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28094996/characterization-of-protein-excipient-microheterogeneity-in-biopharmaceutical-solid-state-formulations-by-confocal-fluorescence-microscopy
#9
Stijn H S Koshari, Jean L Ross, Purnendu K Nayak, Isidro E Zarraga, Karthikan Rajagopal, Norman J Wagner, Abraham M Lenhoff
Protein-stabilizer microheterogeneity is believed to influence long-term protein stability in solid-state biopharmaceutical formulations and its characterization is therefore essential for the rational design of stable formulations. However, the spatial distribution of the protein and the stabilizer in a solid-state formulation is, in general, difficult to characterize because of the lack of a functional, simple, and reliable characterization technique. We demonstrate the use of confocal fluorescence microscopy with fluorescently labeled monoclonal antibodies (mAbs) and antibody fragments (Fabs) to directly visualize three-dimensional particle morphologies and protein distributions in dried biopharmaceutical formulations, without restrictions on processing conditions or the need for extensive data analysis...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28094577/protective-role-of-bentonite-against-aflatoxin-b1-and-ochratoxin-a-induced-immunotoxicity-in-broilers
#10
Sheraz Ahmed Bhatti, Muhammad Zargham Khan, Muhammad Kashif Saleemi, Muhammad Saqib, Ahrar Khan, Zahoor Ul-Hassan
The present study was designed to investigate any ameliorative effects of bentonite (BN) against immuno-pathological alterations induced by dietary aflatoxin B1 (AFB1) or ochratoxin A (OTA) in broiler chicks. In one experiment, AFB1 (0.1, 0.2 or 0.6 mg/kg feed) was fed alone and par alley with bentonite clay (3.7 or 7.5 g/kg feed) to the broilers. In the second experiment, the broilers were given feed contaminated with OTA (0.15, 0.3 or 1.0 mg/kg feed) alone and in combination with bentonite clay (3...
January 17, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28094093/achiralpentagonalpolyhedralframework-forcharacterizingviruscapsidstructures
#11
REVIEW
Aditya Raguram, V Sasisekharan, Ram Sasisekharan
Recent developments of rational strategies for the design of antiviral therapies, including monoclonal antibodies (mAbs), have naturally relied extensively on available viral structural information. As new strategies continue to be developed, it is equally important to continue to refine our understanding and interpretation of viral structural data. There are known limitations to the traditional (Caspar-Klug) theory for describing virus capsid structures that involves subdividing a capsid into triangular subunits...
January 13, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28093528/a-b-cell-epitope-peptide-derived-from-the-major-grass-pollen-allergen-phl-p-1-boosts-allergen-specific-secondary-antibody-responses-without-allergen-specific-t-cell-help
#12
Meena Narayanan, Raphaela Freidl, Margarete Focke-Tejkl, Ulrike Baranyi, Thomas Wekerle, Rudolf Valenta, Birgit Linhart
More than 40% of allergic patients suffer from grass pollen allergy. Phl p 1, the major timothy grass pollen allergen, belongs to the cross-reactive group 1 grass pollen allergens that are thought to initiate allergic sensitization to grass pollen. Repeated allergen encounter boosts allergen-specific IgE production and enhances clinical sensitivity in patients. To investigate immunological mechanisms underlying the boosting of allergen-specific secondary IgE Ab responses and the allergen epitopes involved, a murine model for Phl p 1 was established...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28092616/generation-and-characterization-of-a-monoclonal-antibody-against-duck-tembusu-virus-envelope-protein
#13
K Han, D Zhao, Y Liu, Q Liu, X Huang, J Yang, K Bi, T Xu, Y Li
Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. Envelope (E) protein of DTMUV is an important structural protein, which is able to induce protective immune response in target animals and can be used as specific serological diagnosis tool. In this study, a novel monoclonal antibody, designated mAb 3E9, was generated against DTMUV E protein. It is positive in indirect ELISA against both His-E protein and the purified whole viral antigen...
December 1, 2016: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28092380/chromatin-immunoprecipitation-in-microfluidic-droplets-towards-fast-and-cheap-analyses
#14
Bruno Teste, Jerome Champ, Arturo Londono-Vallejo, Stéphanie Descroix, Laurent Malaquin, Jean-Louis Viovy, Irena Draskovic, Guillaume Mottet
Genetic organization is governed by the interaction of DNA with histone proteins, and differential modifications of these proteins is a fundamental mechanism of gene regulation. Histone modifications are primarily studied through chromatin immunoprecipitation (ChIP) assays, however conventional ChIP procedures are time consuming, laborious and require a large number of cells. Here we report for the first time the development of ChIP in droplets based on a microfluidic platform combining nanoliter droplets, magnetic beads (MB) and magnetic tweezers (MT)...
