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Modified vaccinia virus ankara

Anna-Theresa Lülf, Astrid Freudenstein, Lisa Marr, Gerd Sutter, Asisa Volz
In cell culture infections with vaccinia virus the number of counted virus particles is substantially higher than the number of plaques obtained by titration. We found that standard vaccine preparations of recombinant Modified Vaccinia virus Ankara produce only about 20-30% plaque-forming virions in fully permissive cell cultures. To evaluate the biological activity of the non-plaque-forming particles, we generated recombinant viruses expressing fluorescent reporter proteins under transcriptional control of specific viral early and late promoters...
October 11, 2016: Virology
F Husseini, J-P Delord, C Fournel-Federico, J Guitton, P Erbs, M Homerin, C Halluard, C Jemming, C Orange, J-M Limacher, J-E Kurtz
BACKGROUND: TG4023 is a modified vaccinia virus Ankara (MVA) containing the yeast-originated transgene FCU1, expressing cytosine deaminase and uracil phosphoribosyltransferase enzymes that transform the prodrug flucytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluorouridine-5'-monophosphate (5-FUMP), respectively. This first-in-human study aimed to assess the maximum tolerated dose (MTD) of intra-tumoral (IT) TG4023 and the safety, feasibility, and proof-of-concept (PoC) of TG4023/5-FC combination to deliver high 5-FU concentrations in tumors...
September 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Sunil Kannanganat, Linda S Wyatt, Sailaja Gangadhara, Venkatesarlu Chamcha, Lynette S Chea, Pamela A Kozlowski, Celia C LaBranche, Lakshmi Chennareddi, Benton Lawson, Pradeep B J Reddy, Tiffany M Styles, Thomas H Vanderford, David C Montefiori, Bernard Moss, Harriet L Robinson, Rama Rao Amara
We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor α4β7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p < 0...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Ben R Stading, Jorge E Osorio, Andres Velasco-Villa, Michael Smotherman, Brock Kingstad-Bakke, Tonie E Rocke
Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection...
October 17, 2016: Vaccine
Gaudensia Mutua, Bashir Farah, Robert Langat, Jackton Indangasi, Simon Ogola, Brian Onsembe, Jakub T Kopycinski, Peter Hayes, Nicola J Borthwick, Ambreen Ashraf, Len Dally, Burc Barin, Annika Tillander, Jill Gilmour, Jan De Bont, Alison Crook, Drew Hannaman, Josephine H Cox, Omu Anzala, Patricia E Fast, Marie Reilly, Kundai Chinyenze, Walter Jaoko, Tomáš Hanke, The Hiv-Core 004 Study Group
We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the HIV-1 proteome, which are common to most global variants and which, if mutated, cause a replicative fitness loss. Our first clinical trial in low risk HIV-1-negative adults in Oxford demonstrated the principle that naturally mostly subdominant epitopes, when taken out of the context of full-length proteins/virus and delivered by potent regimens involving combinations of simian adenovirus and poxvirus modified vaccinia virus Ankara, can induce robust CD8(+) T cells of broad specificities and functions capable of inhibiting in vitro HIV-1 replication...
2016: Molecular Therapy. Methods & Clinical Development
Arwen F Altenburg, Carolien E van de Sandt, Stella E van Trierum, Heidi L M De Gruyter, Peter R W A van Run, Ron A M Fouchier, Kenny Roose, Xavier Saelens, Asisa Volz, Gerd Sutter, Rory D de Vries, Guus F Rimmelzwaan
: Due to antigenic drift of influenza viruses, seasonal influenza vaccines need to be updated annually. These vaccines are based on predictions of strains likely to circulate in the next season. However, vaccine efficacy is greatly reduced in case of a mismatch between circulating and vaccine strains. Furthermore, novel antigenically distinct influenza viruses are introduced into the human population from animal reservoirs occasionally and may cause pandemic outbreaks. To dampen the impact of seasonal and pandemic influenza, vaccines that induce broadly protective and long lasting immunity are preferred...
August 31, 2016: Journal of Virology
Michaela Ohmer, Arnim Weber, Gerd Sutter, Katrin Ehrhardt, Albert Zimmermann, Georg Häcker
Infection of mammalian cells with viruses often induces apoptosis. How the recognition of viruses leads to apoptosis of the infected cell and which host cell factors regulate this cell death is incompletely understood. In this study, we focussed on two major anti-apoptotic proteins of the host cell, whose abundance and activity are important for cell survival, the Bcl-2-like proteins Mcl-1 and Bcl-XL. During infection of epithelial cells and fibroblasts with modified vaccinia virus Ankara (MVA), Mcl-1 protein levels dropped but the MVA Bcl-2-like protein F1L could replace Mcl-1 functionally; a similar activity was found in vaccinia virus (VACV)-infected cells...
