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Epitope mapping

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https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#1
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29135227/peptide-arrays-development-and-application
#2
Lindsey Szymczak, Hsin-Yu Kuo, Milan Mrksich
Peptide arrays are an exciting and rapidly growing technology with a broad range of applications in the basic and applied life sciences. Peptide arrays have been under development for approximately twenty-five years, and commercial versions have been available for the past decade. The arrays typically comprise hundreds to thousands of distinct peptide sequences, and have proven important for determining substrate specificities of enzymes, profiling antibodies and mapping epitopes, studying ligand-receptor interactions and identifying ligands that mediate cell adhesion...
November 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29128919/genome-wide-prediction-of-potential-vaccine-candidates-for-campylobacter-jejuni-using-reverse-vaccinology
#3
Richa Jain, Sarita Singh, Santosh Kumar Verma, Ankit Jain
Campylobacteriosis is a deadly disease which has developed resistance to most of the available chemotherapeutic agents. Although various studies provide evidence of acquired immunity following exposure to Campylobacter jejuni, no effective vaccine has been developed, still. Hence, there is an urgent need to identify potential vaccine candidates for Campylobacter species. In the proposed study, Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168) was taken and computational approach was employed to screen C...
November 11, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/29128754/development-and-characterization-of-a-human-monoclonal-antibody-targeting-the-n-terminal-region-of-hepatitis-c-virus-envelope-glycoprotein-e1
#4
Ahmed Atef Mesalam, Isabelle Desombere, Ali Farhoudi, Freya Van Houtte, Lieven Verhoye, Jonathan Ball, Jean Dubuisson, Steven K H Foung, Arvind H Patel, Mats A A Persson, Geert Leroux-Roels, Philip Meuleman
Monoclonal antibodies (mAbs) targeting the hepatitis C virus (HCV) envelope have been raised mainly against envelope protein 2 (E2), while the antigenic epitopes of envelope protein 1 (E1) are not fully identified. Here we describe the detailed characterization of a human mAb, designated A6, generated from an HCV genotype 1b infected patient. ELISA results showed reactivity of mAb A6 to full-length HCV E1E2 of genotypes 1a, 1b and 2a. Epitope mapping identified a region spanning amino acids 230-239 within the N-terminal region of E1 as critical for binding...
November 9, 2017: Virology
https://www.readbyqxmd.com/read/29128334/a-map-of-human-mitochondrial-protein-interactions-linked-to-neurodegeneration-reveals-new-mechanisms-of-redox-homeostasis-and-nf-%C3%AE%C2%BAb-signaling
#5
Ramy H Malty, Hiroyuki Aoki, Ashwani Kumar, Sadhna Phanse, Shahreen Amin, Qingzhou Zhang, Zoran Minic, Florian Goebels, Gabriel Musso, Zhuoran Wu, Hosam Abou-Tok, Michael Meyer, Viktor Deineko, Sandy Kassir, Vishaldeep Sidhu, Matthew Jessulat, Nichollas E Scott, Xuejian Xiong, James Vlasblom, Bhanu Prasad, Leonard J Foster, Tiziana Alberio, Barbara Garavaglia, Haiyuan Yu, Gary D Bader, Ken Nakamura, John Parkinson, Mohan Babu
Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs); however, the discovery of the molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using mass spectrometry (MS)-based analysis of 210 affinity-purified mitochondrial (mt) fractions isolated from 27 epitope-tagged human ND-linked MPs in HEK293 cells, we report a high-confidence MP network including 1,964 interactions among 772 proteins (>90% previously unreported)...
November 7, 2017: Cell Systems
https://www.readbyqxmd.com/read/29125554/antibody-competition-reveals-surface-location-of-hpv-l2-minor-capsid-protein-residues-17-36
#6
Stephanie M Bywaters, Sarah A Brendle, Kerstin P Tossi, Jennifer Biryukov, Craig Meyers, Neil D Christensen
The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion...
November 10, 2017: Viruses
https://www.readbyqxmd.com/read/29121407/strong-and-frequent-t-cell-responses-to-the-minor-allergen-phl-p-12-in-spanish-patients-ige-sensitized-to-profilins
#7
Gitte Lund, Stephanie Brand, Tania Ramos, Lucia Jimeno, Patrice Boissy, Francisco Vega, Maria Arina, Lars Harder Christensen, Ilka Hoof, Kåre Hvalsøe Meno, Domingo Barber, Carlos Blanco, Peter Adler Würtzen, Peter Sejer Andersen
BACKGROUND: Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as the pollen food syndrome. This study aims to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins. METHODS: The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2, and Mal d 4) were measured in-vitro using PBMCs from 26 Spanish grass allergic donors IgE-sensitized to profilin...
November 9, 2017: Allergy
https://www.readbyqxmd.com/read/29120697/enhancing-antibody-patent-protection-using-epitope-mapping-information
#8
Xiaoxiang Deng, Ulrich Storz, Benjamin J Doranz
As the $100B therapeutic monoclonal antibody (mAb) market continues to grow, developers of therapeutic mAbs increasingly face the need to strengthen patent protection of their products and enforce their patents in courts. In view of changes in the patent law landscape, patent applications are strategically using information on the precise binding sites of their mAbs, i.e., the epitopes, to support patent novelty, non-obviousness, subject matter, and a tightened written description requirement for broad genus antibody claims...
