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Modified vaccinia virus ankara

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https://www.readbyqxmd.com/read/29116169/a-zika-vaccine-targeting-ns1-protein-protects-immunocompetent-adult-mice-in-a-lethal-challenge-model
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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/28792942/hiv-1-neutralizing-antibody-induced-by-simian-adenovirus-and-poxvirus-mva-vectored-bg505-native-like-envelope-trimers
#15
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/28771513/a-modified-vaccinia-ankara-vaccine-vector-expressing-a-mosaic-h5-hemagglutinin-reduces-viral-shedding-in-rhesus-macaques
#16
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/28763795/intratumoral-delivery-of-inactivated-modified-vaccinia-virus-ankara-imva-induces-systemic-antitumor-immunity-via-sting-and-batf3-dependent-dendritic-cells
#17
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/28762495/preparation-of-cell-cultures-and-vaccinia-virus-stocks
#18
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
#19
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
#20
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)...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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