2016: Cell Death & Disease
Leo Swadling, John Halliday, Christabel Kelly, Anthony Brown, Stefania Capone, M Azim Ansari, David Bonsall, Rachel Richardson, Felicity Hartnell, Jane Collier, Virginia Ammendola, Mariarosaria Del Sorbo, Annette Von Delft, Cinzia Traboni, Adrian V S Hill, Stefano Colloca, Alfredo Nicosia, Riccardo Cortese, Paul Klenerman, Antonella Folgori, Eleanor Barnes
An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen...
August 2, 2016: Vaccines
Smita S Iyer, Sailaja Gangadhara, Blandine Victor, Xiaoying Shen, Xuemin Chen, Rafiq Nabi, Sudhir P Kasturi, Michael J Sabula, Celia C Labranche, Pradeep B J Reddy, Georgia D Tomaras, David C Montefiori, Bernard Moss, Paul Spearman, Bali Pulendran, Pamela A Kozlowski, Rama Rao Amara
UNLABELLED: The encouraging results of the RV144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (HIV) vaccine modalities as a strategy to induce protective immunity. Because vaccine-induced protective immunity is critically determined by HIV envelope (Env) conformation, significant efforts are directed toward generating soluble trimeric Env immunogens that assume native structures. Using the simian immunodeficiency virus (SIV)-macaque model, we tested the immunogenicity and efficacy of sequential immunizations with DNA (D), modified vaccinia virus Ankara (MVA) (M), and protein immunogens, all expressing virus-like particles (VLPs) displaying membrane-anchored trimeric Env...
October 1, 2016: Journal of Virology
Tsungai Ivai Jongwe, Ros Chapman, Nicola Douglass, Shivan Chetty, Gerald Chege, Anna-Lise Williamson
Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (GagM) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study...
2016: PloS One
C S Rollier, E J Verschoor, B E Verstrepen, J A R Drexhage, G Paranhos-Baccala, P Liljeström, G Sutter, L Arribillaga, J J Lasarte, B Bartosch, F-L Cosset, G Inchauspe, J L Heeney
Immune responses against multiple epitopes are required for the prevention of Hepatitis C Virus infection, and the progression to Phase I trials of candidates may be guided by comparative immunogenicity studies in non-human primates. Four vectors, DNA, SFV, human serotype 5 adenovirus (HuAd5) and Modified Vaccinia Ankara poxvirus (MVA), all expressing HCV Core, E1, E2 and NS3, were combined in three prime-boost regimen, and their ability to elicit immune responses against HCV antigens in rhesus macaques was explored and compared...
July 14, 2016: Gene Therapy
U Darsow, M Sbornik, S Rombold, K Katzer, F von Sonnenburg, H Behrendt, J Ring
BACKGROUND: Availability of a safe smallpox vaccine may be necessary under certain circumstances. Use of the old life virus vaccine was associated with serious adverse events, particularly in the setting of atopic eczema (AE) and immunodeficiency. Modified virus Ankara (MVA)-BN, a highly attenuated strain of vaccinia virus, was developed for vaccination with improved safety profile. METHODS: A phase 1 study was conducted in 60 subjects without history of smallpox vaccination to gain experience with smallpox vaccination using this strain in healthy and atopic subjects...
June 29, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Richard N Greenberg, Christine M Hay, Jack T Stapleton, Thomas C Marbury, Eva Wagner, Eva Kreitmeir, Siegfried Röesch, Alfred von Krempelhuber, Philip Young, Richard Nichols, Thomas P Meyer, Darja Schmidt, Josef Weigl, Garth Virgin, Nathaly Arndtz-Wiedemann, Paul Chaplin
BACKGROUND: Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56-80 years old population. METHODS: MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart...
2016: PloS One
Stuart D Dowall, Victoria A Graham, Emma Rayner, Laura Hunter, Robert Watson, Irene Taylor, Antony Rule, Miles W Carroll, Roger Hewson
Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. There is no approved vaccine currently available against CCHF. The most promising candidate, which has previously been shown to confer protection in the small animal model, is a modified Vaccinia Ankara virus vector expressing the CCHF viral glycoprotein (MVA-GP). It has been shown that MVA-GP induces both humoral and cellular immunogenicity. In the present study, sera and T-lymphocytes were passively and adoptively transferred into recipient mice prior to challenge with CCHF virus...
