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https://www.readbyqxmd.com/read/28738289/germinal-center-enhancement-by-extended-antigen-availability
#1
REVIEW
Kimberly M Cirelli, Shane Crotty
Vaccine elicitation of protective antibody responses has proved difficult for a number of important human pathogens, including HIV-1. The amount of somatic hypermutation associated with the development of broadly neutralizing antibodies against HIV has not been achieved using conventional immunization strategies. An underexplored aspect of vaccine design is modulation of antigen kinetics. Immunization strategies with extended antigen availability have recently been shown to enhance humoral responses. In this review, we explore the mechanisms through which sustained antigen availability can enhance germinal center responses and the potency of antibody responses...
July 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28735348/analysis-of-the-cd8-t-cell-anti-hiv-activity-in-heterologous-cell-co-cultures-reveals-the-benefit-of-multiple-hla-class-i-matches
#2
M Scott Killian, Fernando Teque, Ramu Sudhagoni
CD8(+) T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4(+) T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8(+) T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4(+) T cells. Altogether, CD8(+) T cell anti-HIV activity was evaluated in more than 200 co-cultures...
July 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28734730/multifaceted-c-x-c-chemokine-receptor-4-inhibition-interferes-with-anti-vascular-endothelial-growth-factor-therapy-induced-glioma-dissemination
#3
Jean-Pierre Gagner, Yasmeen Sarfraz, Valerio Ortenzi, Fawaz M Alotaibi, Luis A Chiriboga, Awab T Tayyib, Garry J Douglas, Eric Chevalier, Barbara Romagnoli, Gérald Tuffin, Michel Schmitt, Guillaume Lemercier, Klaus Dembowsky, David Zagzag
Resistance to antiangiogenic therapy glioblastoma (GBM) patients may involve hypoxia-induced expression of stromal cell-derived factor (SDF)-1α receptor C-X-C chemokine receptor 4 (CXCR4) on invading tumor, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with peptide epitope mimetic POL5551 disrupts anti-vascular endothelial growth factor therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-vascular endothelial growth factor antibody B20-4...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734175/cd8-t-cell-programming-by-cytomegalovirus-vectors-applications-in-prophylactic-and-therapeutic-vaccination
#4
REVIEW
Klaus Früh, Louis Picker
Vectors based on cytomegalovirus (CMV) represent a novel vaccine platform that maintains high frequencies of non-exhausted effector memory T cells in both CMV sero-positive and sero-negative individuals. In non-human primate models, CMV vectored vaccines provide unprecedented protection against simian immunodeficiency virus (SIV). Moreover, CMV vectors can be genetically altered to program highly diverse CD8+ T cell responses that differ in their epitope targeting including conventional, MHC-I restricted CD8+ T cells as well as unconventional CD8+ T cells restricted by MHC class II or non-polymorphic MHC-E...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28733878/role-of-tgf-%C3%AE-in-self-peptide-regulation-of-autoimmunity
#5
REVIEW
Bhagirath Singh, Michael D Krawetz, Rachel M De Lima, Rinee Mukherjee, Pratibha Chaturvedi, Edwin Lee-Chan, Edward H Leiter, Kelly L Summers
Transforming growth factor (TGF)-β has been implicated in regulation of the immune system, including autoimmunity. We have found that TGF-β is readily produced by T cells following immunization with self-peptide epitopes that downregulate autoimmune responses in type 1 diabetes (T1D) prone nonobese diabetic (NOD) mice. These include multiple peptide epitopes derived from the islet β-cell antigens GAD65 (GAD65 p202-221, GAD65 p217-236), GAD67 (GAD67 p210-229, GAD67 p225-244), IGRP (IGRP p123-145, IGRP p195-214) and insulin B-chain (Ins...
July 21, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#6
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730155/surveillance-study-of-influenza-occurrence-and-immunity-in-a-wisconsin-cohort-during-the-2009-pandemic
#7
Chia-Yun Lo, Susan L Strobl, Kimberly Dunham, Wei Wang, Lucy Stewart, Julia A Misplon, Mayra Garcia, Jin Gao, Tatsuhiko Ozawa, Graeme E Price, Jose Navidad, Steve Gradus, Sanjib Bhattacharyya, Cecile Viboud, Maryna C Eichelberger, Carol D Weiss, Jack Gorski, Suzanne L Epstein
BACKGROUND: Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains. Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial. The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28729867/exposure-to-the-epstein-barr-viral-antigen-latent-membrane-protein-1-induces-myelin-reactive-antibodies-in-vivo
#8
Yakov Lomakin, Georgii Pavlovich Arapidi, Alexander Chernov, Rustam Ziganshin, Evgenii Tcyganov, Irina Lyadova, Ivan Olegovich Butenko, Maria Osetrova, Natalia Ponomarenko, Georgy Telegin, Vadim Markovich Govorun, Alexander Gabibov, Alexey Belogurov
Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo...
2017: Frontiers in Immunology
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
#9
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/28727933/genotype-specific-acquisition-evolution-and-adaptation-of-characteristic-mutations-in-hepatitis-e-virus
#10
Aqsa Ikram, Mohamad S Hakim, Jian-Hua Zhou, Wenshi Wang, Maikel P Peppelenbosch, Qiuwei Pan
Hepatitis E virus (HEV) infection is a major cause of acute hepatitis but also provokes chronic infection in immunocompromised patients. Although the pathogenesis and treatment outcome involve complex interplay between the virus and host, the nature of adaptive responses of HEV to the host immune system remain obscure at best. In this study, we employed large-scale proteomic bioinformatics to profile characteristic mutations in human HEV isolates associated to ribavirin treatment failure, chronic hepatitis, hepatic failure or altered immunoreactivity...