November 9, 2017: MAbs
https://www.readbyqxmd.com/read/29120180/synthesis-and-application-of-branched-type-ii-arabinogalactans
#9
Mathias C F Andersen, Irene Boos, Colin Ruprecht, William G T Willats, Fabian Pfrengle, Mads Hartvig Clausen
The synthesis of linear- and (1→6)-branched β-(1→3)-D-galactans, structures found in plant arabinogalactan proteins (AGPs) is described. The synthetic strategy relies on iterative couplings of mono- and disaccharide thioglycoside donors, followed by a late stage glycosylation of heptagalactan backbone acceptors to introduce branching. A key finding from the synthetic study was the need to match protective groups in order to tune reactivity and ensure selectivity during the assem-bly. Carbohydrate microarrays were generated to enable the detailed epitope mapping of two monoclonal antibodies known to recognize AGPs: JIM16 and JIM133...
November 9, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29119120/computer-aided-design-of-an-epitope-based-vaccine-against-epstein-barr-virus
#10
Julio Alonso-Padilla, Esther M Lafuente, Pedro A Reche
Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt's lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29116524/epitope-mapping-by-phage-display
#11
Gustavo Marçal Schmidt Garcia Moreira, Viola Fühner, Michael Hust
Among the molecules of the immune system, antibodies, particularly monoclonal antibodies (mAbs), have been shown to be interesting for many biological applications. Due to their ability to recognize only a unique part of their target, mAbs are usually very specific. These targets can have many different compositions, but the most common ones are proteins or peptides that are usually from outside the host, although self-proteins can also be targeted in autoimmune diseases, or in some types of cancer. The parts of a mAb that interact with its target compose the paratope, while the recognized parts of the target compose the epitope...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29107699/synthetic-three-component-hiv-1-v3-glycopeptide-immunogens-induce-glycan-dependent-antibody-responses
#12
Hui Cai, Jared Orwenyo, John P Giddens, Qiang Yang, Roushu Zhang, Celia C LaBranche, David C Montefiori, Lai-Xi Wang
Eliciting broadly neutralizing antibody (bNAb) responses against HIV-1 is a major goal for a prophylactic HIV-1 vaccine. One approach is to design immunogens based on known broadly neutralizing epitopes. Here we report the design and synthesis of an HIV-1 glycopeptide immunogen derived from the V3 domain. We performed glycopeptide epitope mapping to determine the minimal glycopeptide sequence as the epitope of V3-glycan-specific bNAbs PGT128 and 10-1074. We further constructed a self-adjuvant three-component immunogen that consists of a 33-mer V3 glycopeptide epitope, a universal T helper epitope P30, and a lipopeptide (Pam3CSK4) that serves as a ligand of Toll-like receptor 2...
October 4, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29107382/human-monoclonal-antibodies-neutralizing-influenza-virus-a-h1n1pdm09-and-seasonal-a-h1n1-strains-distinct-ig-gene-repertoires-with-a-similar-action-mechanism
#13
Satoshi Hiroi, Motoki Kuhara, Yoshiro Kishi, Ken-Ichiro Ono, Shun Matsuzawa, Naomasa Yamamoto, Jun Komano
Influenza virus causes acute respiratory infection in humans, and is a major public health concern globally. Antibodies play a central role in host protection against influenza virus. We isolated human monoclonal antibodies (hMAb) 206-2-4 and 201-6-8 by a human hybridoma protocol that neutralized various but distinct influenza virus (IFV) A/H1N1 strains, including 2009 pandemic strains. The half-inhibitory concentration of 206-2-4 and 201-6-8 against A/H1N1pdm09 strains was 2-100ng/mL and 5-20μg/mL, respectively...
October 18, 2017: Immunobiology
https://www.readbyqxmd.com/read/29103692/identification-of-b-cell-linear-epitopes-in-domains-1-3-of-pyolysin-of-trueperella-pyogenes-using-polyclonal-antibodies
#14
Lingxiao Yang, Yue Zhang, Haili Wang, Bo Ma, Li Xu, Junwei Wang, Wenlong Zhang
Trueperella pyogenes is an important opportunistic pathogen. Pyolysin (PLO) makes important contributions to the pathogenicity of T. pyogenes. However, the structure and function of PLO has not been well documented. In the current study, epitopes in domain 1-3 of PLO have been mapped using rabbit anti-recombinant PLO (rPLO) polyclonal antibodies, and then the results were re-checked by using mouse and chicken anti-rPLO polyclonal antibodies, respectively. The results indicated that the region of aa 281-393 in PLO could not elicit antibodies against linear epitopes...
