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https://www.readbyqxmd.com/read/29777446/the-degree-of-hiv-1-amino-acid-variability-is-strictly-related-to-different-disease-progression-rates
#1
Rossana Scutari, Monica Faieta, Roberta D'Arrigo, Lavinia Fabeni, Cristina Mussini, Andrea Cossarizza, Claudio Casoli, Carlo Federico Perno, Valentina Svicher, Claudia Alteri, Stefano Aquaro
The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2-V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2)...
May 17, 2018: Virus Genes
https://www.readbyqxmd.com/read/29775667/identification-of-novel-hla-a11-restricted-t-cell-epitopes-in-the-ebola-virus-nucleoprotein
#2
Dan Li, Pei Li, Nianping Song, Yuting Jiang, Yang Zeng, Guangyu Zhao, Yunzhi Fa, Huahu Ye, Yuchun Lone, Yusen Zhou, Shihui Sun, Lin Zeng
The Ebola virus (EBOV) is a very contagious virus that is highly fatal in humans and animals. The largest epidemic was in West Africa in 2014, in which over 11,000 people died. However, to date, there are no licensed vaccines against it. Studies show that CD4+ and CD8+ T-cell responses, especially cytotoxic T-lymphocyte (CTL) responses, play key roles in protecting individuals from EBOV infection. Since HLA-restricted epitope vaccines are likely to be effective and safe immunization strategies for infectious diseases, the present study screened for CTL epitopes in the EBOV-nucleoprotein that are restricted by HLA-A11 (a common allele in Chinese people)...
May 15, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29774024/quantification-of-hla-dm-dependent-major-histocompatibility-complex-of-class-ii-immunopeptidomes-by-the-peptide-landscape-antigenic-epitope-alignment-utility
#3
Miguel Álvaro-Benito, Eliot Morrison, Esam T Abualrous, Benno Kuropka, Christian Freund
The major histocompatibility complex of class II (MHCII) immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773099/-toxoplasma-gondii-rop38-promotes-the-maturation-of-dendritic-cells-mediated-by-tlr4
#4
Heng Zhang, Shanghua Wu, Zhiqiang Shi, Shan Wang, Wei Lu, Yizhen Wu, Pei Sun, Qianming Xu
Objective To investigate the effect of rhoptry protein 38 (ROP38) from Toxoplasma gondii (T. gondii) on the maturation of dendritic cells (DCs) by Toll-like receptor 4 (TLR4) induction in vitro. Methods The total RNA from T. gondii RH strain was extracted by guanidine thiocyanate method, and then cDNA was synthesized with reverse transcription reaction. After ROP38 gene was amplified by PCR, the recombinant pGEX-4T-ROP38 was constructed and expressed under IPTG induction. The recombinant ROP38 protein was detected by SDS-PAGE and Western blot analysis...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29772544/antigen-specific-therapy-of-graves%C3%A2-disease-and-orbitopathy-by-induction-of-tolerance
#5
Martin Ungerer, Julia Fabbender, Hans-Peter Holthoff
Graves´ disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. The disease can be modelled in mice using adenoviral immunizations with the extracellular A subunit of the TSHR, which induces a long-term stable disease state. TSHR binding cAMP-stimulatory antibodies, thyroid enlargement, elevated serum thyroxin levels, tachycardia, cardiac hypertrophy and orbitopathy are observed in these Ad-TSHR-immunized mice...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772075/cd6-mabs-differ-in-epitope-kinetics-and-mechanism-of-action
#6
Lee I Garner, Andrew Hartland, Johannes Breuning, Marion H Brown
CD6 is a type I T cell surface receptor which modulates antigen receptor signalling. Its activity is regulated by binding of its membrane proximal domain (domain 3) to a cell surface ligand, CD166. CD6 monoclonal antibodies (mAbs) specific for the membrane distal domain (domain 1) perturb CD6 function including itolizumab (Alzumab™ ) which has reached the clinic for treatment of autoimmune disease. We characterised molecular and functional properties of several CD6 mAbs including itolizumab to define potential mechanisms of action...
May 17, 2018: Immunology
https://www.readbyqxmd.com/read/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#7
Nicola J Borthwick, Thirusha Lane, Nathifa Moyo, Alison Crook, Jung Min Shim, Ian Baines, Edmund G Wee, Philip N Hawkins, Julian D Gillmore, Tomáš Hanke, Mark B Pepys
BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%...
