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https://www.readbyqxmd.com/read/28326624/current-status-of-clinical-trials-assessing-oncolytic-virus-therapy-for-urological-cancers
#1
REVIEW
Satoru Taguchi, Hiroshi Fukuhara, Yukio Homma, Tomoki Todo
Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells, thus killing them without harming normal cells. Notably, T-VEC (talimogene laherparepvec, formerly called OncoVEX(GM)(-)(CSF) ), an oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in October 2015, and was subsequently approved in Europe and Australia in 2016. The efficacies of many types of oncolytic viruses against urological cancers have been investigated in preclinical studies during the past decade, and some have already been tested in clinical trials...
March 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28322923/microspheres-prime-rmva-boost-vaccination-enhances-humoral-and-cellular-immune-response-in-ifnar-mice-conferring-protection-against-serotypes-1-and-4-of-bluetongue-virus
#2
Alejandro Marín-López, Eva Calvo-Pinilla, Diego Barriales, Gema Lorenzo, Javier Benavente, Alejandro Brun, Jose Manuel Martínez-Costas, Javier Ortego
Bluetongue virus (BTV) is the causative agent of bluetongue disease (BT), which affects domestic and wild ruminants. At the present, 27 different serotypes have been documented. Vaccination has been demonstrated as one of the most effective methods to avoid viral dissemination. To overcome the drawbacks associated with the use of inactivated and attenuated vaccines we engineered a new recombinant BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 that were incorporated into avian reovirus muNS-Mi microspheres (MS-VP2/VP7/NS1) and recombinant modified vaccinia virus Ankara (rMVA)...
March 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28322708/detection-and-molecular-characterization-of-zoonotic-poxviruses-circulating-in-the-amazon-region-of-colombia-2014
#3
Jose A Usme-Ciro, Andrea Paredes, Diana M Walteros, Erica Natalia Tolosa-Pérez, Katherine Laiton-Donato, Maria Del Carmen Pinzón, Brett W Petersen, Nadia F Gallardo-Romero, Yu Li, Kimberly Wilkins, Whitni Davidson, Jinxin Gao, Nishi Patel, Yoshinori Nakazawa, Mary G Reynolds, P S Satheshkumar, Ginny L Emerson, Andrés Páez-Martínez
During 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the Amazon Region of western Colombia. Samples from 6 patients were analyzed by serologic and PCR testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. These findings highlight the need for increased poxvirus surveillance in Colombia.
April 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28320935/triad-of-human-cellular-proteins-irf2-fam111a-and-rfc3-restrict-replication-of-orthopoxvirus-spi-1-host-range-mutants
#4
Debasis Panda, Daniel J Fernandez, Madhu Lal, Eugen Buehler, Bernard Moss
Viruses and their hosts can reach balanced states of evolution ensuring mutual survival, which makes it difficult to appreciate the underlying dynamics. To uncover hidden interactions, virus mutants that have lost defense genes may be used. Deletion of the gene that encodes serine protease inhibitor 1 (SPI-1) of rabbitpox virus and vaccinia virus, two closely related orthopoxviruses, prevents their efficient replication in human cells, whereas certain other mammalian cells remain fully permissive. Our high-throughput genome-wide siRNA screen identified host factors that prevent reproduction and spread of the mutant viruses in human cells...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28317863/dynamic-monitoring-of-membrane-nanotubes-formation-induced-by-vaccinia-virus-on-a-high-throughput-microfluidic-chip
#5
Min Xiao, Na Xu, Cheng Wang, Dai-Wen Pang, Zhi-Ling Zhang
Membrane nanotubes (MNTs) are physical connections for intercellular communication and induced by various viruses. However, the formation of vaccinia virus (VACV)-induced MNTs has never been studied. In this report, VACV-induced MNTs formation process was monitored on a microfluidic chip equipped with a series of side chambers, which protected MNTs from fluidic shear stress. MNTs were formed between susceptible cells and be facilitated by VACV infection through three patterns. The formed MNTs varied with cell migration and virus concentration...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298290/a-prime-boost-pfcs14k-m-mva-spfcs-m-vaccination-protocol-generates-robust-cd8-t-cell-and-antibody-responses-to-plasmodium-falciparum-circumsporozoite-protein-and-protects-mice-against-malaria
#6
Aneesh Vijayan, Ernesto Mejías-Pérez, Diego A Espinosa, Suresh C Raman, Carlos Oscar S Sorzano, Fidel Zavala, Mariano Esteban
Vaccines against the pre-erythrocytic stages of malaria are appealing, since the parasite can be eliminated before disease onset and since they offer the unique possibility of targeting the parasite with both antibodies and T cells. Although the role CD8(+) T cells in pre-erythrocytic malaria stages is well documented, a highly effective T cell-inducing vaccine remains to be advanced. Here we report the development of a prime-boost immunization regimen with the Plasmodium falciparum circumsporozoite protein (PfCS) fused to the oligomer-forming vaccinia virus A27 protein and a modified vaccinia virus Ankara (MVA) vector expressing PfCS...
