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Modified vaccinia virus ankara

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https://www.readbyqxmd.com/read/29343579/identification-of-poxvirus-genome-uncoating-and-dna-replication-factors-with-mutually-redundant-roles
#1
Baoming Liu, Debasis Panda, Jorge D Mendez-Rios, Sundar Ganesan, Linda S Wyatt, Bernard Moss
Genome uncoating is essential for replication of most viruses. For poxviruses, the process is divided into two stages: removal of the envelope allowing early gene expression, and breaching of the core wall allowing DNA release, replication and late gene expression. Subsequent studies showed that the host proteasome and the viral D5 protein, which has an essential role in DNA replication, are required for vaccinia virus (VACV) genome uncoating. In a search for additional VACV uncoating proteins, we noted a report that described a defect in DNA replication and late expression when the gene encoding a 68 kDa ankyrin-repeat/F box protein (68k-ank), associated with the cellular SCF ubiquitin ligase complex, was deleted from the attenuated modified vaccinia virus Ankara (MVA)...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29341877/characterizing-the-effects-of-insertion-of-a-5-2%C3%A2-kb-region-of-a-vacv-genome-which-contains-known-immune-evasion-genes-on-mva-immunogenicity
#2
Melissa R Ryerson, Joanna L Shisler
Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that is a popular vaccine vector candidate against many different pathogens. Its replication-restricted nature makes it a safe vaccine. However, higher doses or multiple boosts of MVA are necessary to elicit an immune response similar to wild-type VACV. Multiple strategies have been used to create modified MVA viruses that remain safe, but have increased immunogenicity. For example, one common strategy is to delete MVA immunomodulatory proteins in hopes of increasing the host immune response...
January 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29339750/a-single-dose-of-modified-vaccinia-ankara-expressing-ebola-virus-like-particles-protects-nonhuman-primates-from-lethal-ebola-virus-challenge
#3
Arban Domi, Friederike Feldmann, Rahul Basu, Nathanael McCurley, Kyle Shifflett, Jackson Emanuel, Michael S Hellerstein, Farshad Guirakhoo, Chiara Orlandi, Robin Flinko, George K Lewis, Patrick W Hanley, Heinz Feldmann, Harriet L Robinson, Andrea Marzi
Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013-2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV)...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29300297/e3l-and-f1l-gene-functions-modulate-the-protective-capacity-of-modified-vaccinia-virus-ankara-immunization-in-murine-model-of-human-smallpox
#4
Asisa Volz, Sylvia Jany, Astrid Freudenstein, Markus Lantermann, Holger Ludwig, Gerd Sutter
The highly attenuated Modified Vaccinia virus Ankara (MVA) lacks most of the known vaccinia virus (VACV) virulence and immune evasion genes. Today MVA can serve as a safety-tested next-generation smallpox vaccine. Yet, we still need to learn about regulatory gene functions preserved in the MVA genome, such as the apoptosis inhibitor genes F1L and E3L. Here, we tested MVA vaccine preparations on the basis of the deletion mutant viruses MVA-ΔF1L and MVA-ΔE3L for efficacy against ectromelia virus (ECTV) challenge infections in mice...
January 4, 2018: Viruses
https://www.readbyqxmd.com/read/29281850/cd70-encoded-by-modified-vaccinia-virus-ankara-enhances-cd8-t-cell-dependent-protective-immunity-in-mhc-class-ii-deficient-mice
#5
Barbara Bathke, Juliane Pätzold, Ronny Kassub, Raphael Giessel, Kerstin Lämmermann, Maria Hinterberger, Kay Brinkmann, Paul Chaplin, Mark Suter, Hubertus Hochrein, Henning Lauterbach
The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen-presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T cell receptor complex a plethora of co-stimulatory signals not only ensures a proper T cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The TNF receptor/ligand pair CD27/CD70 gained a lot of attraction due to its key role in regulating T cell activation, survival, differentiation, and maintenance, especially in the course of viral infections and cancer...
