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https://www.readbyqxmd.com/read/28453967/therapeutic-vaccination-for-chronic-hepatitis-b
#1
REVIEW
Anna D Kosinska, Tanja Bauer, Ulrike Protzer
A therapeutic vaccine is meant to activate the patient's immune system to fight and finally control or ideally eliminate an already established infectious pathogen. Whereas the success of prophylactic vaccination is based on rapid antibody-mediated neutralization of an invading pathogen, control and elimination of persistent viruses such as hepatitis, herpes or papilloma viruses requires multi-specific and polyfunctional effector T cell responses. These are ideally directed against continuously expressed viral antigens to keep the pathogen in check...
April 25, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28448566/il-33-st2-pathway-drives-regulatory-t-cell-dependent-suppression-of-liver-damage-upon-cytomegalovirus-infection
#2
Branka Popovic, Mijo Golemac, Jürgen Podlech, Jelena Zeleznjak, Lidija Bilic-Zulle, Miodrag L Lukic, Luka Cicin-Sain, Matthias J Reddehase, Tim Sparwasser, Astrid Krmpotic, Stipan Jonjic
Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection...
April 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28446752/near-atomic-structure-of-japanese-encephalitis-virus-reveals-critical-determinants-of-virulence-and-stability
#3
Xiangxi Wang, Shi-Hua Li, Ling Zhu, Qing-Gong Nian, Shuai Yuan, Qiang Gao, Zhongyu Hu, Qing Ye, Xiao-Feng Li, Dong-Yang Xie, Neil Shaw, Junzhi Wang, Thomas S Walter, Juha T Huiskonen, Elizabeth E Fry, Cheng-Feng Qin, David I Stuart, Zihe Rao
Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual "hole" on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice...
April 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28446674/broadening-cd4-and-cd8-t-cell-responses-against-hepatitis-c-virus-by-vaccination-with-ns3-overlapping-peptide-panels-in-cross-priming-liposomes
#4
Jonathan Filskov, Marianne Mikkelsen, Paul R Hansen, Jan P Christensen, Allan R Thomsen, Peter Andersen, Jens Bukh, Else Marie Agger
Despite the introduction of effective drugs to treat patients with chronic hepatitis C virus (HCV) infection, a vaccine would be the only means to substantially reduce the worldwide disease burden. An incomplete understanding of how HCV interacts with its human host and evades immune surveillance has hampered vaccine development. It is generally accepted that in infected individuals, a narrow repertoire of exhausted T cells is a hallmark of persistent infection, whereas broad vigorous CD4(+) and CD8(+) T cell responses are associated with control of acute hepatitis C...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446665/dense-array-of-spikes-on-hiv-1-virion-particles
#5
Armando Stano, Daniel P Leaman, Arthur S Kim, Lei Zhang, Ludovic Autin, Jidnyasa Ingale, Syna K Gift, Jared Truong, Richard T Wyatt, Arthur J Olson, Michael B Zwick
HIV-1 is rare among viruses for having a low number of envelope glycoprotein (Env) spikes per virion, i.e. ∼7-14. This exceptional feature has been associated with avoidance of humoral immunity, i.e. B cell activation and antibody neutralization. Virus-like particles (VLPs) with increased density of Env are being pursued for vaccine development; however these typically require protein engineering that alters Env structure. Here, we used instead a strategy that targets the producer cell. We employed fluorescence activated cell sorting (FACS) to sort for cells that are recognized by trimer crossreactive broadly neutralizing antibody (bnAb) and not by non-neutralizing antibodies...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446441/long-term-persistence-of-cell-mediated-and-humoral-responses-to-a-h1n1-pdm09-influenza-virus-vaccines-and-the-role-of-the-as03-adjuvant-system-in-adults-during-two-randomized-controlled-trials
#6
Robbert G van der Most, Frédéric Clément, Julie Willekens, Walthère Dewé, Karl Walravens, David W Vaughn, Geert Leroux-Roels
We investigated the role of AS03, an α-tocopherol oil-in-water-emulsion-based Adjuvant System, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm09 influenza vaccines. In two studies (NCT00968539/NCT00989287), a total of 261 healthy adults (age ≤60 years) were randomized to receive two doses of AS03-adjuvanted vaccine containing 3.75 μg hemagglutinin, or non-adjuvanted vaccine containing 15 μg hemagglutinin (in Study A) or 3.75 μg hemagglutinin (in Study B), 21 days apart...
