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Epitope mapping

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https://www.readbyqxmd.com/read/28729665/identification-of-proteins-that-specifically-recognize-and-bind-protofibrillar-aggregates-of-amyloid-%C3%AE
#1
Elisabet Wahlberg, M Mahafuzur Rahman, Hanna Lindberg, Elin Gunneriusson, Benjamin Schmuck, Christofer Lendel, Mats Sandgren, John Löfblom, Stefan Ståhl, Torleif Härd
Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer's disease. Hence, there is a need for research reagents and potential diagnostic reagents for detection and imaging of such aggregates. Here we describe an in vitro selection of Affibody molecules that bind to protofibrils of Aβ42cc, which is a stable engineered mimic of wild type Aβ42 protofibrils...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728879/identification-of-universal-diagnostic-peptide-candidates-for-neglected-tropical-diseases-caused-by-cestodes-through-the-integration-of-multi-genome-wide-analyses-and-immunoinformatic-predictions
#2
Sebastián Miles, Marco Navatta, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Neglected tropical diseases caused by helminth infections currently affect millions of people worldwide. Among them, there are three tapeworm species of outstanding importance: Echinococcus granulosus, E. multilocularis, and Taenia solium, which are responsible for cystic echinococcosis, alveolar echinococcosis, and cysticercosis, respectively. Despite several attempts, there is still a need for an effective and low-cost serological diagnostic test that can be used in endemic countries. In the present work, we described an innovative bioinformatic workflow for a rational prediction of putative peptide candidates for one-step serological diagnosis of any of these infections...
July 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28726542/generation-and-functional-characterization-of-anti-human-and-anti-mouse-il-36r-antagonist-monoclonal-antibodies
#3
Rajkumar Ganesan, Ernest L Raymond, Detlev Mennerich, Joseph R Woska, Gary Caviness, Christine Grimaldi, Jennifer Ahlberg, Rocio Perez, Simon Roberts, Danlin Yang, Kavita Jerath, Kristopher Truncali, Lee Frego, Eliud Sepulveda, Priyanka Gupta, Su-Ellen Brown, Michael D Howell, Keith A Canada, Rachel Kroe-Barrett, Jay S Fine, Sanjaya Singh, M Lamine Mbow
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP)...
July 20, 2017: MAbs
https://www.readbyqxmd.com/read/28715148/lineage-specific-epitope-profiles-for-hpai-h5-pre-pandemic-vaccine-selection-and-evaluation
#4
Xueting Qiu, Venkata R Duvvuri, Jonathan B Gubbay, Richard Webby, Ghazi Kayali, Justin Bahl
BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co-circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study we aim to predict and map the diversity of CD8+ T-cell epitopes among H5 Hemagglutinin (HA) gene lineages to estimate CD8+ T-cell immunity in humans induced by vaccine candidates. METHODS: A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage-specific epitope analyses...
July 17, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28713960/prediction-and-identification-of-b%C3%A2-cell-epitopes-for-tumor-necrosis-factor%C3%A2-%C3%AE
#5
Jun Zhang, Ying Cui, Yinfang Wu, Huiju Wang, Jinjing Ke
The aim of the present study was to predict and identify B‑cell epitopes for mouse tumor necrosis factor‑α (mTNF‑α). DNAStar and BcePred software were used to predict B‑cell epitopes for mTNF‑α. A predicted eight‑branch multiple antigenic polypeptide (MAP) was synthesized and used to immunize BALB/c mice, combined with a promiscuous helper interleukin‑1β epitope (VQGEESNDK, amino acids 163‑171). The serum titer was measured. The specificity and avidity were determined by western blotting and indirect enzyme‑linked immunosorbent assay (ELISA)...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28708892/cross-recognition-of-a-pit-viper-crotalinae-polyspecific-antivenom-explored-through-high-density-peptide-microarray-epitope-mapping
#6
Mikael Engmark, Bruno Lomonte, José María Gutiérrez, Andreas H Laustsen, Federico De Masi, Mikael R Andersen, Ole Lund
Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations for antivenom cross-reactivity. In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high-throughput methodology based on custom designed high-density peptide microarrays...
