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https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#1
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28728855/tissue-plasminogen-activator-tpa-signal-sequence-enhances-immunogenicity-of-mva-based-vaccine-against-tuberculosis
#2
Yiming Kou, Yongqing Xu, Zhilei Zhao, Jie Liu, Yang Wu, Qingrui You, Linli Wang, Feng Gao, Linjun Cai, Chunlai Jiang
Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28727817/immunogenicity-of-a-novel-clade-b-hiv-1-vaccine-combination-results-of-phase-1-randomized-placebo-controlled-trial-of-an-hiv-1-gm-csf-expressing-dna-prime-with-a-modified-vaccinia-ankara-vaccine-boost-in-healthy-hiv-1-uninfected-adults
#3
Susan P Buchbinder, Nicole A Grunenberg, Brittany J Sanchez, Kelly E Seaton, Guido Ferrari, M Anthony Moody, Nicole Frahm, David C Montefiori, Christine M Hay, Paul A Goepfert, Lindsey R Baden, Harriet L Robinson, Xuesong Yu, Peter B Gilbert, M Juliana McElrath, Yunda Huang, Georgia D Tomaras
BACKGROUND: A phase 1 trial of a clade B HIV vaccine in HIV-uninfected adults evaluated the safety and immunogenicity of a DNA prime co-expressing GM-CSF (Dg) followed by different numbers and intervals of modified vaccinia Ankara Boosts (M). Both vaccines produce virus-like particles presenting membrane-bound Env. METHODS: Four US sites randomized 48 participants to receiving 1/10th the DNA dose as DgDgMMM given at 0, 2, 4, 6 and 8 months, or full dose DgDgM_M or DgDgMM_M regimens, given at 0, 2, 4, and 8 months, and 0, 2, 4, 6, and 10 months, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28727764/vaccinia-virus-and-cowpox-virus-are-not-susceptible-to-the-interferon-induced-antiviral-protein-mxa
#4
María M Lorenzo, Juana M Sanchez-Puig, Rafael Blasco
MxA protein is expressed in response to type I and type III Interferon and constitute an important antiviral factor with broad antiviral activity to diverse RNA viruses. In addition, some studies expand the range of MxA antiviral activity to include particular DNA viruses like Monkeypox virus (MPXV) and African Swine Fever virus (ASFV). However, a broad profile of activity of MxA to large DNA viruses has not been established to date. Here, we investigated if some well characterized DNA viruses belonging to the Poxviridae family are sensitive to human MxA...
2017: PloS One
https://www.readbyqxmd.com/read/28724763/species-specificity-of-vaccinia-virus-complement-control-protein-towards-bovine-classical-pathway-is-governed-primarily-by-direct-interaction-of-its-acidic-residues-with-factor-i
#5
Jitendra Kumar, Viveka Nand Yadav, Swastik Phulera, Ashish Kamble, Avneesh Kumar Gautam, Hemendra Singh Panwar, Arvind Sahu
Poxviruses display species tropism - variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. Consistent with this, variola virus complement regulator SPICE exhibit selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator VCP display selectivity in inhibiting the bovine alternative complement pathway. In the present study, we examined the species-specificity of VCP and SPICE towards the classical pathway (CP). We observed that VCP is ∼43-fold superior in inhibiting bovine CP than SPICE...
July 19, 2017: Journal of Virology
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
#6
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/28720468/production-of-a-chikungunya-vaccine-using-a-cho-cell-and-attenuated-viral-based-platform-technology
#7
Preethi Eldi, Tamara H Cooper, Liang Liu, Natalie A Prow, Kerrilyn R Diener, Paul M Howley, Andreas Suhrbier, John D Hayball
Vaccinia-based systems have been extensively explored for the development of recombinant vaccines. Herein we describe an innovative vaccinia virus (VACV)-derived vaccine platform technology termed Sementis Copenhagen Vector (SCV), which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene D13L. A SCV cell substrate line was developed for SCV vaccine production by engineering CHO cells to express D13 and the VACV host-range factor CP77, because CHO cells are routinely used for manufacture of biologics...
July 15, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28701395/preferential-targeting-of-conserved-gag-regions-after-vaccination-with-a-heterologous-dna-prime-modified-vaccinia-ankara-mva-boost-hiv-1-vaccine-regimen
#8
Asli Bauer, Lilli Podola, Philipp Mann, Marco Missanga, Antelmo Haule, Lwitiho Sudi, Charlotta Nilsson, Bahati Kaluwa, Cornelia Lueer, Maria Mwakatima, Patricia J Munseri, Leonard Maboko, Merlin L Robb, Sodsai Tovanabutra, Gustavo Kijak, Mary Marovich, Sheena McCormack, Sarah Joseph, Eligius Lyamuya, Britta Wahren, Eric Sandström, Gunnel Biberfeld, Michael Hoelscher, Muhammad Bakari, Arne Kroidl, Christof Geldmacher
Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28701329/multisubunit-dna-dependent-rna-polymerases-from-vaccinia-virus-and-other-nucleocytoplasmic-large-dna-viruses-impressions-from-the-age-of-structure
#9
REVIEW
Yeva Mirzakhanyan, Paul D Gershon
The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus...
