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https://www.readbyqxmd.com/read/28819261/modified-vaccinia-virus-ankara-preferentially-targets-antigen-presenting-cells-in-vitro-ex-vivo-and-in-vivo
#1
Arwen F Altenburg, Carolien E van de Sandt, Bobby W S Li, Ronan J MacLoughlin, Ron A M Fouchier, Geert van Amerongen, Asisa Volz, Rudi W Hendriks, Rik L de Swart, Gerd Sutter, Guus F Rimmelzwaan, Rory D de Vries
Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818566/a-synthetic-human-cytomegalovirus-pp65-ie1-fusion-antigen-efficiently-induces-and-expands-virus-specific-t-cells
#2
Ellen K Link, Christine Brandmüller, Yasemin Suezer, Stefanie Ameres, Asisa Volz, Andreas Moosmann, Gerd Sutter, Michael H Lehmann
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28815417/cellular-interactome-analysis-of-vaccinia-virus-k7-protein-identifies-three-transport-machineries-as-binding-partners-for-k7
#3
Ye Li, Youyang Ke, Leiliang Zhang
Identification of viral-host interacting proteins will contribute to understanding of how poxvirus exploits the host cellular machinery. The vaccinia virus gene K7R encodes a conserved protein K7 in most orthopoxviruses. To gain insight into the biology of K7, we investigated the cellular interactome of K7 by GST pulldown coupled with mass spectrometry. The top categories of identified proteins contained components of trafficking machineries. We selected key components of three transport machineries including coatomer, retromer, and CHEVI to further confirm their binding abilities to K7...
August 16, 2017: Virus Genes
https://www.readbyqxmd.com/read/28813507/comparison-of-homologous-and-heterologous-prime-boost-vaccine-approaches-using-modified-vaccinia-ankara-and-soluble-protein-to-induce-neutralizing-antibodies-by-the-human-cytomegalovirus-pentamer-complex-in-mice
#4
Flavia Chiuppesi, Felix Wussow, Louise Scharf, Heidi Contreras, Han Gao, Zhuo Meng, Jenny Nguyen, Peter A Barry, Pamela J Bjorkman, Don J Diamond
Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC...
2017: PloS One
https://www.readbyqxmd.com/read/28808676/efficacy-and-safety-of-doubly-regulated-vaccinia-virus-in-a-mouse-xenograft-model-of-multiple-myeloma
#5
Muneyoshi Futami, Kota Sato, Kanji Miyazaki, Kenshi Suzuki, Takafumi Nakamura, Arinobu Tojo
Multiple myeloma is a malignancy of plasma cells of the bone marrow. Although the prognosis is variable, no curative therapy has been defined. Vaccinia virus infects cancer cells and kills such cells in a variety of ways. These include direct infection, triggering of immunomediated cell death, and vascular collapse. The potential of the vaccinia virus as an anti-tumor therapy has attracted the attention of oncologists. Interestingly, our preliminary experiments revealed that myeloma cells were particularly susceptible to vaccinia virus...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28803862/recombinant-lcmv-vectors-induce-protective-immunity-following-homologous-and-heterologous-vaccinations
#6
Jessica Wingerath, Dmitrij Ostroumov, Norman Woller, Michael P Manns, Daniel D Pinschewer, Klaus Orlinger, Ursula Berka, Florian Kühnel, Thomas C Wirth
Successful vaccination against cancer and infectious diseases relies on the induction of adaptive immune responses that induce high-titer antibodies or potent cytoxic T cell responses. In contrast to humoral vaccines, the amplification of cellular immune responses is often hampered by anti-vector immunity that either pre-exists or develops after repeated homologous vaccination. Replication-defective lymphocytic choriomeningitis virus (LCMV) vectors represent a novel generation of vaccination vectors that induce potent immune responses while escaping recognition by neutralizing antibodies...
July 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28798405/progress-in-genome-wide-association-studies-of-schizophrenia-in-han-chinese-populations
#7
REVIEW
Weihua Yue, Xin Yu, Dai Zhang
Since 2006, genome-wide association studies of schizophrenia have led to the identification of numerous novel risk loci for this disease. However, there remains a geographical imbalance in genome-wide association studies, which to date have primarily focused on Western populations. During the last 6 years, genome-wide association studies in Han Chinese populations have identified both the sharing of susceptible loci across ethnicities and genes unique to Han Chinese populations. Here, we review recent progress in genome-wide association studies of schizophrenia in Han Chinese populations...
