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https://www.readbyqxmd.com/read/28630358/assessing-the-safety-and-immunogenicity-of-recombinant-vesicular-stomatitis-virus-ebola-vaccine-in-healthy-adults-a-randomized-clinical-trial
#1
May S ElSherif, Catherine Brown, Donna MacKinnon-Cameron, Li Li, Trina Racine, Judie Alimonti, Thomas L Rudge, Carol Sabourin, Peter Silvera, Jay W Hooper, Steven A Kwilas, Nicole Kilgore, Christopher Badorrek, W Jay Ramsey, D Gray Heppner, Tracy Kemp, Thomas P Monath, Teresa Nowak, Shelly A McNeil, Joanne M Langley, Scott A Halperin
BACKGROUND: The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans. METHODS: In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo...
June 19, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28628441/novel-retinal-lesion-in-ebola-survivors-sierra-leone-2016
#2
Paul J Steptoe, Janet T Scott, Julia M Baxter, Craig K Parkes, Rahul Dwivedi, Gabriela Czanner, Matthew J Vandy, Fayiah Momorie, Alimamy D Fornah, Patrick Komba, Jade Richards, Foday Sahr, Nicholas A V Beare, Malcolm G Semple
We conducted a case-control study in Freetown, Sierra Leone, to investigate ocular signs in Ebola virus disease (EVD) survivors. A total of 82 EVD survivors with ocular symptoms and 105 controls from asymptomatic civilian and military personnel and symptomatic eye clinic attendees underwent ophthalmic examination, including widefield retinal imaging. Snellen visual acuity was <6/7.5 in 75.6% (97.5% CI 63%-85.7%) of EVD survivors and 75.5% (97.5% CI 59.1%-87.9%) of controls. Unilateral white cataracts were present in 7...
July 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28606591/safety-and-immunogenicity-of-the-rvsv%C3%A2-g-zebov-gp-ebola-virus-vaccine-candidate-in-healthy-adults-a-phase-1b-randomised-multicentre-double-blind-placebo-controlled-dose-response-study
#3
D Gray Heppner, Tracy L Kemp, Brian K Martin, William J Ramsey, Richard Nichols, Emily J Dasen, Charles J Link, Rituparna Das, Zhi Jin Xu, Eric A Sheldon, Teresa A Nowak, Thomas P Monath
BACKGROUND: The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. METHODS: In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection...
June 9, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28592526/novel-cross-reactive-monoclonal-antibodies-against-ebolavirus-glycoproteins-show-protection-in-a-murine-challenge-model
#4
Jim Duehr, Teddy John Wohlbold, Lisa Oestereich, Veronika Chromikova, Fatima Amanat, Madhusudan Rajendran, Sergio Gomez-Medina, Ignacio Mena, Benjamin R TenOever, Adolfo García-Sastre, Christopher F Basler, Cesar Munoz-Fontela, Florian Krammer
Out of an estimated 31,100 cases since its discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (∼11,000) of these occurred during the 2013-2016 West African epidemic. Three out of five species in the genus are known to cause Ebola Virus Disease in humans. Several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. However, there is still a paucity of monoclonal antibodies that can cross-react between the glycoproteins of different ebolavirus species and the mechanism of these monoclonal antibody therapeutics are still not understood in detail...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28574091/macrocyclic-peptide-inhibitors-for-the-protein-protein-interaction-of-zaire-ebola-virus-protein-24-and-karyopherin-alpha-5
#5
Xiao Song, Lu-Yi Lu, Toby Passioura, Hiroaki Suga
Ebola virus infection leads to severe hemorrhagic fever in human and non-human primates with an average case fatality rate of 50%. To date, numerous potential therapies are in development, but FDA-approved drugs or vaccines are yet unavailable. Ebola viral protein 24 (VP24) is a multifunctional protein that plays critical roles in the pathogenesis of Ebola virus infection, e.g. innate immune suppression by blocking the interaction between KPNA and PY-STAT1. Here we report macrocyclic peptide inhibitors of the VP24-KPNA5 protein-protein interaction (PPI) by means of the RaPID (Random non-standard Peptides Integrated Discovery) system...
June 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28573609/ebolavirus-an-overview-of-molecular-and-clinical-pathogenesis
#6
Veronica Vine, Dana P Scott, Heinz Feldmann
Ebolaviruses cause severe, often fatal hemorrhagic fever in Central, East, and West Africa. Until recently, they have been viewed as rare but highly pathogenic infections with regional, but limited, global public health impact. This view has changed with the emergence of the first epidemic of Ebola hemorrhagic fever in West Africa. In this chapter we provide an introduction of the pathogenesis of ebolaviruses as well as a description of clinical disease features. We also describe the current animal models used in ebolavirus research, detailing each model's unique strengths and weaknesses...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28549145/six-month-safety-data-of-recombinant-vesicular-stomatitis-virus-zaire-ebola-virus-envelope-glycoprotein-vaccine-in-a-phase-3-double-blind-placebo-controlled-randomized-study-in-healthy-adults
#7
Scott A Halperin, Jose R Arribas, Richard Rupp, Charles P Andrews, Laurence Chu, Rituparna Das, Jakub K Simon, Matthew T Onorato, Kenneth Liu, Jason Martin, Frans A Helmond
Background.: This study (NCT02503202) evaluated the safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP). Methods.: Overall, 1197 subjects were randomized 2:2:2:2:1; 1194 were vaccinated with 1 dose of 1 of 3 lots of rVSVΔG- ZEBOV-GP (2 × 107 plaque-forming units [pfu], n = 797; combined-lots group), a single high-dose lot of rVSVΔG-ZEBOV-GP (1 × 108 pfu, n = 264; high-dose group), or placebo (n = 133)...