September 2017: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/28685222/characterization-of-eptesipoxvirus-a-novel-poxvirus-from-a-microchiropteran-bat
#10
Shin-Lin Tu, Yoshinori Nakazawa, Jinxin Gao, Kimberly Wilkins, Nadia Gallardo-Romero, Yu Li, Ginny L Emerson, Darin S Carroll, Chris Upton
The genome of Eptesipoxvirus (EPTV) is the first poxvirus genome isolated from a microbat. The 176,688 nt sequence, which is believed to encompass the complete coding region of the virus, is 67% A+T and is predicted to encode 191 genes. 11 of these genes have no counterpart in GenBank and are therefore unique to EPTV. The presence of a distantly related ortholog of Vaccinia virus F5L in EPTV uncovered a link with fragmented F5L orthologs in Molluscum contagiosum virus/squirrelpox and clade II viruses. Consistent with the unique position of EPTV approximately mid-point between the orthopoxviruses and the clade II viruses, EPTV has 11 genes that are specific to the orthopoxviruses and 13 genes that are typical, if not exclusive, to the clade II poxviruses...
July 6, 2017: Virus Genes
https://www.readbyqxmd.com/read/28679776/phase-i-trial-of-intravenous-oncolytic-vaccinia-virus-gl-onc1-with-cisplatin-and-radiotherapy-in-patients-with-locoregionally-advanced-head-and-neck-carcinoma
#11
Loren K Mell, Kevin T Brumund, Gregory A Daniels, Sunil J Advani, Kaveh Zakeri, Mary E Wright, Sara-Jane Onyeama, Robert A Weisman, Parag R Sanghvi, Peter J Martin, Aladar A Szalay
Pre-clinical models have shown that the effectiveness of GL-ONC1, a modified <p>oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study</p> <p>was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy</p> <p>to patients with primary, non-metastatic head and neck cancer.</p> <p>EXPERIMENTAL DESIGN: Patients with locoregionally advanced unresected, non-metastatic</p> <p>carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were</p> <p>treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and</p> <p>chemotherapy...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28676302/comparison-of-three-dimensional-synergistic-analyses-of-percentage-versus-logarithmic-data-in-antiviral-studies
#12
Donald F Smee, Mark N Prichard
Cell culture antiviral experiments were conducted in order to understand the relationship between percentage data generated by plaque reduction (PR) and logarithmic data derived by virus yield reduction (VYR) assays, using three-dimensional MacSynergy II software. The relationship between percentage and logarithmic data has not been investigated previously. Interpretation of drug-drug interactions is based on a Volume of Synergy (VS) calculation, which can be positive (synergy), negative (antagonistic), or neutral (no or minimal interaction)...
July 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28666733/virtual-screening-synthesis-and-biological-evaluation-of-dna-intercalating-antiviral-agents
#13
Kyrylo Klimenko, Sergey Lyakhov, Marina Shibinskaya, Alexander Karpenko, Gilles Marcou, Dragos Horvath, Marina Zenkova, Elena Goncharova, Rinat Amirkhanov, Andrei Krysko, Sergei Andronati, Igor Levandovskiy, Pavel Polishchuk, Victor Kuz'min, Alexandre Varnek
This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators. This resulted in 12 hits which then were synthesized and tested for antiviral activity against VaV together with 43 compounds earlier studied against VSV...
June 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28665497/protein-and-modified-vaccinia-virus-ankara-based-influenza-virus-nucleoprotein-vaccines-are-differentially-immunogenic-in-balb-c-mice
#14
Arwen F Altenburg, Sofia E Magnusson, Fons Bosman, Linda Stertman, Rory D de Vries, Guus F Rimmelzwaan
Because of the high variability of seasonal influenza viruses and the eminent threat of influenza viruses with pandemic potential, there is great interest in the development of vaccines that induce broadly protective immunity. Most likely, broadly protective influenza vaccines are based on conserved proteins, such as nucleoprotein (NP). NP is a vaccine target of interest since it has been shown to induce cross-reactive antibody and T cell responses. Here we tested and compared various NP-based vaccine preparations for their capacity to induce humoral and cellular immune responses to influenza virus NP...