July 14, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28704364/dramatic-and-concerted-conformational-changes-enable-rhodocetin-to-block-%C3%AE-2%C3%AE-1-integrin-selectively
#7
Johannes A Eble, Matthew McDougall, George L Orriss, Stephan Niland, Benjamin Johanningmeier, Gottfried Pohlentz, Markus Meier, Simone Karrasch, Maria Inacia Estevão-Costa, Augusto Martins Lima, Jörg Stetefeld
The collagen binding integrin α2β1 plays a crucial role in hemostasis, fibrosis, and cancer progression amongst others. It is specifically inhibited by rhodocetin (RC), a C-type lectin-related protein (CLRP) found in Malayan pit viper (Calloselasma rhodostoma) venom. The structure of RC alone reveals a heterotetramer arranged as an αβ and γδ subunit in a cruciform shape. RC specifically binds to the collagen binding A-domain of the integrin α2 subunit, thereby blocking collagen-induced platelet aggregation...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28702519/bottom-up-hydrogen-deuterium-exchange-mass-spectrometry-data-analysis-and-interpretation
#8
Kerene A Brown, Derek J Wilson
Hydrogen Deuterium Exchange (HDX) Mass Spectrometry (MS) is a sensitive analytical technique that provides information on protein conformation and dynamics in solution. It is commonly used in the study of protein-ligand and protein-protein interactions and more recently in the pharmaceutical industry for epitope mapping, screening drug candidates and in the comparison of biopharmaceuticals to biosimilars. HDX-MS monitors the exchange of protein backbone hydrogen atoms with deuterium in solution. Recent advancements in HDX automation and data analysis, have taken the emphasis off developing a fundamental understanding of HDX, which is still lacking...
July 13, 2017: Analyst
https://www.readbyqxmd.com/read/28699812/epitope-mapping-of-ebola-virus-dominant-and-subdominant-glycoprotein-epitopes-facilitates-construction-of-an-epitope-based-dna-vaccine-able-to-focus-the-antibody-response-in-mice
#9
Daniel A J Mitchell, Lesley C Dupuy, Mariano Sanchez-Lockhart, Gustavo Palacios, Jaap W Back, Katya Shimanovskaya, Sidhartha Chaudhury, Daniel R Ripoll, Anders Wallqvist, Connie S Schmaljohn
We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed two DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP...
July 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28698047/identification-of-a-novel-linear-b-cell-epitope-in-the-p27-of-avian-leukosis-virus
#10
Wiaam O A Khairy, Lin Wang, Xue Tian, Jianqiang Ye, Kun Qian, Hongxia Shao, Aijian Qin
Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can induce virus-associated neoplasia and causes great economic loss in poultry industry. It is known that the capsid antigen p27 is the group-specific antigen that is highly conserved among all ALV subgroups, and is the most abundant immunogenic viral protein. In the present study, five overlapping fragments (GST- p27-F1/2, GST- p27-F2-1/2/3) of ALV-p27 were subjected to Western blotting analysis using a monoclonal antibody (5D3) against ALV-p27 to identify the epitope...
July 8, 2017: Virus Research
https://www.readbyqxmd.com/read/28696188/evolution-of-cross-neutralizing-antibodies-and-mapping-epitope-specificity-in-plasma-of-chronic-hiv-1-infected-antiretroviral-therapy-na%C3%A3-ve-children-from-india
#11
Muzamil A Makhdoomi, Lubina Khan, Sanjeev Kumar, Heena Aggarwal, Ravinder Singh, Rakesh Lodha, Mohit Singla, Bimal K Das, Sushil K Kabra, Kalpana Luthra
Delineating the factors leading to the development of broadly neutralizing antibodies (bnAbs) during natural HIV-1 infection and dissecting their epitope specificities generates useful information for vaccine design. This is the first longitudinal study to assess the plasma-neutralizing antibody response and neutralizing determinants in HIV-1-infected children from India. We enrolled 26 and followed up 20 antiretroviral therapy (ART)-naïve, asymptomatic, chronic HIV-1-infected children. Five (19.2 %) baseline and 10 (50 %) follow-up plasma samples neutralized ≥50 % of subtypes A, B and C tier 2 viruses at an ID50 titre ≥150...