August 10, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28796556/systemic-virotherapy-for-multiple-myeloma
#8
Stefania Oliva, Manuela Gambella, Mario Boccadoro, Sara Bringhen
The multiple myeloma (MM) treatment scenario has changed considerably over the past few years. Several novel targeted therapies are currently under consideration including oncolytic virotherapy. Areas covered: This review provides an analysis of the mechanisms of action of virotherapy, and summarizes the preclinical and clinical studies of systemic virotherapy developed for the treatment of MM. Different types of viruses have been identified, including: adenovirus, vaccinia virus, herpes simplex virus 1, myxoma virus, reovirus, measles virus, vesicular stomatitis virus and coxsackievirus A21...
August 10, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28792942/hiv-1-neutralizing-antibody-induced-by-simian-adenovirus-and-poxvirus-mva-vectored-bg505-native-like-envelope-trimers
#9
Silvia Capucci, Edmund G Wee, Torben Schiffner, Celia C LaBranche, Nicola Borthwick, Albert Cupo, Jonathan Dodd, Hansi Dean, Quentin Sattentau, David Montefiori, Per J Klasse, Rogier W Sanders, John P Moore, Tomáš Hanke
Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1...
2017: PloS One
https://www.readbyqxmd.com/read/28790404/structural-characterization-of-human-vaccinia-related-kinases-vrk-bound-to-small-molecule-inhibitors-identifies-different-p-loop-conformations
#10
Rafael M Couñago, Charles K Allerston, Pavel Savitsky, Hatylas Azevedo, Paulo H Godoi, Carrow I Wells, Alessandra Mascarello, Fernando H de Souza Gama, Katlin B Massirer, William J Zuercher, Cristiano R W Guimarães, Opher Gileadi
The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771513/a-modified-vaccinia-ankara-vaccine-vector-expressing-a-mosaic-h5-hemagglutinin-reduces-viral-shedding-in-rhesus-macaques
#11
Nicholas W Florek, Attapon Kamlangdee, James P Mutschler, Brock Kingstad-Bakke, Nancy Schultz-Darken, Karl W Broman, Jorge E Osorio, Thomas C Friedrich
The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus...
2017: PloS One
https://www.readbyqxmd.com/read/28768725/immune-protection-by-a-cytomegalovirus-vaccine-vector-expressing-a-single-low-avidity-epitope
#12
Lisa Borkner, Katarzyna M Sitnik, Iryna Dekhtiarenko, Ann-Kathrin Pulm, Ronny Tao, Ingo Drexler, Luka Cicin-Sain
Experimental CMV-based vaccine vectors expressing a single MHC class I-restricted high-avidity epitope provided strong, T cell-dependent protection against viruses or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show that a mouse CMV (MCMV) vector provides complete immune control of recombinant vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the immediate-early MCMV gene ie2 The same epitope expressed within the early M45 gene provided no protection, although MCMV vectors expressing the high-avidity epitope SSIEFARL induced protective immunity irrespective of gene expression context...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28763795/intratumoral-delivery-of-inactivated-modified-vaccinia-virus-ankara-imva-induces-systemic-antitumor-immunity-via-sting-and-batf3-dependent-dendritic-cells
#13
Peihong Dai, Weiyi Wang, Ning Yang, Cristian Serna-Tamayo, Jacob M Ricca, Dmitriy Zamarin, Stewart Shuman, Taha Merghoub, Jedd D Wolchok, Liang Deng
Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show that infection of conventional dendritic cells (DCs) with heat- or ultraviolet-inactivated MVA leads to higher levels of interferon induction than MVA alone through the cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase)-STING cytosolic DNA-sensing pathway...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763302/intramuscularly-injected-neurotropin-reduced-muscular-mechanical-hyperalgesia-induced-by-repeated-cold-stress-in-rats
#14
Teruaki Nasu, Shiori Murase, Yoshiko Takeda-Uchimura, Kazue Mizumura
An extract of rabbit skin inflamed by inoculation with the vaccinia virus, neurotropin [by intravenous, oral, and intramuscular (i.m.) administration], has been used in China and Japan for the treatment of chronic pain. In this study, we investigated the analgesic mechanism of i.m. neurotropin. Rats were exposed to repeated cold stress, and muscular mechanical hyperalgesia was evaluated by measuring the withdrawal threshold of the gastrocnemius muscle using Randall-Selitto apparatus. I.m. but not subcutaneous, neurotropin dose dependently reduced the repeated cold stress-induced muscular mechanical hyperalgesia for 3 h, but it had no effect in normal rats...
