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Modified vaccinia virus ankara

L Coughlan, S Sridhar, R Payne, M Edmans, A Milicic, N Venkatraman, B Lugonja, L Clifton, C Qi, P M Folegatti, A M Lawrie, R Roberts, H de Graaf, P Sukhtankar, S N Faust, D J M Lewis, T Lambe, Avs Hill, S C Gilbert
BACKGROUND: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1)...
February 15, 2018: EBioMedicine
Adrián Lázaro-Frías, Sergio Gómez-Medina, Lucas Sánchez-Sampedro, Karl Ljungberg, Mart Ustav, Peter Liljeström, César Muñoz-Fontela, Mariano Esteban, Juan García-Arriaza
Zaire and Sudan ebolavirus species cause a severe disease in humans and non-human primates (NHPs) characterized by high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013-2016 outbreak in West Africa highlighted the need of EVD-specific medical countermeasures. Here, we have generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA), expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs)...
March 7, 2018: Journal of Virology
Michael White, Andrew Freistaedter, Gwendolyn J B Jones, Emmanuel Zervos, Rachel L Roper
Pancreatic cancer is the 5th leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells...
2018: PloS One
Benoit Callendret, Jort Vellinga, Kerstin Wunderlich, Ariane Rodriguez, Robin Steigerwald, Ulrike Dirmeier, Cedric Cheminay, Ariane Volkmann, Trevor Brasel, Ricardo Carrion, Luis D Giavedoni, Jean L Patterson, Chad E Mire, Thomas W Geisbert, Jay W Hooper, Mo Weijtens, Jutta Hartkoorn-Pasma, Jerome Custers, Maria Grazia Pau, Hanneke Schuitemaker, Roland Zahn
The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV)...
2018: PloS One
Jean-Louis Palgen, Nicolas Tchitchek, Jamila Elhmouzi-Younes, Simon Delandre, Inana Namet, Pierre Rosenbaum, Nathalie Dereuddre-Bosquet, Frédéric Martinon, Antonio Cosma, Yves Lévy, Roger Le Grand, Anne-Sophie Beignon
Understanding the innate immune response to vaccination is critical in vaccine design. Here, we studied blood innate myeloid cells after first and second immunization of cynomolgus macaques with the modified vaccinia virus Ankara. The inflammation at the injection site was moderate and resolved faster after the boost. The blood concentration of inflammation markers increased after both injections but was lower after the boost. The numbers of neutrophils, monocytes, and dendritic cells were transiently affected by vaccination, but without any major difference between prime and boost...
February 15, 2018: Scientific Reports
Anne-Marie C Andersson, Melanie Schwerdtfeger, Peter J Holst
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV...
February 11, 2018: Vaccines
Daniel Vázquez-Ramírez, Yvonne Genzel, Ingo Jordan, Volker Sandig, Udo Reichl
Increasing the yield and the productivity in cell culture-based vaccine manufacturing using high-cell-density (HCD) cultivations faces a number of challenges. For example, medium consumption should be low to obtain a very high concentration of viable host cells in an economical way but must be balanced against the requirement that accumulation of toxic metabolites and limitation of nutrients have to be avoided. HCD cultivations should also be optimized to avoid unwanted induction of apoptosis or autophagy during the early phase of virus infection...
February 9, 2018: Vaccine
Dieke van Dinther, Henrike Veninga, Salvador Iborra, Ellen G F Borg, Leoni Hoogterp, Katarzyna Olesek, Marieke R Beijer, Sjoerd T T Schetters, Hakan Kalay, Juan J Garcia-Vallejo, Kees L Franken, Lamin B Cham, Karl S Lang, Yvette van Kooyk, David Sancho, Paul R Crocker, Joke M M den Haan
Splenic CD169+ macrophages are located in the marginal zone to efficiently capture blood-borne pathogens. Here, we investigate the requirements for the induction of CD8+ T cell responses by antigens (Ags) bound by CD169+ macrophages. Upon Ag targeting to CD169+ macrophages, we show that BATF3-dependent CD8α+ dendritic cells (DCs) are crucial for DNGR-1-mediated cross-priming of CD8+ T cell responses. In addition, we demonstrate that CD169, a sialic acid binding lectin involved in cell-cell contact, preferentially binds to CD8α+ DCs and that Ag transfer to CD8α+ DCs and subsequent T cell activation is dependent on the sialic acid-binding capacity of CD169...
February 6, 2018: Cell Reports
Joshua A Eudailey, Maria L Dennis, Morgan E Parker, Bonnie L Phillips, Tori N Huffman, Camden P Bay, Michael G Hudgens, Roger W Wiseman, Justin J Pollara, Genevieve G Fouda, Guido Ferrari, David J Pickup, Pamela A Kozlowski, Koen K A Van Rompay, Kristina De Paris, Sallie R Permar
Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086...
January 2018: MSphere
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
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
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
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
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
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
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
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
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
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
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 virus Ankara (MVA) expressing HIV-1 Env on virus-like particles. In this study, 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...
December 15, 2017: Journal of Virology
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