2018: PloS One
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#8
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29769722/bystander-cd8-t-cells-are-abundant-and-phenotypically-distinct-in-human-tumour-infiltrates
#9
Yannick Simoni, Etienne Becht, Michael Fehlings, Chiew Yee Loh, Si-Lin Koo, Karen Wei Weng Teng, Joe Poh Sheng Yeong, Rahul Nahar, Tong Zhang, Hassen Kared, Kaibo Duan, Nicholas Ang, Michael Poidinger, Yin Yeng Lee, Anis Larbi, Alexis J Khng, Emile Tan, Cherylin Fu, Ronnie Mathew, Melissa Teo, Wan Teck Lim, Chee Keong Toh, Boon-Hean Ong, Tina Koh, Axel M Hillmer, Angela Takano, Tony Kiat Hon Lim, Eng Huat Tan, Weiwei Zhai, Daniel S W Tan, Iain Beehuat Tan, Evan W Newell
Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4 . Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6 . Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10 , in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769533/structure-of-a-cleavage-independent-hiv-env-recapitulates-the-glycoprotein-architecture-of-the-native-cleaved-trimer
#10
Anita Sarkar, Shridhar Bale, Anna-Janina Behrens, Sonu Kumar, Shailendra Kumar Sharma, Natalia de Val, Jesper Pallesen, Adriana Irimia, Devan C Diwanji, Robyn L Stanfield, Andrew B Ward, Max Crispin, Richard T Wyatt, Ian A Wilson
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769329/isolation-of-state-dependent-monoclonal-antibodies-against-the-12-transmembrane-domain-glucose-transporter-4-using-virus-like-particles
#11
David F Tucker, Jonathan T Sullivan, Kimberly-Anne Mattia, Christine R Fisher, Trevor Barnes, Manu N Mabila, Rona Wilf, Chidananda Sulli, Meghan Pitts, Riley J Payne, Moniquetta Hall, Duncan Huston-Paterson, Xiaoxiang Deng, Edgar Davidson, Sharon H Willis, Benjamin J Doranz, Ross Chambers, Joseph B Rucker
The insulin-responsive 12-transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational mAbs against complex and highly conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking, or detect the conformational state of the protein. Here we report the isolation and characterization of conformational mAbs that recognize the extracellular and intracellular domains of GLUT4, including mAbs that are specific for the inward-open and outward-open states of GLUT4...
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29768704/syntheses-and-immunological-evaluation-of-self-adjuvanting-clustered-n-acetyl-and-n-propionyl-sialyl-tn-combined-with-a-t-helper-cell-epitope-as-antitumor-vaccine-candidates
#12
Tsung-Che Chang, Yoshiyuki Manabe, Yukari Fujimoto, Shino Ohshima, Yoshie Kametani, Kazuya Kabayama, Yuka Nimura, Chun-Cheng Lin, Koichi Fukase
Sialyl-Tn (STn) is a tumor-associated carbohydrate antigen (TACA) rarely observed on healthy tissues. We synthesized two fully synthetic N-acetyl and N-propionyl STn trimer (triSTn) vaccines possessing a T-helper epitope and a TLR2 agonist, since the clustered STn antigens are highly expressed on many cancer cells. Immunization of both vaccines in mice induced the anti-triSTn IgG antibodies, which recognized triSTn-expressing cell lines PANC-1 and HepG2. The N-propionyl triSTn vaccine induced the triSTn-specific IgGs, while IgGs induced by the N-acetyl triSTn vaccine were less specific...
May 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29765561/a-pilot-study-of-peptide-vaccines-for-vegf-receptor-1-and-2-in-patients-with-recurrent-progressive-high-grade-glioma
#13
Shunsuke Shibao, Ryo Ueda, Katsuya Saito, Ryogo Kikuchi, Hideaki Nagashima, Atsuhiro Kojima, Hiroshi Kagami, Eriel Sandika Pareira, Hikaru Sasaki, Shinobu Noji, Yutaka Kawakami, Kazunari Yoshida, Masahiro Toda
Object: Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764836/subcellular-localization-of-antigen-dictates-delivery-of-cd4-t-cell-help-for-the-ctl-response-upon-therapeutic-dna-vaccination-into-the-skin
#14
Nikolina Bąbała, Astrid Bovens, Evert de Vries, Victoria Iglesias-Guimarais, Tomasz Ahrends, Matthew F Krummel, Jannie Borst, Adriaan D Bins
In a mouse model of therapeutic DNA vaccination, we studied how the subcellular localization of vaccine protein impacts antigen delivery to professional antigen presenting cells (pAPCs) and efficiency of CTL priming. Cytosolic, membrane-bound, nuclear, and secretory versions of ZsGreen fluorescent protein, conjugated to MHC class I and -II ovalbumin (OVA) epitopes were expressed in keratinocytes by DNA vaccination into the skin. ZsGreen-OVA versions reached B cells in the skin-draining lymph node (dLN) that proved irrelevant for CTL priming...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29763778/mage-a-antigens-as-targets-for-cancer-immunotherapy
#15
REVIEW
Erik Schooten, Alessia Di Maggio, Paul M P van Bergen En Henegouwen, Marta M Kijanka
Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies...