May 26, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28539437/spontaneous-mutation-at-amino-acid-544-of-the-ebola-glycoprotein-potentiates-virus-entry-and-selection-in-tissue-culture
#8
John B Ruedas, Jason Ladner, Chelsea R Ettinger, Suryaram Gummuluru, Gustavo Palacios, John H Connor
Ebolaviruses have a surface glycoprotein (GP1,2) required for virus attachment and entry into cells. Mutations affecting GP1,2 functions can alter virus growth properties. We generated a recombinant vesicular stomatitis virus encoding Ebola Virus Makona variant GP1,2 (rVSV-MAK-GP) and observed emergence of a T544I mutation in the Makona GP1,2 gene during tissue culture passage in certain cell lines. The T544I mutation emerged within two passages when VSV-MAK-GP was grown on Vero E6, Vero, and BS-C-1 cells but not when it was passaged on Huh7 and HepG2 cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28505570/clinical-evaluation-of-the-biofire-filmarray-%C3%A2-biothreat-e-test-for-the-diagnosis-of-ebola-virus-disease-in-guinea
#9
Françoise Gay-Andrieu, N'Fally Magassouba, Valentina Picot, Cynthia L Phillips, Christophe N Peyrefitte, Brigitte Dacosta, Ahmadou Doré, Fode Kourouma, Véronique Ligeon-Ligeonnet, Corentin Gauby, Christophe Longuet, Matt Scullion, Ousmane Faye, Jean Louis Machuron, Mark Miller
BACKGROUND: The recent West Africa Ebola outbreak highlighted the need to provide access to rapid, safe and reliable Ebola Virus Disease diagnostics. OBJECTIVES: The objective of this field study was to assess the clinical performance of the FilmArray(®) BioThreat-E test for the detection of Ebola Zaïre virus in whole blood in symptomatic patients suspected of Ebola Virus Disease in Conakry (Guinea) from March to July 2015. STUDY DESIGN: The BioThreat-E test was compared to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency context: an in-house developed quantitative one-step RT-PCR adapted from the Weidmann technique, and the RealStar(®) Filovirus RT-PCR Kit 1...
May 1, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28482272/screening-of-commercial-cyclic-peptide-conjugated-to-hiv-1-tat-peptide-as-inhibitor-of-n-terminal-heptad-repeat-glycoprotein-2-ectodomain-ebola-virus-through-in-silico-analysis
#10
Usman Sumo Friend Tambunan, Ahmad Husein Alkaff, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Djati Kerami
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism...
April 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28466035/analysis-of-ebola-virus-polymerase-domains-to-find-strain-specific-differences-and-to-gain-insight-on-their-pathogenicity
#11
Seema Patel, Snigdha Patel
Ebola virus, a member of the family Filoviridae has caused immense morbidity and mortality in recent times, especially in West Africa. The infection characterized by chills, fever, diarrhea, and myalgia can progress to hemorrhage and death. Hence, it is a high priority area to better understand its biology in order to expedite vaccine development pipelines. In this regard, this study analyzes the domains in RNA polymerase of fifteen publicly-available Ebola isolates belonging to three strains (Zaire, Sudan and Reston)...
September 2016: Virusdisease
https://www.readbyqxmd.com/read/28431160/editorial-to-6-month-safety-data-of-ebola-zaire-vaccine-rvsv%C3%AE-g-zebov-gp-in-a-phase-iii-double-blind-placebo-controlled-randomized-study-in-healthy-adults
#12
Matthias J Schnell
No abstract text is available yet for this article.
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28412830/expression-and-immunogenicity-of-vp40-protein-of-zebov
#13
Yinbiao Wang, Xiao Liu, Ling Tao, Pengwei Xu, Xia Gao, Huijun Li, Zhongzhi Yang, Weidong Wu
BACKGROUND: EBOV outbreaks continue to threaten the world due to the absence of effective vaccines and therapeutics. Easy-to-use and rapid diagnostic tests for EBOV are highly desired for prevention and control of the EVD epidemic. METHODS: Escherichia coli expression system was used to express VP40 protein of Zaire Ebola virus (ZEBOV) as water-soluble protein upon optimization of temperature, time, and IPTG concentration. VP40 protein was purified through Ni-NTA affinity chromatography and applied to immunize rabbits for immunogenicity analysis...