January 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28090753/inferring-infection-hazard-in-wildlife-populations-by-linking-data-across-individual-and-population-scales
#15
Kim M Pepin, Shannon L Kay, Ben D Golas, Susan S Shriner, Amy T Gilbert, Ryan S Miller, Andrea L Graham, Steven Riley, Paul C Cross, Michael D Samuel, Mevin B Hooten, Jennifer A Hoeting, James O Lloyd-Smith, Colleen T Webb, Michael G Buhnerkempe
Our ability to infer unobservable disease-dynamic processes such as force of infection (infection hazard for susceptible hosts) has transformed our understanding of disease transmission mechanisms and capacity to predict disease dynamics. Conventional methods for inferring FOI estimate a time-averaged value and are based on population-level processes. Because many pathogens exhibit epidemic cycling and FOI is the result of processes acting across the scales of individuals and populations, a flexible framework that extends to epidemic dynamics and links within-host processes to FOI is needed...
January 16, 2017: Ecology Letters
https://www.readbyqxmd.com/read/28090318/dengue-virus-antibodies-enhance-zika-virus-infection
#16
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Scott F Michael, Sharon Isern
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090276/overexpression-of-recombinant-human-teriparatide-rhpth-1-34-in-escherichia-coli-an-innovative-gene-fusion-approach
#17
Nahid Bakhtiari, Zahra Amini Bayat, Sepideh Sagharidouz, Mohsen Vaez
BACKGROUND: Parathyroid hormone is an 84-amino acid peptide secreted by the parathyroid glands. Its physiological role is maintenance of normal serum calcium level and bone remodeling. Biological activity of this hormone is related to N-terminal 1-34 amino acids. The recombinant form of hormone (1-34) has been approved for treatment of osteoporosis from 2002. In this study, a novel fusion partner has been developed for preparation of high yield recombinant 1-34 amino acids of hPTH. METHODS: Novel nucleotide cassette designed encoding a chimeric fusion protein comprising of a fusion partner consisting of a His-tag in N-terminal, 53 amino acids belong to Escherichia coli (E...
January 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28089881/two-step-chromatographic-purification-of-glutathione-s-transferase-tagged-human-papillomavirus-type-16-e6-protein-and-its-application-for-serology
#18
Mei Ling Xu, Seung Cheol Kim, Hyoung Jin Kim, Woong Ju, Yun Hwan Kim, Hong-Jin Kim
Human papillomavirus (HPV) E6 protein is an oncoprotein with a pivotal role in cervical carcinogenesis. Expression and purification of HPV E6 from Escherichia coli (E. coli) has been difficult because of its strong hydrophobicity even when expressed as a fusion protein with glutathione S-transferase (GST). There has been no protocol suggested for purifying GST-tagged HPV E6 protein with high purity so far. Herein, we provide efficient protocol for purifying GST-HPV16 E6 protein for the first time. In the current study, the GST-tagged protein was expressed in E...
January 9, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28088904/fc-fusion-proteins-in-therapy-an-updated-view
#19
Reza Jafari, Naime Majidi Zolbanin, Houshang Rafatpanah, Jafar Majidi, Tohid Kazemi
Fc-fusion proteins are composed of Fc region of IgG antibody (Hinge-CH2-CH3) and a desired linked protein. Fc region of Fc-fusion proteins can bind to neonatal Fc receptor (FcRn) thereby rescuing it from degradation. The first therapeutic Fc-fusion protein was introduced for treatment of AIDS. The molecular designing is the first stage in production of Fc-fusion proteins. The amino acid residues in the Fc region and linked protein are very important in the bioactivity and affinity of the fusion proteins. Although, therapeutic monoclonal antibodies are the top selling biologics but the application of therapeutic Fc-fusion proteins in clinic is in progress and among of these medications Etanercept is the most effective in therapy...
January 13, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28088476/a-chimeric-protein-of-abrin-and-abrus-precatorius-agglutinin-that-neutralizes-abrin-mediated-lethality-in-mice
#20
Vinita Tiwari, Shradha Bagaria, Anjali A Karande
Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
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