April 26, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29760216/-plasmodium-falciparum-msp3-exists-in-a-complex-on-the-merozoite-surface-and-generates-antibody-response-during-natural-infection
#16
Arunaditya Deshmukh, Bishwanath Kumar Chourasia, Sonali Mehrotra, Ikhlaq Hussain Kana, Gourab Paul, Ashutosh Panda, Inderjeet Kaur, Susheel Kumar Singh, Sumit Rathore, Aparup Das, Priya Gupta, Kalamuddin Md, S K Ghakar, Asif Mohmmed, Michael Theisen, Pawan Malhotra
Plasmodium falciparum merozoite surface protein 3 (MSP3) is an abundantly expressed secreted merozoite surface protein and a leading malaria vaccine candidate antigen. However, it is unclear how MSP3 is retained on the surface of merozoites without a GPI anchor or a transmembrane domain. In the present study, we identified an MSP3 associated network on the Plasmodium merozoite surface by Immunoprecipitation of Plasmodium merozoite lysate using anti-MSP3N antibodies followed by mass spectrometry analysis. The results suggested the association of MSP3 with other merozoite surface proteins; MSP1, MSP6, MSP7, RAP2 and SERA5...
May 14, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29755478/the-contribution-of-autoantibodies-to-inflammatory-cardiovascular-pathology
#17
REVIEW
Lee A Meier, Bryce A Binstadt
Chronic inflammation and resulting tissue damage underlie the vast majority of acquired cardiovascular disease (CVD), a general term encompassing a widely diverse array of conditions. Both innate and adaptive immune mechanisms contribute to chronic inflammation in CVD. Although maladies, such as atherosclerosis and cardiac fibrosis, are commonly conceptualized as disorders of inflammation, the cellular and molecular mechanisms that promote inflammation during the natural history of these diseases in human patients are not fully defined...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755469/urinary-peptides-as-a-novel-source-of-t-cell-allergen-epitopes
#18
Ricardo da Silva Antunes, John Pham, Curtis McMurtrey, William H Hildebrand, Elizabeth Phillips, Simon Mallal, John Sidney, Paula Busse, Bjoern Peters, Véronique Schulten, Alessandro Sette
Mouse allergy in both laboratory workers and in inner-city children is associated with allergic rhinitis and asthma, posing a serious public health concern. Urine is a major source of mouse allergens, as mice spray urine onto their surroundings, where the proteins dry up and become airborne on dust particles. Here, we tested whether oligopeptides that are abundant in mouse urine may contribute to mouse allergic T cell response. Over 1,300 distinct oligopeptides were detected by mass spectrometry analysis of the low molecular weight filtrate fraction of mouse urine (LoMo)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755468/approaches-to-improve-chemically-defined-synthetic-peptide-vaccines
#19
REVIEW
Brett J Hos, Elena Tondini, Sander I van Kasteren, Ferry Ossendorp
Progress made in peptide-based vaccinations to induce T-cell-dependent immune responses against cancer has invigorated the search for optimal vaccine modalities. Design of new vaccine strategies intrinsically depends on the knowledge of antigen handling and optimal epitope presentation in both major histocompatibility complex class I and -II molecules by professional antigen-presenting cells to induce robust CD8 and CD4 T-cell responses. Although there is a steady increase in the understanding of the underlying mechanisms that bridges innate and adaptive immunology, many questions remain to be answered...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754509/-new-and-traditional-directions-in-the-biology-and-management-of-childhood-acute-lymphoblastic-leukemia
#20
Bálint Egyed, Gábor Kovács, Nóra Kutszegi, Andrea Rzepiel, Judit Csányiné Sági, Dániel János Erdélyi, Judit Müller, Ágnes Félné Semsei
Owing to clinical trials and improvement over the past few decades, the majority of children with acute lymphoblastic leukemia (ALL) survive by first-line chemotherapy and combat with the problems of returning to community. However, many patients may have severe acute or late therapeutic side effects, and the survival rate in some groups (e.g., patients with MLL rearrangements, hypodiploidy, IKZF1 mutation or early precursor T cell phenotype) is far behind the average. Innovative strategies in medical attendance provide better clinical outcomes for them: complete gene diagnostics, molecularly targeted anticancer treatment, immuno-oncology and immune cell therapy...
May 2018: Orvosi Hetilap
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