July 12, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28694427/comparative-phylogenetic-analyses-of-recombinant-noroviruses-based-on-different-protein-encoding-regions-show-the-recombination-associated-evolution-pattern
#12
Liang Xue, Qingping Wu, Ruimin Dong, Weicheng Cai, Haoming Wu, Moutong Chen, Gang Chen, Juan Wang, Jumei Zhang
Noroviruses are the major cause of acute gastroenteritis worldwide, and recombination is recognized as the important mechanism for its continuous emergence. In this study, for the common GII.P12 and GII.3 recombinants, phylogenetic relationships based on different proteins in three ORFs were comparatively analyzed, focusing on the influence of intergenic recombination. By using newly designed primers, genomes of two GII.P12/GII.3 Guangzhou recombinants were firstly amplified. Combined with other reported sequences of GII...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28689040/unsupervised-learning-techniques-reveal-heterogeneity-in-memory-cd8-t-cell-differentiation-following-acute-chronic-and-latent-viral-infections
#13
Mingyong Liu, Erik S Barton, Ryan N Jennings, Darby G Oldenburg, Juliann M Whirry, Douglas W White, Jason M Grayson
CD8(+) T lymphocytes are critical for the control of gammaherpesvirus latency. To determine how memory CD8(+) T cells generated during latency differ from those primed during acute or chronic viral infection, we adoptively transferred naive P14 CD8(+) T cells into uninfected recipients, and examined surface proteins, cytokines and transcription factors following infection with the Armstrong (acute) or Clone 13 (chronic) strains of lymphocytic choriomeningitis virus (LCMV), or murine gammaherpesvirus 68 (MHV68) expressing the LCMV epitope D(b)GP33-41...
September 2017: Virology
https://www.readbyqxmd.com/read/28686909/unraveling-the-role-of-maternal-anti-hla-class-i-antibodies-in-fetal-and-neonatal-thrombocytopenia-antibody-specificity-analysis-using-epitope-data
#14
Jesper Dahl, Erle Refsum, Maria Therese Ahlen, Torstein Egeland, Tore Jensen, Marte K Viken, Tor Brynjar Stuge, Ganesh Acharya, Anne Husebekk, Bjørn Skogen, Heidi Tiller
Anti-HLA class I antibodies have been suggested as a possible cause of fetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to characterize maternal anti-HLA class I alloantibodies in suspected cases of FNAIT. The study population consisted of all nationwide referrals of neonates with suspected FNAIT to the National Unit for Platelet Immunology in Tromsø, Norway, during 1998-2009 (cases), and 250 unselected pregnancies originally included in a prospective study (controls). Inclusion criterion was a positive screening for maternal anti-HLA class I antibodies...