December 27, 2017: Immunology
https://www.readbyqxmd.com/read/29213269/safety-and-immunogenicity-of-malaria-vectored-vaccines-given-with-routine-expanded-program-on-immunization-vaccines-in-gambian-infants-and-neonates-a-randomized-controlled-trial
#6
Victorine A Mensah, Sophie Roetynck, Ebrima K Kanteh, Georgina Bowyer, Amy Ndaw, Francis Oko, Carly M Bliss, Ya Jankey Jagne, Riccardo Cortese, Alfredo Nicosia, Rachel Roberts, Flavia D'Alessio, Odile Leroy, Babacar Faye, Beate Kampmann, Badara Cisse, Kalifa Bojang, Stephen Gerry, Nicola K Viebig, Alison M Lawrie, Ed Clarke, Egeruan B Imoukhuede, Katie J Ewer, Adrian V S Hill, Muhammed O Afolabi
Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29116169/a-zika-vaccine-targeting-ns1-protein-protects-immunocompetent-adult-mice-in-a-lethal-challenge-model
#7
Aaron C Brault, Arban Domi, Erin M McDonald, Dalit Talmi-Frank, Nathanael McCurley, Rahul Basu, Harriet L Robinson, Michael Hellerstein, Nisha K Duggal, Richard A Bowen, Farshad Guirakhoo
Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens)...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109380/hazard-characterization-of-modified-vaccinia-virus-ankara-vector-what-are-the-knowledge-gaps
#8
REVIEW
Malachy I Okeke, Arinze S Okoli, Diana Diaz, Collins Offor, Taiwo G Oludotun, Morten Tryland, Thomas Bøhn, Ugo Moens
Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, animals and the environment. MVA and recombinant MVA are widely believed to pose low or negligible risk to ecosystem health...
October 29, 2017: Viruses
https://www.readbyqxmd.com/read/29093263/human-vaccination-against-rh5-induces-neutralizing-antimalarial-antibodies-that-inhibit-rh5-invasion-complex-interactions
#9
Ruth O Payne, Sarah E Silk, Sean C Elias, Kazutoyo Miura, Ababacar Diouf, Francis Galaway, Hans de Graaf, Nathan J Brendish, Ian D Poulton, Oliver J Griffiths, Nick J Edwards, Jing Jin, Geneviève M Labbé, Daniel Gw Alanine, Loredana Siani, Stefania Di Marco, Rachel Roberts, Nicky Green, Eleanor Berrie, Andrew S Ishizuka, Carolyn M Nielsen, Martino Bardelli, Frederica D Partey, Michael F Ofori, Lea Barfod, Juliana Wambua, Linda M Murungi, Faith H Osier, Sumi Biswas, James S McCarthy, Angela M Minassian, Rebecca Ashfield, Nicola K Viebig, Fay L Nugent, Alexander D Douglas, Johan Vekemans, Gavin J Wright, Saul N Faust, Adrian Vs Hill, Carole A Long, Alison M Lawrie, Simon J Draper
The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. We report on the first clinical trial to our knowledge to assess the RH5 antigen - a dose-escalation phase Ia study in 24 healthy, malaria-naive adult volunteers...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29065142/safety-and-vaccine-induced-hiv-1-immune-responses-in-healthy-volunteers-following-a-late-mva-b-boost-4-years-after-the-last-immunization
#10
RANDOMIZED CONTROLLED TRIAL
Alberto C Guardo, Carmen Elena Gómez, Vicens Díaz-Brito, Judit Pich, Joan Albert Arnaiz, Beatriz Perdiguero, Juan García-Arriaza, Nuria González, Carlos O S Sorzano, Laura Jiménez, José Luis Jiménez, María Ángeles Muñoz-Fernández, José M Gatell, José Alcamí, Mariano Esteban, Juan Carlos López Bernaldo de Quirós, Felipe García, Montserrat Plana
BACKGROUND: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization...
2017: PloS One
https://www.readbyqxmd.com/read/29021394/hiv-1-gp120-protein-and-mvagp140-boost-immunogens-increase-immunogenicity-of-a-dna-mva-hiv-1-vaccine
#11
Xiaoying Shen, Rahul Basu, Sheetal Sawant, David Beaumont, Sue Fen Kwa, Celia LaBranche, Kelly E Seaton, Nicole L Yates, David C Montefiori, Guido Ferrari, Linda S Wyatt, Bernard Moss, S Munir Alam, Barton F Haynes, Georgia D Tomaras, Harriet L Robinson
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia Ankara (MVA) expressing HIV-1 Env on virus like particles. Here we evaluated whether the addition of a gp120 protein in alum or MVA expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime - MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26 and 40...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020058/hiv-transmitted-founder-vaccines-elicit-autologous-tier-2-neutralizing-antibodies-for-the-cd4-binding-site
#12
Nathanael P McCurley, Arban Domi, Rahul Basu, Kevin O Saunders, Celia C LaBranche, David C Montefiori, Barton F Haynes, Harriet L Robinson
Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30)...
2017: PloS One
https://www.readbyqxmd.com/read/28989096/exploiting-2a-peptides-to-elicit-potent-neutralizing-antibodies-by-a-multi-subunit-herpesvirus-glycoprotein-complex
#13
Felix Wussow, Flavia Chiuppesi, Zhuo Meng, Joy Martinez, Jenny Nguyen, Peter A Barry, Don J Diamond
Neutralizing antibodies (NAb) interfering with glycoprotein complex-mediated virus entry into host cells are thought to contribute to the protection against herpesvirus infection. However, using herpesvirus glycoprotein complexes as vaccine antigens can be complicated by the necessity of expressing multiple subunits simultaneously to allow efficient complex assembly and formation of conformational NAb epitopes. By using a novel bacterial artificial chromosome (BAC) clone of the clinically deployable Modified Vaccinia Ankara (MVA) vector and exploiting ribosomal skipping mediated by 2A peptides, MVA vectors were generated that expressed self-processing subunits of the human cytomegalovirus (HCMV) pentamer complex (PC) composed of gH, gL, UL128, UL130, and UL131A...
