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antibody design

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https://www.readbyqxmd.com/read/29458022/generation-of-anti-oligosaccharide-antibodies-that-recognize-mammalian-glycoproteins-by-immunization-with-a-novel-artificial-glycosphingolipid
#1
Tetsuya Okuda, Asami Fukui
Here we report a new method for the efficient generation of antibodies that recognize the fine structures of oligosaccharides on glycoproteins. We found a newly designed artificial glycosphingolipid carrying a very long chain fatty acid to be a strong immunogen in mice, with the serum of immunized mice containing antibodies recognizing the oligosaccharide structure of the immunogen. First, we found that conjugation of a simple ceramide analogue to target oligosaccharides could enhance the immunogenicity of these oligosaccharides in these immunized mice...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29455062/enhanced-contraception-of-canine-zona-pellucida-3-dna-vaccine-via-targeting-dec-205-in-mice
#2
Ying Wang, Beibei Zhang, Jinyao Li, Adila Aipire, Yijie Li, Fuchun Zhang
Zona pellucida 3 (ZP3) is a potential antigen for the development of contraceptive vaccines to control animal population. In this study, we designed a canine ZP3 (CZP3) DNA vaccine through targeting DEC-205 (named as pcD-scFv-CZP3c) and investigated its contraceptive effect in mice. Female BALB/c mice were intramuscularly immunized 3 times at 2 weeks intervals. After immunization, humoral and cellular immune responses were detected by ELISA and flow cytometry. The results showed that pcD-CZP3 and pcD-scFv-CZP3c induced CZP3-specific antibody (Ab) responses both in serum and vaginal secretions compared to pcDNA3...
February 9, 2018: Theriogenology
https://www.readbyqxmd.com/read/29454703/synthesis-and-evaluation-of-novel-dolastatin-10-derivatives-for-versatile-conjugations
#3
Shinya Yokosaka, Akiko Izawa, Chizuka Sakai, Eri Sakurada, Yasuhiro Morita, Yukihiro Nishio
Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50 < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs...
February 11, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29454575/targeting-complement-mediated-immunoregulation-for-cancer-immunotherapy
#4
REVIEW
Martin Kolev, Maciej M Markiewski
Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response...
February 14, 2018: Seminars in Immunology
https://www.readbyqxmd.com/read/29453628/safety-tolerability-and-preliminary-activity-of-imgn529-a-cd37-targeted-antibody-drug-conjugate-in-patients-with-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-a-dose-escalation-phase-i-study
#5
Anastasios Stathis, Ian W Flinn, Sumit Madan, Kami Maddocks, Arnold Freedman, Steven Weitman, Emanuele Zucca, Mihaela C Munteanu, M Lia Palomba
Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29453596/effectiveness-of-the-sesquiterpene-%C3%AE-bisabolol-in-dogs-with-naturally-acquired-canine-leishmaniosis-an-exploratory-clinical-trial
#6
V Corpas-López, G Merino-Espinosa, C Acedo-Sánchez, V Díaz-Sáez, M C Navarro-Moll, F Morillas-Márquez, J Martín-Sánchez
The use of natural products is a promising approach for treating visceral leishmaniosis. (-)-α-Bisabolol is a sesquiterpene that have been proved active in vivo on Leishmania infantum-infected mice without showing toxicity. A single-centre, parallel-group, randomized, exploratory study was designed to assess its efficacy in a canine leishmaniosis model involving naturally infected dogs. In this clinical trial, 12 dogs were allocated into two groups and were treated with either meglumine antimoniate (100 mg/kg) through subcutaneous route or (-)-α-bisabolol (30 mg/kg) through oral route for two treatment series of 30 days, separated by a 30-day interval...
February 16, 2018: Veterinary Research Communications
https://www.readbyqxmd.com/read/29453420/a-multiplex-serologic-platform-for-diagnosis-of-tick-borne-diseases
#7
Rafal Tokarz, Nischay Mishra, Teresa Tagliafierro, Stephen Sameroff, Adrian Caciula, Lokendrasingh Chauhan, Jigar Patel, Eric Sullivan, Azad Gucwa, Brian Fallon, Marc Golightly, Claudia Molins, Martin Schriefer, Adriana Marques, Thomas Briese, W Ian Lipkin
Tick-borne diseases are the most common vector-borne diseases in the United States, with serology being the primary method of diagnosis. We developed the first multiplex, array-based assay for serodiagnosis of tick-borne diseases called the TBD-Serochip. The TBD-Serochip was designed to discriminate antibody responses to 8 major tick-borne pathogens present in the United States, including Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, Ehrlichia chaffeensis, Rickettsia rickettsii, Heartland virus and Powassan virus...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453292/clonal-selection-drives-protective-memory-b-cell-responses-in-controlled-human-malaria-infection
#8
Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E Busse, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Peter G Kremsner, Benjamin Mordmüller, Thomas Höfer, Hedda Wardemann
Affinity maturation, the clonal selection and expansion of antigen-activated B cells expressing somatically mutated antibody variants that develop during T cell-dependent germinal center reactions, is considered pivotal for efficient development of protective B cell memory responses to infection and vaccination. Repeated antigen exposure promotes affinity maturation but each time also recruits antigen-reactive naïve B cells into the response. Here, we determined the relative impact of affinity maturation versus antigen-mediated clonal selection of naïve B cells to mount potent B cell memory responses in humans after repeated exposure to a complex pathogen, the malaria parasite Plasmodium falciparum (Pf)...