April 26, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28446240/molecular-mechanisms-by-which-herv-k-gag-interferes-with-hiv-1-gag-assembly-and-particle-infectivity
#7
Kazuaki Monde, Hiromi Terasawa, Yusuke Nakano, Ferri Soheilian, Kunio Nagashima, Yosuke Maeda, Akira Ono
BACKGROUND: Human endogenous retroviruses (HERVs), the remnants of ancient retroviral infections, constitute approximately 8% of human genomic DNA. Since HERV-K Gag expression is induced by HIV-1 Tat in T cells, induced HERV-K proteins could affect HIV-1 replication. Indeed, previously we showed that HERV-K Gag and HIV-1 Gag coassemble and that this appears to correlate with the effect of HERV-K Gag expression on HIV-1 particle release and its infectivity. We further showed that coassembly requires both MA and NC domains, which presumably serve as scaffolding for Gag via their abilities to bind membrane and RNA, respectively...
April 26, 2017: Retrovirology
https://www.readbyqxmd.com/read/28446055/investigational-drugs-for-nasopharyngeal-carcinoma
#8
Brigette B Y Ma, Edwin P Hui, Anthony T C Chan
Nasopharyngeal carcinoma (NPC) is endemic to Southern China and Asia and is etiologically associated with the Epstein Barr virus (EBV). Whole exome and genome sequencing (WES, WGS) studies of NPC have reported several actionable therapeutic targets, and that the mutational load of NPC maybe comparable to that of squamous head and neck cancer. These unique biological characteristics have been exploited as potential targets and a wide range of investigational drugs are being investigated in clinical trials. Area covered: This review focused on the latest clinical development of the most promising classes of investigational agents in the treatment of advanced NPC...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28445479/in-vitro-and-in-vivo-antivirus-activity-of-an-anti-programmed-death-ligand-1-pd-l1-rat-bovine-chimeric-antibody-against-bovine-leukemia-virus-infection
#9
Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Yamato Sajiki, Yasuhiko Suzuki, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow...
2017: PloS One
https://www.readbyqxmd.com/read/28443094/serum-igg-antibodies-from-pregnant-women-reacting-to-mimotopes-of-simian-virus-40-large-t-antigen-the-viral-oncoprotein
#10
Elisa Mazzoni, Mariantonietta Di Stefano, Josè R Fiore, Federica Destro, Marco Manfrini, John Charles Rotondo, Maria V Casali, Fortunato Vesce, Pantaleo Greco, Gennaro Scutiero, Fernanda Martini, Mauro G Tognon
Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28440692/both-hepatitis-c-virus-specific-t-cell-responses-and-il28b-rs12979860-single-nucleotide-polymorphism-genotype-influence-antihepatitis-c-virus-treatment-outcome-in-patients-with-chronic-hepatitis-c
#11
José M Benito, Javier García-Samaniego, Marcial García, Antonio Madejón, Luz Martín-Carbonero, Alfonso Cabello, Beatriz Álvarez, Miguel Górgolas, Norma Rallón
Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy...
April 25, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28439065/multidisciplinary-study-of-the-secondary-immune-response-in-grandparents-re-exposed-to-chickenpox
#12
B Ogunjimi, J Van den Bergh, P Meysman, S Heynderickx, K Bergs, H Jansen, E Leuridan, A Vorsters, H Goossens, K Laukens, N Cools, Viggo Van Tendeloo, N Hens, P Van Damme, Evelien Smits, Ph Beutels
Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#13
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28434944/dose-dependent-t-cell-dynamics-and-cytokine-cascade-following-rvsv-zebov-immunization
#14
Christine Dahlke, Rahel Kasonta, Sebastian Lunemann, Verena Krähling, Madeleine E Zinser, Nadine Biedenkopf, Sarah K Fehling, My L Ly, Anne Rechtien, Hans C Stubbe, Flaminia Olearo, Saskia Borregaard, Alen Jambrecina, Felix Stahl, Thomas Strecker, Markus Eickmann, Marc Lütgehetmann, Michael Spohn, Stefan Schmiedel, Ansgar W Lohse, Stephan Becker, Marylyn M Addo
BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date...