July 31, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28762495/preparation-of-cell-cultures-and-vaccinia-virus-stocks
#15
Catherine A Cotter, Patricia L Earl, Linda S Wyatt, Bernard Moss
The culturing of cell lines used with vaccinia virus, both as monolayer and in suspension, is described. The preparation of chick embryo fibroblasts (CEF) is presented for use in the production of the highly attenuated and host range-restricted modified vaccinia virus Ankara (MVA) strain of vaccinia virus. Protocols for the preparation, titration, and trypsinization of vaccinia virus stocks, as well as viral DNA preparation and virus purification methods are also included. © 2017 by John Wiley & Sons, Inc.
August 1, 2017: Current Protocols in Protein Science
https://www.readbyqxmd.com/read/28762491/generation-of-recombinant-vaccinia-viruses
#16
Linda S Wyatt, Patricia L Earl, Bernard Moss
This unit describes how to infect cells with vaccinia virus and then transfect them with a plasmid-transfer vector or PCR fragment to generate a recombinant virus. Selection and screening methods used to isolate recombinant viruses and a method for the amplification of recombinant viruses are described. Finally, a method for live immunostaining that has been used primarily for detection of recombinant modified vaccinia virus Ankara (MVA) is presented. © 2017 by John Wiley & Sons, Inc.
August 1, 2017: Current Protocols in Protein Science
https://www.readbyqxmd.com/read/28760882/modified-vaccinia-virus-ankara-vector-induces-specific-cellular-and-humoral-responses-in-the-female-reproductive-tract-the-main-hiv-portal-of-entry
#17
Romain Marlin, Marie-Thérèse Nugeyre, Nicolas Tchitchek, Matteo Parenti, Hakim Hocini, Fahd Benjelloun, Claude Cannou, Nathalie Dereuddre-Bosquet, Yves Levy, Françoise Barré-Sinoussi, Gabriella Scarlatti, Roger Le Grand, Elisabeth Menu
The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes)...
July 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28759036/deficiency-in-vhr-dusp3-a-suppressor-of-focal-adhesion-kinase-reveals-its-role-in-regulating-cell-adhesion-and-migration
#18
Y-R Chen, H-C Chou, C-H Yang, H-Y Chen, Y-W Liu, T-Y Lin, C-L Yeh, W-T Chao, H-H Tsou, H-C Chuang, T-H Tan
Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin...
July 31, 2017: Oncogene
https://www.readbyqxmd.com/read/28754374/oh1-from-orf-virus-a-new-tyrosine-phosphatase-that-displays-distinct-structural-features-and-triple-substrate-specificity
#19
Danilo Segovia, Ahmed Haouz, Darío Porley, Natalia Olivero, Mariano Martínez, Mahendra Mariadassou, Mabel Berois, Gwenaëlle André-Leroux, Andrea Villarino
Viral tyrosine phosphatases such as VH1 from Vaccinia and Variola virus are recognized as important effectors of host-pathogen interactions. While proteins sharing sequence to VH1 have been identified in other viruses, their structural and functional characterization is not known. In this work, we determined the crystal structure of the VH1 homologue in the Orf virus, herein named OH1. Similarly to Variola and Vaccinia VH1, the structure of OH1 shows a dimer with the typical dual specificity phosphatase fold...
July 25, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28747505/insufficient-innate-immunity-contributes-to-the-susceptibility-of-the-castaneous-mouse-to-orthopoxvirus-infection
#20
Patricia L Earl, Jeffrey L Americo, Bernard Moss
The castaneous (CAST) mouse, a wild-derived inbred strain, is highly susceptible to orthopoxvirus infection by intranasal and systemic routes. The 50% lethal intraperitoneal dose of vaccinia virus (VACV) was 3 PFU for CAST mice, whereas BALB/c mice survived 10(6) PFU. At all times and in all organs analyzed, virus titers were higher in CAST than in BALB/c mice. In individual CAST mice, luciferase-expressing VACV was seen to replicate rapidly leading to death, whereas virus levels increased for a few days and then declined in BALB/c mice...
July 26, 2017: Journal of Virology
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