February 16, 2018: Science Immunology
https://www.readbyqxmd.com/read/29451984/two-component-ferritin-nanoparticles-for-multimerization-of-diverse-trimeric-antigens
#9
Ivelin S Georgiev, Michael Gordon Joyce, Rita E Chen, Kwanyee Leung, Krisha McKee, Aliaksandr Druz, Joseph G Van Galen, Masaru Kanekiyo, Yaroslav Tsybovsky, Eun Sung Yang, Yongping Yang, Priyamvada Acharya, Marie Pancera, Paul V Thomas, Timothy Wanninger, Hadi Yassine, Ulrich Baxa, Nicole Doria-Rose, Cheng Cheng, Barney S Graham, John R Mascola, Peter D Kwong
Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (twenty-four monomers or eight trimers) of a single antigen. Here we design two-component ferritin variants that allow the attachment of two diverse antigens on a single particle in a defined ratio and geometric pattern...
February 16, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29451898/integrating-linear-optimization-with-structural-modeling-to-increase-hiv-neutralization-breadth
#10
Alexander M Sevy, Swetasudha Panda, James E Crowe, Jens Meiler, Yevgeniy Vorobeychik
Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29450991/mass-spectrometry-based-fast-photochemical-oxidation-of-proteins-fpop-for-higher-order-structure-characterization
#11
Ke Sherry Li, Liuqing Shi, Michael L Gross
Assessment of protein structure and interaction is crucial for understanding protein structure/function relationships. Compared to high-resolution structural tools, including X-ray crystallography, nuclear magnetic resonance (NMR), and cryo-EM, and traditional low-resolution methods, such as circular dichroism, UV-vis, and florescence spectroscopy, mass spectrometry (MS)-based protein footprinting affords medium-to-high resolution (i.e., regional and residue-specific insights) by taking advantage of proteomics methods focused on the primary structure...
February 16, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29450412/clinically-approved-liposomal-nanomedicines-lessons-learned-from-the-biomolecular-corona
#12
Giulio Caracciolo
Nowadays, liposomes are the most successful drug delivery systems with a dozen drug products available in the clinic. Grafting poly-(ethylene glycol) (PEG) onto the liposome surface prevents protein binding thus prolonging blood circulation, while synthetic modification of the terminal PEG molecule with ligands (e.g. monoclonal antibodies and peptides) should promote selective accumulation in the tumor region with respect to healthy tissues. However, despite big efforts, advances have not outgrown the development stage and just a few targeted liposomal drugs are commercially available...
February 16, 2018: Nanoscale
https://www.readbyqxmd.com/read/29449582/use-of-elispot-assay-to-study-hbs-specific-b-cell-responses-in-vaccinated-and-hbv-infected-humans
#13
Chen Tian, Yuxin Chen, Yong Liu, Shixia Wang, Yang Li, Guiyang Wang, Juan Xia, Xiang-An Zhao, Rui Huang, Shan Lu, Chao Wu
Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages, with or without a particular type anti-viral treatment, or whether receiving a dose of HBV vaccine...
February 16, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29449194/prostaglandin-d2-receptor-dp1-antibodies-predict-vaccine-induced-and-spontaneous-narcolepsy-type-1-large-scale-study-of-antibody-profiling
#14
Helle Sadam, Arno Pihlak, Anri Kivil, Susan Pihelgas, Mariliis Jaago, Priit Adler, Jaak Vilo, Olli Vapalahti, Toomas Neuman, Dan Lindholm, Markku Partinen, Antti Vaheri, Kaia Palm
BACKGROUND: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or antigens for the immune response have, however, remained elusive. METHODS: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA)...