April 5, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28433716/development-of-a-monoclonal-antibody-against-the-cd3%C3%AE%C2%B5-of-olive-flounder-paralichthys-olivaceus-and-its-application-in-evaluating-immune-response-related-to-cd3%C3%AE%C2%B5
#15
Jae Wook Jung, Jung Seok Lee, Young Rim Kim, Se Pyeong Im, Si Won Kim, Jassy Mary S Lazarte, Jaesung Kim, Kim D Thompson, Jong Pyo Suh, Tae Sung Jung
The T cell receptor (TCR) is the binding site of antigen and is responsible for specifically activating the adaptive immune response. CD3, an essential component of the CD3-TCR complex, is known to be composed of γδ and ε chains in teleost. However, there are few monoclonal antibodies (mAb) available to identify these molecules on T cells, so we aimed to produce a mAb against CD3ε to improve our understanding of T cell immune response in olive flounder (Paralichthys olivaceus). CD3ε recombinant protein was expressed in yeast, the expression of which was confirmed by SDS-PAGE, MALDI-TOF/TOF MS and Western blot analysis...
April 20, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28433429/immunological-function-of-langerhans-cells-in-hiv-infection
#16
Takamitsu Matsuzawa, Youichi Ogawa, Kohji Moriishi, Shinji Shimada, Tatsuyoshi Kawamura
BACKGROUND: Langerhans cells (LCs) are one of the initial target cells for HIV following sexual exposure and they are productively infected by HIV. HIV-infected LCs migrate to the draining lymph nodes (dLNs) and transmit the virus to CD4(+) T cells, leading to the dissemination of HIV. In contrast with the role of LCs in initial HIV acquisition, little is known about the modulation of immune responses by HIV-infected LCs. OBJECTIVE: We aimed to elucidate the induction of HIV-specific CD8(+) T cells and regulatory T cells (Tregs), both of which play important roles in regulating the progression of HIV infection...
April 9, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28430779/a-coevolution-analysis-for-identifying-protein-protein-interactions-by-fourier-transform
#17
Changchuan Yin, Stephen S-T Yau
Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28429853/molecular-cloning-of-mda5-phylogenetic-analysis-of-rig-i-like-receptors-rlrs-and-differential-gene-expression-of-rlrs-interferons-and-proinflammatory-cytokines-after-in%C3%A2-vitro-challenge-with-ipnv-isav-and-sav-in-the-salmonid-cell-line-to
#18
I-K G Nerbøvik, M A Solheim, H Ø Eggestøl, A Rønneseth, R A Jakobsen, H I Wergeland, G T Haugland
The RIG-I receptors RIG-I, MDA5 and LGP2 are involved in viral recognition, and they have different ligand specificity and recognize different viruses. Activation of RIG-I-like receptors (RLRs) leads to production of cytokines essential for antiviral immunity. In fish, most research has focused on interferons, and less is known about the production of proinflammatory cytokines during viral infections. In this study, we have cloned the full-length MDA5 sequence in Atlantic salmon, and compared it with RIG-I and LGP2...
April 21, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28428612/granzyme-k-deficient-mice-show-no-evidence-of-impaired-anti-viral-immunity
#19
Lars T Joeckel, Cody C Allison, Mark Pellegrini, Catherina H Bird, Phillip Ian Bird
The biological role of granzyme K, a serine protease of cytotoxic T lymphocytes (CTL), is controversial. It has been reported to induce perforin-mediated cell death in vitro, but is also reported to be non-cytotoxic and to operate in inflammatory processes. To elucidate the biological role of this protease we have deleted the granzyme K gene in mice (mutant allele: Gzmk(tm1.1Pib); MGI:5636646). Gzmk(-/-) mice are healthy, anatomically normal, fecund, and show normal hematopoietic development. Gzmk(-/-) mice readily recover from Lymphocytic choriomeningitis virus and mouse pox Ectromelia virus infection...
April 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28428537/human-cytomegalovirus-induces-cellular-and-humoral-virus-specific-immune-responses-in-humanized-blt-mice
#20
Lindsey B Crawford, Rebecca Tempel, Daniel N Streblow, Craig Kreklywich, Patricia Smith, Louis J Picker, Jay A Nelson, Patrizia Caposio
The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice...
April 20, 2017: Scientific Reports
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