April 2017: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/28404856/a-dose-dependent-plasma-signature-of-the-safety-and-immunogenicity-of-the-rvsv-ebola-vaccine-in-europe-and-africa
#14
Angela Huttner, Christophe Combescure, Stéphane Grillet, Mariëlle C Haks, Edwin Quinten, Christine Modoux, Selidji Todagbe Agnandji, Jessica Brosnahan, Julie-Anne Dayer, Ali M Harandi, Laurent Kaiser, Donata Medaglini, Tom Monath, Pascale Roux-Lombard, Peter G Kremsner, Tom H M Ottenhoff, Claire-Anne Siegrist
The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28398679/ebola-virus-disease-and-pregnancy-a-review-of-the-current-knowledge-of-ebola-virus-pathogenesis-maternal-and-neonatal-outcomes
#15
REVIEW
Lisa M Bebell, Titilope Oduyebo, Laura E Riley
The 2014 to 2016 Ebola virus disease (EVD) outbreak in West Africa devastated local health systems and caused thousands of deaths. Historical reports from Zaire ebolavirus outbreaks suggested pregnancy was associated with an increased risk of severe illness and death, with mortality rates from 74 to 100%. In total, 111 cases of pregnant patients with EVD are reported in the literature, with an aggregate maternal mortality of 86%. Pregnancy-specific data published from the recent outbreak include four small descriptive cohort studies and five case reports...
March 15, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28389867/expression-of-the-vp40-antigen-from-the-zaire-ebolavirus-in-tobacco-plants
#16
Elizabeth Monreal-Escalante, Abel A Ramos-Vega, Jorge A Salazar-González, Bernardo Bañuelos-Hernández, Carlos Angulo, Sergio Rosales-Mendoza
The plant cell is able to produce the VP40 antigen from the Zaire ebolavirus , retaining the antigenicity and the ability to induce immune responses in BALB/c mice. The recent Ebola outbreak evidenced the need for having vaccines approved for human use. Herein we report the expression of the VP40 antigen from the Ebola virus as an initial effort in the development of a plant-made vaccine that could offer the advantages of being cheap and scalable, which is proposed to overcome the rapid need for having vaccines to deal with future outbreaks...
April 7, 2017: Planta
https://www.readbyqxmd.com/read/28356221/rapid-detection-of-all-known-ebolavirus-species-by-reverse-transcription-loop-mediated-isothermal-amplification-rt-lamp
#17
Olamide K Oloniniyi, Yohei Kurosaki, Hiroko Miyamoto, Ayato Takada, Jiro Yasuda
Ebola virus disease (EVD), a highly virulent infectious disease caused by ebolaviruses, has a fatality rate of 25-90%. Without a licensed chemotherapeutic agent or vaccine for the treatment and prevention of EVD, control of outbreaks requires accurate and rapid diagnosis of cases. In this study, five sets of six oligonucleotide primers targeting the nucleoprotein gene were designed for specific identification of each of the five ebolavirus species using reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay...
March 27, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28345293/detection-of-zaire-ebolavirus-in-swine-assay-development-and-optimization
#18
B S Pickering, B Collignon, G Smith, P Marszal, G Kobinger, H M Weingartl
Ebolaviruses (family Filoviridae, order Mononegavirales) cause often fatal, haemorrhagic fever in primates including humans. Pigs have been identified as a species susceptible to Reston ebolavirus (RESTV) infection, with indicated transmission to humans in the Philippines; however, their role during Ebola outbreaks in Africa needs to be clarified. To perform surveillance studies, detection of ebolavirus requires a prerequisite validation of viral RNA and antibody detection methods in swine samples. These diagnostic tests also need to be suitable for deployment to low-level containment laboratories...
March 27, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28332721/rapid-detection-and-quantification-of-ebola-zaire-virus-by-one-step-real-time-quantitative-reverse-transcription-polymerase-chain-reaction
#19
Young-Tae Ro, Anysha Ticer, Ricardo Carrion, Jean L Patterson
Given that Ebola virus causes severe hemorrhagic fever in humans with mortality rates as high as 90%, rapid and accurate detection of this virus is essential both for controlling infection and preventing further transmission. Here, a one-step qRT-PCR assay for rapid and quantitative detection of an Ebola Zaire strain using GP, VP24 or VP40 genes as a target is introduced. Routine assay conditions for hydrolysis probe detection were established from the manufacturer's protocol used in the assays. The analytical specificity and sensitivity of each assay was evaluated using in vitro synthesized viral RNA transcripts...
April 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28242293/lyophilized-visually-readable-loop-mediated-isothermal-reverse-transcriptase-nucleic-acid-amplification-test-for-detection-ebola-zaire-rna
#20
Christoph Carter, Kevan Akrami, Drew Hall, Davey Smith, Eliah Aronoff-Spencer
Recent viral outbreaks highlight the need for reliable, yet broadly deployable diagnostics for detection of epidemic and emerging pathogens. In this study we designed and optimized methods to visually detect viral nucleic acid by isothermal amplification and SYBR dye intercalation. We designed and tested loop-mediated isothermal amplification (LAMP) primers and lyophilized reactions to optimize the detection of Zaire Ebola Virus (ZEBOV) and further evolved the LAMP platform to allow room-temperature storage for deployment in resource limited settings...
February 24, 2017: Journal of Virological Methods
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