March 15, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28298069/expression-of-vrk1-and-the-downstream-gene-banf1-in-esophageal-cancer
#7
Jin Li, Tingting Wang, Lu Pei, Junpeng Jing, Wentan Hu, Tiange Sun, Hongchun Liu
Esophageal cancer is considered one of the most malignant tumors, being characterized by rapid progression and poor outcomes. China has the highest incidence of esophageal cancer in the world. Hence, it is necessary to clarify the mechanisms underlying esophageal cancer progression. In this study, we examined the expression of vaccinia-related kinase 1 (VRK1) and barrier to autointegration factor 1 (BANF1) in tumor tissues at the mRNA and protein levels via real-time PCR and immunohistochemical analyses. The mRNA and protein expression levels of VRK1 and BANF1 were higher in tumor tissues than in adjacent normal tissues...
March 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28291882/immune-responses-to-novel-adenovirus-type-26-and-modified-vaccinia-virus-ankara-vectored-ebola-vaccines-at-1-year
#8
Rebecca L Winslow, Iain D Milligan, Merryn Voysey, Kerstin Luhn, Georgi Shukarev, Macaya Douoguih, Matthew D Snape
No abstract text is available yet for this article.
March 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28289079/deletion-of-f4l-ribonucleotide-reductase-in-vaccinia-virus-produces-a-selective-oncolytic-virus-and-promotes-anti-tumor-immunity-with-superior-safety-in-bladder-cancer-models
#9
Kyle G Potts, Chad R Irwin, Nicole A Favis, Desmond B Pink, Krista M Vincent, John D Lewis, Ronald B Moore, Mary M Hitt, David H Evans
Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high-grade disease, Bacillus Calmette-Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2). The F4L-deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor-selective replication and cell killing...