January 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/28987424/strategies-to-obtain-multiple-recombinant-modified-vaccinia-ankara-vectors-applications-to-influenza-vaccines
#14
Andrea Barbieri, Maddalena Panigada, Elisa Soprana, Giuseppina Di Mario, Francesco Gubinelli, Valentina Bernasconi, Marta Recagni, Isabella Donatelli, Maria R Castrucci, Antonio G Siccardi
As a vaccination vector, MVA has been widely investigated both in animal models and humans. The construction of recombinant MVA (rMVA) relies on homologous recombination between an acceptor virus and a donor plasmid in infected/transfected permissive cells. Our construction strategy "Red-to-Green gene swapping" - based on the exchange of two fluorescent markers within the flanking regions of MVA deletion ΔIII, coupled to fluorescence activated cell sorting - is here extended to a second insertion site, within the flanking regions of MVA deletion ΔVI...
January 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/28969431/intradermal-hiv-1-dna-immunization-using-needle-free-zetajet-sup-tm-sup-injection-followed-by-hiv-modified-vaccinia-virus-ankara-vaccination-is-safe-and-immunogenic-in-mozambican-young-adults-a-phase-i-randomized-controlled-trial
#15
Edna Omar Viegas, Nelson Tembe, Charlotta Nilsson, Bindiya Meggi, Cremildo Maueia, Orvalho Augusto, Richard Stout, Gabriella Scarlatti, Guido Ferrari, Patricia Earl, Britta Wahren, Sören Andersson, Merlin Robb, Nafissa Osman, Gunnel Biberfeld, Ilesh Jani, Eric Sandström
We assessed safety and immunogenicity of HIV-DNA priming using Zetajet<sup>TM</sup>, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 µg (n = 10; 2 x 0.1mL) or 1200 µg (n = 10; 2 x 0.2mL) of HIV-DNA (3 mg/mL), followed by two boosts of 10<sup>8</sup>pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups...
October 2, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#16
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28846477/modified-vaccinia-virus-ankara-based-vaccines-in-the-era-of-personalized-immunotherapy-of-cancer
#17
Kaïdre Bendjama, Eric Quemeneur
While interest in immunotherapies is renewed by the successful introduction of immune checkpoint blocking agent in the clinic, advances in genome sequencing are opening new possibilities in the design of increasingly personalized vaccines. Personalization of medicine can now be realistically contemplated at the single patient level. Unlike the previous generation of cancer vaccines, neoantigen directed vaccines would target truly specific tumor antigens resulting from acquired tumor genome mutations. Immune response induced by this next generation vaccine would not be subject to self-tolerance and will likely result to enhanced efficacy...
September 2, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28838267/immunogenicity-and-efficacy-of-dna-mva-hiv-vaccines-in-rhesus-macaque-models
#18
Lynette Siv Chea, Rama Rao Amara
Despite 30 years of research on HIV, a vaccine to prevent infection and limit disease progression remains elusive. The RV144 trial showed moderate, but significant protection in humans and highlighted the contribution of antibody responses directed against HIV envelope as an important immune correlate for protection. Efforts to further build upon the progress include the use of a heterologous prime-boost regimen using DNA as the priming agent and the attenuated vaccinia virus, Modified Vaccinia Ankara (MVA), as a boosting vector for generating protective HIV-specific immunity...
September 4, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28837572/efficient-and-stable-production-of-modified-vaccinia-ankara-virus-in-two-stage-semi-continuous-and-in-continuous-stirred-tank-cultivation-systems
#19
Felipe Tapia, Ingo Jordan, Yvonne Genzel, Udo Reichl
One important aim in cell culture-based viral vaccine and vector production is the implementation of continuous processes. Such a development has the potential to reduce costs of vaccine manufacturing as volumetric productivity is increased and the manufacturing footprint is reduced. In this work, continuous production of Modified Vaccinia Ankara (MVA) virus was investigated. First, a semi-continuous two-stage cultivation system consisting of two shaker flasks in series was established as a small-scale approach...
2017: PloS One
https://www.readbyqxmd.com/read/28819261/modified-vaccinia-virus-ankara-preferentially-targets-antigen-presenting-cells-in-vitro-ex-vivo-and-in-vivo
#20
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
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