June 30, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28659488/inhibition-of-poxvirus-gene-expression-and-genome-replication-by-bisbenzimide-derivatives
#15
Artur Yakimovich, Moona Huttunen, Benno Zehnder, Lesley J Coulter, Victoria Gould, Christoph Schneider, Manfred Kopf, Colin J McInnes, Urs F Greber, Jason Mercer
Virus infection of humans and livestock can be devastating for individuals and populations, sometimes resulting in large economic and societal impact. Prevention of virus disease by vaccination or anti-viral agents is difficult to achieve. A notable exception was the eradication of human smallpox by vaccination over 30 years ago. Today, humans and animals remain susceptible to poxvirus infections, including zoonotic poxvirus transmission. Here we identified a small molecule, bisbenzimide (bisbenzimidazole) and its derivatives, as potent agents against prototypic poxvirus infection in cell culture...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28659486/differential-innate-immune-signaling-in-macrophages-by-wild-type-vaccinia-mature-virus-and-a-mutant-virus-deleting-a26-protein
#16
Siti Khadijah Kasani, Huei-Yin Cheng, Kun-Hai Eason Yeh, Shu-Jung Chang, Paul Wei-Che Hsu, Shu-Yun Tung, Chung-Tiang Liang, Wen Chang
The Western Reserve (WR) strain of mature vaccinia virus contains an A26 envelope protein that mediates virus binding to cell surface laminin and subsequent endocytic entry into HeLa cells. Removal of A26 protein from mature virus generates a mutant WRΔA26 that enters HeLa cells through plasma membrane fusion. Here, we infected murine bone marrow-derived macrophages (BMDM) with wild-type WR and WRΔA26 and analyzed viral gene expression and cellular innate immune signaling. In contrast to previous studies in which HeLa cells infected by WR or WRΔA26 both expressed abundant viral late proteins, we found that WR expressed much less viral late protein than WRΔA26 in BMDM...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28651016/enhanced-light-microscopy-visualization-of-virus-particles-from-zika-virus-to-filamentous-ebolaviruses
#17
George G Daaboul, David S Freedman, Steven M Scherr, Erik Carter, Alexandru Rosca, David Bernstein, Chad E Mire, Krystle N Agans, Thomas Hoenen, Thomas W Geisbert, M Selim Ünlü, John H Connor
Light microscopy is a powerful tool in the detection and analysis of parasites, fungi, and prokaryotes, but has been challenging to use for the detection of individual virus particles. Unlabeled virus particles are too small to be visualized using standard visible light microscopy. Characterization of virus particles is typically performed using higher resolution approaches such as electron microscopy or atomic force microscopy. These approaches require purification of virions away from their normal millieu, requiring significant levels of expertise, and can only enumerate small numbers of particles per field of view...
2017: PloS One
https://www.readbyqxmd.com/read/28649801/vaccinia-virus-detection-in-dairy-products-made-with-milk-from-experimentally-infected-cows
#18
T M L de Oliveira, M I M C Guedes, I S Rehfeld, A C D Matos, A V Rivetti Júnior, A F da Cunha, M M O P Cerqueira, J S Abrahão, Z I P Lobato
Vaccinia virus (VACV) is the agent of bovine vaccinia (BV), an emerging zoonosis that causes exanthematic lesions on the teats of dairy cows and on the hands of milkers. The virus has been detected in the milk of naturally infected cows. The objective of this study was to investigate and quantify VACV DNA as well as the presence of infectious virus particles in samples of cheese curd, cheese whey and pasteurized milk produced using milk from cows experimentally inoculated with VACV-GP2, a Brazilian isolate of VACV (VACV-BR)...
June 26, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28637768/vrk2a-is-an-a-type-lamin-dependent-nuclear-envelope-kinase-that-phosphorylates-baf
#19
K C Birendra, Danielle G May, Benjamin V Benson, Dae In Kim, Winnie G Shivega, Manaal H Ali, Randolph S Faustino, Alexandre R Campos, Kyle J Roux
The nuclear envelope (NE) is critical for numerous fundamental cellular functions and mutations in several NE constituents can lead to a heterogeneous spectrum of diseases. We used proximity biotinylation to uncover new constituents of the inner nuclear membrane (INM) by comparative BioID analysis of lamin-A, Sun2 and a minimal INM-targeting motif. These studies identified vaccinia-related kinase-2 (VRK2) as a candidate constituent of the INM. We determined that the transmembrane VRK2A isoform is retained at the NE by association with A-type lamins...
June 21, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28637757/going-against-the-tide-selective-cellular-protein-synthesis-during-virally-induced-host-shutoff
#20
Shuai Cao, Pragyesh Dhungel, Zhilong Yang
Many viral infections cause host shutoff, a state in which host protein synthesis is globally inhibited. Emerging evidence from vaccinia and influenza A virus infections indicates that subsets of cellular proteins are resistant to host shutoff and continue to be synthesized. Remarkably, the proteins of oxidative phosphorylation, the cellular energy generating machinery, are selectively synthesized in both cases. Identifying mechanisms that drive selective protein synthesis should facilitate understanding both viral replication and fundamental cell biology...
June 21, 2017: Journal of Virology
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