June 27, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28686617/dengue-virus-specific-igy-provides-protection-following-lethal-dengue-virus-challenge-and-is-neutralizing-in-the-absence-of-inducing-antibody-dependent-enhancement
#15
Ashley L Fink, Katherine L Williams, Eva Harris, Travis D Alvine, Thomas Henderson, James Schiltz, Matthew L Nilles, David S Bradley
Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28680159/peptides-derived-from-the-knuckle-epitope-of-bmp-9-induce-the-cholinergic-differentiation-and-inactivate-gsk3beta-in-human-sh-sy5y-neuroblastoma-cells
#16
Marc-Antoine Lauzon, Olivier Drevelle, Nathalie Faucheux
The incidence of brain degenerative disorders like Alzheimer's disease (AD) will increase as the world population ages. While there is presently no known cure for AD and current treatments having only a transient effect, an increasing number of publications indicate that growth factors (GF) may be used to treat AD. GFs like the bone morphogenetic proteins (BMPs), especially BMP-9, affect many aspects of AD. However, BMP-9 is a big protein that cannot readily cross the blood-brain barrier. We have therefore studied the effects of two small peptides derived from BMP-9 (pBMP-9 and SpBMP-9)...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678607/hiv-env-conserved-element-dna-vaccine-alters-immunodominance-in-macaques
#17
Xintao Hu, Antonio Valentin, Margherita Rosati, Siriphan Manocheewa, Candido Alicea, Bhabadeb Chowdhury, Jenifer Bear, Kate E Broderick, Niranjan Y Sardesai, Sylvie Le Gall, James I Mullins, George N Pavlakis, Barbara K Felber
Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV. HIV Env is a highly-glycosylated protein composed of 'conserved' and 'variable' regions. The latter contains immunodominant epitopes that are frequently targeted by the immune system resulting in the generation of immune escape variants. This work describes 12 regions in HIV Env that are highly conserved throughout the known HIV M Group sequences (Env CE), and are poorly immunogenic in macaques vaccinated with full-length Env expressing DNA vaccines...
July 5, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28660200/a-fast-and-inexpensive-protocol-for-empirical-verification-of-neutralizing-epitopes-in-microbial-toxins-and-enzymes
#18
Christine N Vuong, Wen-Ko Chou, Vivek A Kuttappan, Billy M Hargis, Lisa R Bielke, Luc R Berghman
In vivo targeting of peptides to antigen-presenting cells by use of agonistic anti-CD40 monoclonal antibodies has been used successfully as an immune response enhancing strategy. When tested in chickens, the antibody-guided platform was capable of inducing specific IgG production within 1 week postimmunization. However, use of this method beyond its initial conception as a vaccine delivery tool has not been fully exploited. In this study, Clostridium perfringens alpha-toxin was used as a model microbial toxin for epitope mapping by using the antibody-guided immunization method to generate a panel of antibodies against specific, regions of the toxin in an attempt to identify crucial determinants on the toxin which, once bound, would hinder downstream toxicity...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28657670/mapping-the-recognition-domains-of-pneumococcal-fibronectin-binding-proteins-pava-and-pavb-demonstrates-a-common-pattern-of-molecular-interactions-with-fibronectin-type-iii-repeats
#19
Sajida Kanwal, Inga Jensch, Gottfried J Palm, Mark Brönstrup, Manfred Rohde, Thomas P Kohler, Daniela Somplatzki, Werner Tegge, Howard F Jenkinson, Sven Hammerschmidt
Colonization of mucosal respiratory surfaces is a prerequisite for the human pathobiont Streptococcus pneumoniae (the pneumococcus) to cause severe invasive infections. The arsenal of pneumococcal adhesins interacts with a multitude of extracellular matrix proteins. A paradigm for pneumococci is their interaction with the adhesive glycoprotein fibronectin, which facilitates bacterial adherence to host cells. Here, we deciphered the molecular interaction between fibronectin and pneumococcal fibronectin-binding proteins (FnBPs) PavA and PavB, respectively...
June 28, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28655344/prevention-of-dendritic-and-synaptic-deficits-and-cognitive-impairment-with-a-neurotrophic-compound
#20
Narjes Baazaoui, Khalid Iqbal
BACKGROUND: The use of neurotrophic factors to treat Alzheimer's disease (AD) is hindered by their blood-brain barrier impermeability, short half-life, and severe side effects. Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood-brain barrier permeability and decrease its degradation by exopeptidases to make it druggable...
June 27, 2017: Alzheimer's Research & Therapy
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