February 2, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29448503/construction-and-characterization-of-cell-penetrating-peptide-fused-fibroblast-growth-factor-and-vascular-endothelial-growth-factor-for-an-enhanced-percutaneous-delivery-system
#15
Sang Won Choi, Rudra Pangeni, Dai Hyun Jung, Su Jung Kim, Jin Woo Park
The exogenous administration of growth factors has been examined for treating wounds and such factors serve as cosmetic agents for skin regeneration. However, the topical application of growth factors is hampered by their limited percutaneous absorption. In this study, we genetically modified basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) using a cell-penetrating peptide to facilitate their permeation into skin and to avoid multiple steps in the chemical or physical modification of biomaterials...
February 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29448116/immunoliposomes-in-clinical-oncology-state-of-the-art-and-future-perspectives
#16
REVIEW
María Merino, Sara Zalba, María J Garrido
Liposomal formulations entrapping a vast number of molecules have improved cancer therapies overcoming certain pharmacokinetic (PK) and pharmacodynamic limitations, many of which are associated with tumor characteristics. In this context, immunoliposomes represent a new strategy that has been widely investigated in preclinical cancer models with promising results, although few have reached the stage of clinical trials. This contrasts with the emerging clinical application of monoclonal antibodies (mAbs). This formulation allows the conjugation of different mAbs or antibody derivatives, such as monovalent variable fragments Fab', to the polymers covering the surface of liposomes...
February 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29446208/study-rationale-design-and-pre-transplant-alloantibody-status-a-first-report-of-clinical-trials-in-organ-transplantation-in-children-04-ctotc-04-in-pediatric-heart-transplantation
#17
Warren A Zuckerman, Adriana Zeevi, Kristen L Mason, Brian Feingold, Carol Bentlejewski, Linda J Addonizio, Elizabeth D Blume, Charles E Canter, Anne I Dipchand, Daphne T Hsu, Robert E Shaddy, William T Mahle, Anthony J Demetris, David M Briscoe, Thalachallour Mohanakumar, Joseph M Ahearn, David N Iklé, Brian D Armstrong, Yvonne Morrison, Helena Diop, Jonah Odim, Steven A Webber
Anti-HLA donor-specific antibodies are associated with worse outcomes following organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase post-transplant morbidity and mortality. We address this clinical challenge in a prospective, multi-center, observational cohort study of children listed for heart transplantation (CTOTC-04). Outcomes were compared among sensitized recipients who underwent transplant with positive crossmatch, non-sensitized recipients, and sensitized recipients without positive crossmatch...
February 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29444980/circulating-t-fh-cells-serological-memory-and-tissue-compartmentalization-shape-human-influenza-specific-b-cell-immunity
#18
Marios Koutsakos, Adam K Wheatley, Liyen Loh, E Bridie Clemens, Sneha Sant, Simone Nüssing, Annette Fox, Amy W Chung, Karen L Laurie, Aeron C Hurt, Steve Rockman, Martha Lappas, Thomas Loudovaris, Stuart I Mannering, Glen P Westall, Michael Elliot, Stuart G Tangye, Linda M Wakim, Stephen J Kent, Thi H O Nguyen, Katherine Kedzierska
Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T FH ) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5 - CXCR3 + antibody-secreting B cell population, CD21 hi CD27 + memory B cells, and CD21 lo CD27 + B cells...
February 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29444872/fviii-proteins-with-a-modified-immunodominant-t-cell-epitope-exhibit-reduced-immunogenicity-and-normal-fviii-activity
#19
Ruth A Ettinger, Joseph A Liberman, Devi Gunasekera, Komal Puranik, Eddie A James, Arthur R Thompson, Kathleen P Pratt
Factor VIII (FVIII)-neutralizing antibodies (inhibitors) are a serious complication in hemophilia A (HA). The peptide FVIII 2194-2213 contains an immunodominant HLA-DRA*01-DRB1*01:01 (DRB1*01:01)-restricted epitope recognized by CD4 + T-effector cells from HA subjects. The aim of this study was to identify amino acid substitutions to deimmunize this epitope while retaining procoagulant function and expression levels comparable to those of wild-type (WT) FVIII proteins. The shortest DRB1*01:01-binding peptide was FVIII 2194-2205 , and residues important for affinity were identified as F2196, M2199, A2201, and S2204...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29443890/embedded-disposable-functionalized-electrochemical-biosensor-with-a-3d-printed-flow-cell-for-detection-of-hepatic-oval-cells-hocs
#20
Samar Damiati, Martin Peacock, Stefan Leonhardt, Laila Damiati, Mohammed A Baghdadi, Holger Becker, Rimantas Kodzius, Bernhard Schuster
Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells...
February 14, 2018: Genes
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