October 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29102126/development-of-cdv-specific-monoclonal-antibodies-for-differentiation-of-variable-epitopes-of-nucleocapsid-protein
#15
Zhenwei Bi, Yongshan Wang, Qunxing Pan, Xingxia Xia, Libo Xu
The highly contagious canine distemper viruses (CDVs) are still a major threat to a wide range of natural susceptible hosts. The nucleocapsid (N) protein plays various roles in the virus-induced immune response. But precise mapping of epitopes and antigenic variations in N protein of CDV are still scant. In this study, two monoclonal antibodies (MAbs), designated as F8N and G3N, against the N protein of CDV were generated and characterized. The epitopes recognized by the two MAbs were mapped by truncated N protein fragments expressed in E...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29102104/identification-of-two-conserved-b-cell-epitopes-in-the-gp90-of-reticuloendothelial-virus-using-peptide-microarray
#16
Wiaam O A Khairy, Kun Qian, Hongxia Shao, Jianqiang Ye, Aijian Qin
Since the gp90 protein of Reticuloendotheliosis virus (REV) plays vital roles in virus neutralization, so detailed analysis of REV-gp90 epitopes is important for the development of epitope based marker vaccines and diagnostic tools for REV infections. In this study, two monoclonal antibodies (mAbs) namely 6C12 and 09980 were used to map the epitopes in REVgp90 using peptide microarray and ELISA. Peptide microarray revealed that mAbs 6C12 and 09980 recognized (216)YHPLA(220) and (230)DPQTSDILEA(239) motifs, respectively...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29096381/epitopes-based-drug-design-for-dengue-virus-envelope-protein-a-computational-approach
#17
Abdul Wadood, Aamir Mehmood, Huma Khan, Muhammad Ilyas, Ayaz Ahmad, Mohammed Alarjah, Tareq Abu-Izneid
Dengue virus (DENV) has emerged as a rapidly spreading epidemic throughout the tropical and subtropical regions around the globe. No suitable drug has been designed yet to fight against DENV, therefore, the need for safe and effective antiviral drug has become imperative. The envelope protein of DENV is responsible for mediating the fusion process between viral and host membranes. This work reports an in silico approach to target B and T cell epitopes for dengue envelope protein inhibition. A conserved region "QHGTI" in B and T cell epitopes of dengue envelope glycoprotein was confirmed to be valid for targeting by visualizing its interactions with the host cell membrane TIM-1 protein which acts as a receptor for serotype 2 and 3...
October 20, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29093091/a-3-0-angstrom-resolution-cryo-electron-microscopy-structure-and-antigenic-sites-of-coxsackievirus-a6-like-particles
#18
Jinhuan Chen, Chao Zhang, Yu Zhou, Xiang Zhang, Chaoyun Shen, Xiaohua Ye, Wen Jiang, Zhong Huang, Yao Cong
Coxsackievirus A6 (CVA6) has recently emerged as one of the predominant causative agents of hand, foot, and mouth disease (HFMD). Structure of CVA6 mature viral particle has not been solved thus far. Our previous work shows that recombinant virus-like particles (VLPs) of CVA6 represent a promising CVA6 vaccine candidate. Here, we report the first cryo-electron microscopy (cryo-EM) structure of CVA6 VLP at 3.0 Å resolution. CVA6 VLP exhibits the characteristic features of enteroviruses, but presents an open channel at the two-fold axis and an empty, collapsed VP1 pocket, which is broadly similar to the structures of enterovirus 71 (EV71) VLP and coxsackievirus A16 (CVA16) 135S expanded particle, indicating that CVA6 VLP is in an expanded conformation...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29091453/stubex-plus-a-modified-stable-tagged-ubiquitin-exchange-system-for-peptide-level-purification-and-in-depth-mapping-of-ubiquitination-sites
#19
Vyacheslav Akimov, Louise C B Olsen, Sten V F Hansen, Inigo Barrio-Hernandez, Michele Puglia, Søren S Jensen, Ilia A Solov'yov, Irina Kratchmarova, Blagoy Blagoev
Modulation of protein activities by reversible post-translational modifications (PTMs) is a major molecular mechanism involved in the control of virtually all cellular processes. One of these PTMs is ubiquitination, which regulates key processes including protein degradation, cell cycle, DNA damage repair, and signal transduction. Because of its importance for numerous cellular functions, ubiquitination has become an intense topic of research in recent years, and proteomics tools have greatly facilitated the identification of many ubiquitination targets...
November 1, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29090272/a-new-panel-of-epitope-mapped-monoclonal-antibodies-recognising-the-prototypical-tetraspanin-cd81
#20
Joe Grove, Ke Hu, Michelle J Farquhar, Margaret Goodall, Lucas Walker, Mohammed Jamshad, Heidi E Drummer, Roslyn M Bill, Peter Balfe, Jane A McKeating
Background: Tetraspanins are small transmembrane proteins, found in all higher eukaryotes, that compartmentalize cellular membranes through interactions with partner proteins. CD81 is a prototypical tetraspanin and contributes to numerous physiological and pathological processes, including acting as a critical entry receptor for hepatitis C virus (HCV). Antibody engagement of tetraspanins can induce a variety of effects, including actin cytoskeletal rearrangements, activation of MAPK-ERK signaling and cell migration...
2017: Wellcome Open Research
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