2016: PloS One
Mariette F Ducatez, Jens Becker, Astrid Freudenstein, Maxence Delverdier, Mattias Delpont, Gerd Sutter, Jean-Luc Guérin, Asisa Volz
Modified Vaccinia Ankara (MVA) has proven its efficacy as a recombinant vector vaccine for numerous pathogens including influenza virus. The present study aimed at evaluating a recombinant MVA candidate vaccine against low pathogenic avian influenza virus subtype H9N2 in the chicken model. As the high genetic and antigenic diversity of H9N2 viruses increases vaccine design complexity, one strategy to widen the range of vaccine coverage is to use an ancestor sequence. We therefore generated a recombinant MVA encoding for the gene sequence of an ancestral hemagglutinin H9 protein (a computationally derived amino acid sequence of the node of the H9N2 G1 lineage strains was obtained using the ANCESCON program)...
June 30, 2016: Veterinary Microbiology
Attapon Kamlangdee, Brock Kingstad-Bakke, Jorge E Osorio
UNLABELLED: The most effective way to prevent influenza virus infection is via vaccination. However, the constant mutation of influenza viruses due to antigenic drift and shift compromises vaccine efficacy. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. Using the modified vaccinia Ankara (MVA) virus, we had previously generated a recombinant vaccine against highly pathogenic avian influenza virus (H5N1) based on an in silico mosaic approach...
August 1, 2016: Journal of Virology
Agricola Joachim, Asli Bauer, Sarah Joseph, Christof Geldmacher, Patricia J Munseri, Said Aboud, Marco Missanga, Philipp Mann, Britta Wahren, Guido Ferrari, Victoria R Polonis, Merlin L Robb, Jonathan Weber, Roger Tatoud, Leonard Maboko, Michael Hoelscher, Eligius F Lyamuya, Gunnel Biberfeld, Eric Sandström, Arne Kroidl, Muhammad Bakari, Charlotta Nilsson, Sheena McCormack
BACKGROUND: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). METHODS: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination...
2016: PloS One
David Pejoski, Nicolas Tchitchek, André Rodriguez Pozo, Jamila Elhmouzi-Younes, Rahima Yousfi-Bogniaho, Christine Rogez-Kreuz, Pascal Clayette, Nathalie Dereuddre-Bosquet, Yves Lévy, Antonio Cosma, Roger Le Grand, Anne-Sophie Beignon
Broadening our understanding of the abundance and phenotype of B cell subsets that are induced or perturbed by exogenous Ags will improve the vaccine evaluation process. Mass cytometry (CyTOF) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. We designed a panel of CyTOF Abs to compare the B cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immunization with modified vaccinia virus Ankara...
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Dorothy I Jones, Charles E McGee, Christopher J Sample, Gregory D Sempowski, David J Pickup, Herman F Staats
Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination.
July 2016: Clinical and Vaccine Immunology: CVI
Iain D Milligan, Malick M Gibani, Richard Sewell, Elizabeth A Clutterbuck, Danielle Campbell, Emma Plested, Elizabeth Nuthall, Merryn Voysey, Laura Silva-Reyes, M Juliana McElrath, Stephen C De Rosa, Nicole Frahm, Kristen W Cohen, Georgi Shukarev, Nicola Orzabal, Wilbert van Duijnhoven, Carla Truyers, Nora Bachmayer, Daniel Splinter, Nathaly Samy, Maria Grazia Pau, Hanneke Schuitemaker, Kerstin Luhn, Benoit Callendret, Johan Van Hoof, Macaya Douoguih, Katie Ewer, Brian Angus, Andrew J Pollard, Matthew D Snape
IMPORTANCE: Developing effective vaccines against Ebola virus is a global priority. OBJECTIVE: To evaluate an adenovirus type 26 vector vaccine encoding Ebola glycoprotein (Ad26.ZEBOV) and a modified vaccinia Ankara vector vaccine, encoding glycoproteins from Ebola virus, Sudan virus, Marburg virus, and Tai Forest virus nucleoprotein (MVA-BN-Filo). DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized, placebo-controlled, observer-blind, phase 1 trial performed in Oxford, United Kingdom, enrolling healthy 18- to 50-year-olds from December 2014; 8-month follow-up was completed October 2015...
April 19, 2016: JAMA: the Journal of the American Medical Association
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