March 13, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28280747/rna-seq-based-transcriptome-analysis-of-the-type-i-interferon-host-response-upon-vaccinia-virus-infection-of-mouse-cells
#10
Bruno Hernáez, Graciela Alonso, Juan Manuel Alonso-Lobo, Alberto Rastrojo, Cornelius Fischer, Sascha Sauer, Begoña Aguado, Antonio Alcamí
Vaccinia virus (VACV) encodes the soluble type I interferon (IFN) binding protein B18 that is secreted from infected cells and also attaches to the cell surface, as an immunomodulatory strategy to inhibit the host IFN response. By using next generation sequencing technologies, we performed a detailed RNA-seq study to dissect at the transcriptional level the modulation of the IFN based host response by VACV and B18. Transcriptome profiling of L929 cells after incubation with purified recombinant B18 protein showed that attachment of B18 to the cell surface does not trigger cell signalling leading to transcriptional activation...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28275183/vaccinia-virus-a6-is-a-two-domain-protein-requiring-a-cognate-n-terminal-domain-for-full-viral-membrane-assembly-activity
#11
Xiangzhi Meng, Lloyd Rose, Yue Han, Junpeng Deng, Yan Xiang
Poxvirus virion biogenesis is a complex, multistep process, starting with the formation of crescent-shaped viral membranes, followed by their enclosure of viral core to form the spherical immature virions. Crescent formation requires a group of proteins that are highly conserved among poxviruses, including A6 and A11 of vaccinia virus (VACV). To gain a better understanding of the molecular function of A6, we established a HeLa cell line that inducibly expressed VACV-A6, which allowed us to construct VACV mutants with A6 deletion or mutation...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28271474/antibody-recognition-of-immunodominant-vaccinia-virus-envelope-proteins
#12
Dirk M Zajonc
Vaccinia Virus (VACV) is an enveloped double stranded DNA virus and the active ingredient of the smallpox vaccine. The systematic administration of this vaccine led to the eradication of circulating smallpox (variola virus, VARV) from the human population. As a tribute to its success, global immunization was ended in the late 1970s. The efficacy of the vaccine is attributed to a robust production of protective antibodies against several envelope proteins of VACV, which cross-protect against infection with pathogenic VARV...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28259752/co-administration-of-recombinant-major-envelope-proteins-ra27l-and-rh3l-of-buffalopox-virus-provides-enhanced-immunogenicity-and-protective-efficacy-in-animal-models
#13
Amit Kumar, Revanaiah Yogisharadhya, Gnanavel Venkatesan, Veerakyathappa Bhanuprakash, Awadh Bihari Pandey, Sathish Bhadravati Shivachandra
Buffalopox virus (BPXV) and other vaccinia-like viruses (VLVs) are causing an emerging/re-emerging zoonosis affecting buffaloes, cattle and humans in India and other countries. A27L and H3L are immuno-dominant major envelope proteins of intracellular mature virion (IMV) of orthopoxviruses (OPVs) and are highly conserved with an ability to elicit neutralizing antibodies. In the present study, two recombinant proteins namely; rA27L (21S to E110; ∼30 kDa) and rH3L(1M to I280; ∼50 kDa) of BPXV-Vij/96 produced from Escherichia coli were used in vaccine formulation...
March 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28257484/the-vaccinia-virus-k7-protein-promotes-histone-methylation-associated-with-heterochromatin-formation
#14
Wondimagegnehu M Teferi, Megan A Desaulniers, Ryan S Noyce, Mira Shenouda, Brittany Umer, David H Evans
It has been well established that many vaccinia virus proteins suppress host antiviral pathways by targeting the transcription of antiviral proteins, thus evading the host innate immune system. However, whether viral proteins have an effect on the host's overall cellular transcription is less understood. In this study we investigated the regulation of heterochromatin during vaccinia virus infection. Heterochromatin is a highly condensed form of chromatin that is less transcriptionally active and characterized by methylation of histone proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28256358/safety-and-immunogenicity-of-a-modified-vaccinia-ankara-vaccine-using-three-immunization-schedules-and-two-modes-of-delivery-a-randomized-clinical-non-inferiority-trial
#15
Lisa A Jackson, Sharon E Frey, Hana M El Sahly, Mark J Mulligan, Patricia L Winokur, Karen L Kotloff, James D Campbell, Robert L Atmar, Irene Graham, Evan J Anderson, Edwin L Anderson, Shital M Patel, Colin Fields, Wendy Keitel, Nadine Rouphael, Heather Hill, Johannes B Goll
INTRODUCTION: To guide the use of modified vaccinia Ankara (MVA) vaccine in response to a release of smallpox virus, the immunogenicity and safety of shorter vaccination intervals, and administration by jet injector (JI), were compared to the standard schedule of administration on Days 1 and 29 by syringe and needle (S&N). METHODS: Healthy adults 18-40years of age were randomly assigned to receive MVA vaccine subcutaneously by S&N on Days 1 and 29 (standard), Days 1 and 15, or Days 1 and 22, or to receive the vaccine subcutaneously by JI on Days 1 and 29...