July 20, 2017: Virulence
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#11
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28720097/a-versatile-papaya-mosaic-virus-papmv-vaccine-platform-based-on-sortase-mediated-antigen-coupling
#12
Ariane Thérien, Mikaël Bédard, Damien Carignan, Gervais Rioux, Louis Gauthier-Landry, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Pierre Savard, Denis Leclerc
BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide...
July 18, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28715455/synthetic-melanin-bound-to-subunit-vaccine-antigens-significantly-enhances-cd8-t-cell-responses
#13
Antoine F Carpentier, Frédéric Geinguenaud, Thi Tran, Floraly Sejalon, Antoine Martin, Laurence Motte, Eric Tartour, Claire Banissi
Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28715148/lineage-specific-epitope-profiles-for-hpai-h5-pre-pandemic-vaccine-selection-and-evaluation
#14
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/28714529/immunologic-responses-to-a-novel-dna-vaccine-targeting-human-papillomavirus-11-e6e7
#15
Julie Ahn, Shiwen Peng, Chien-Fu Hung, Richard B S Roden, Tzyy-Choou Wu, Simon R Best
OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus (HPV) types 6 and 11. Although a prophylactic vaccine against RRP is available, a therapeutic vaccine is needed to treat those already infected. The objective of our study was to design and test a DNA vaccine targeting HPV11 proteins. STUDY DESIGN: Preclinical scientific investigation. METHODS: A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated...
July 17, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28714174/immunological-properties-and-protective-efficacy-of-a-single-mycobacterial-antigen-displayed-on-polyhydroxybutyrate-beads
#16
Patricia Rubio-Reyes, Natalie A Parlane, Bryce M Buddle, D Neil Wedlock, Bernd H A Rehm
In 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co-delivering either Cpe30 (immunostimulatory peptide), CS.T3378-395 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents...
July 17, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28712768/neutralizing-antibodies-against-a-specific-human-immunodeficiency-virus-gp41-epitope-are-associated-with-long-term-non-progressor-status
#17
Olivier Lucar, Bin Su, Valérie Potard, Assia Samri, Brigitte Autran, Christiane Moog, Patrice Debré, Vincent Vieillard
Antibodies (Abs) play a central role in human immunodeficiency virus (HIV) protection due to their multiple functional inhibitory activities. W614A-3S Abs recognize a specific form of a highly conserved motif of the gp41 envelope protein and can elicit viral neutralization to protect CD4(+) T cells. Here, we describe in detail the neutralizing profile of W614A-3S Abs in untreated long-term non-progressor (LTNP) HIV-infected patients. W614A-3S Abs were detected in 23.5% (16/68) of untreated LTNP patients compared with <5% (5/104) of HIV-1 progressor patients...
July 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28711866/identification-of-apob-100-peptide-specific-cd8-t-cells-in-atherosclerosis
#18
Paul C Dimayuga, Xiaoning Zhao, Juliana Yano, Wai Man Lio, Jianchang Zhou, Peter M Mihailovic, Bojan Cercek, Prediman K Shah, Kuang-Yuh Chyu
BACKGROUND: T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis. METHODS AND RESULTS: A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2K(b) was used to generate a fluorescent-labeled H2K(b) pentamer and tested in apoE(-/-) mice...
July 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28709804/identification-of-natural-regulatory-t-cell-epitopes-reveals-convergence-on-a-dominant-autoantigen
#19
John D Leonard, Dana C Gilmore, Thamotharampillai Dileepan, Wioletta I Nawrocka, Jaime L Chao, Mary H Schoenbach, Marc K Jenkins, Erin J Adams, Peter A Savage
Regulatory T (Treg) cells expressing the transcription factor Foxp3 are critical for the prevention of autoimmunity and the suppression of anti-tumor immunity. The major self-antigens recognized by Treg cells remain undefined, representing a substantial barrier to the understanding of immune regulation. Here, we have identified natural Treg cell ligands in mice. We found that two recurrent Treg cell clones, one prevalent in prostate tumors and the other associated with prostatic autoimmune lesions, recognized distinct non-overlapping MHC-class-II-restricted peptides derived from the same prostate-specific protein...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28705615/transcutaneous-immunotherapy-of-pollinosis-using-solid-in-oil-nanodispersions-loaded-with-t-cell-epitope-peptides
#20
Qingliang Kong, Momoko Kitaoka, Rie Wakabayashi, Noriho Kamiya, Masahiro Goto
Pollinosis, a typical seasonal allergy, is a serious public health problem. Limited numbers of patients receive curative immunotherapy instead of symptomatic therapy; however, there are still some concerns about the inconvenience and side effects of subcutaneous injections and sublingual administration caused by immunotherapy. Here, we propose a simple and safe transcutaneous immunotherapy using solid-in-oil (S/O) nanodispersions loaded with vaccine T cell epitope peptides derived from pollen allergen. S/O nanodispersions are oil-based dispersions of antigens coated with hydrophobic surfactants...
July 10, 2017: International Journal of Pharmaceutics
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