February 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28246125/zmpste24-defends-against-influenza-and-other-pathogenic-viruses
#16
Bishi Fu, Lingyan Wang, Shitao Li, Martin E Dorf
Zinc metallopeptidase STE24 (ZMPSTE24) is a transmembrane metalloprotease whose catalytic activity is critical for processing lamin A on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum. We now report ZMPSTE24 is a virus-specific effector that restricts enveloped RNA and DNA viruses, including influenza A, Zika, Ebola, Sindbis, vesicular stomatitis, cowpox, and vaccinia, but not murine leukemia or adenovirus. ZMPSTE24-mediated antiviral action is independent of protease activity...
February 28, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28241999/safety-and-immunogenicity-of-mammalian-cell-derived-and-modified-vaccinia-ankara-vectored-african-swine-fever-subunit-antigens-in-swine
#17
Jaime Lopera-Madrid, Jorge E Osorio, Yongqun He, Zuoshuang Xiang, L Garry Adams, Richard C Laughlin, Waithaka Mwangi, Sandesh Subramanya, John Neilan, David Brake, Thomas G Burrage, William Clay Brown, Alfonso Clavijo, Mangkey A Bounpheng
A reverse vaccinology system, Vaxign, was used to identify and select a subset of five African Swine Fever (ASF) antigens that were successfully purified from human embryonic kidney 293 (HEK) cells and produced in Modified vaccinia virus Ankara (MVA) viral vectors. Three HEK-purified antigens [B646L (p72), E183L (p54), and O61R (p12)], and three MVA-vectored antigens [B646L, EP153R, and EP402R (CD2v)] were evaluated using a prime-boost immunization regimen swine safety and immunogenicity study. Antibody responses were detected in pigs following prime-boost immunization four weeks apart with the HEK-293-purified p72, p54, and p12 antigens...
March 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28219080/survival-of-tissue-resident-memory-t-cells-requires-exogenous-lipid-uptake-and-metabolism
#18
Youdong Pan, Tian Tian, Chang Ook Park, Serena Y Lofftus, Shenglin Mei, Xing Liu, Chi Luo, John T O'Malley, Ahmed Gehad, Jessica E Teague, Sherrie J Divito, Robert Fuhlbrigge, Pere Puigserver, James G Krueger, Gökhan S Hotamisligil, Rachael A Clark, Thomas S Kupper
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8(+) TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes...
February 20, 2017: Nature
https://www.readbyqxmd.com/read/28218453/divergent-roles-of-%C3%AE-and-%C3%AE-actin-isoforms-during-spread-of-vaccinia-virus
#19
N Bishara Marzook, Sharissa L Latham, Helena Lynn, Christopher Mckenzie, Christine Chaponnier, Georges E Grau, Timothy P Newsome
Actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N-terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. Here we show that virus-tipped actin comets are composed of β- and γ-actin. We employed isoform-specific siRNA knockdown to examine the role of the two isoforms in VACV-induced actin comets...
February 20, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28211116/ac-dielectrophoretic-manipulation-and-electroporation-of-vaccinia-virus-using-carbon-nanoelectrode-arrays
#20
Foram Ranjeet Madiyar, Sherry Basset, Omer Farooq, Stefan Rothenburg, Christopher Culbertson, Jun Li
This paper reports the capture and detection of vaccinia virus particles based on AC dielectrophoresis (DEP) and electrochemical impedance measurements employing an embedded vertically aligned carbon nanofiber (VACNF) nanoelectrode array (NEA) versus a macroscopic indium-tin-oxide (ITO) transparent electrode in a "points-and-lid" configuration. The nano-DEP device was fabricated by bonding two SU-8 covered electrodes patterned using photolithography. The bottom electrode contains a 200 × 200 μm(2) active region on a randomly distributed NEA and the top electrode contains a microfluidic channel in SU-8 spin-coated on ITO to guide the flow of the virus solution...
February 17, 2017: Electrophoresis
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