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https://www.readbyqxmd.com/read/29206076/assessment-of-the-ability-of-v920-recombinant-vesicular-stomatitis-zaire-ebolavirus-vaccine-to-replicate-in-relevant-arthropod-cell-cultures-and-vector-species
#1
Nicholas A Bergren, Megan R Miller, Thomas P Monath, Rebekah C Kading
V920, rVSVΔG-ZEBOV-GP, is a recombinant vesicular stomatitis-Zaire ebolavirus vaccine which has shown an acceptable safety profile and provides a protective immune response against Ebola virus disease (EVD) induced by Zaire ebolavirus in humans. The purpose of this study was to determine whether the V920 vaccine is capable of replicating in arthropod cell cultures of relevant vector species and of replicating in live mosquitoes. While the V920 vaccine replicated well in Vero cells, no replication was observed in Anopheles or Aedes mosquito, Culicoides biting midge, or Lutzomyia sand fly cells, nor in live Culex or Aedes mosquitoes following exposure through intrathoracic inoculation or feeding on a high-titer infectious blood meal...
December 5, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29199040/progress-towards-a-vaccine-against-ebola-to-meet-emergency-medical-countermeasure-needs
#2
Daniel N Wolfe, Amanda G Zarrabian, Gary L Disbrow, Eric M Espeland
The Ebola virus epidemic in West Africa proved to be the largest in the history of filovirus outbreaks, causing the World Health Organization to declare a public health emergency of international concern in August of 2014. In collaboration with domestic and international partners, the Biomedical Advanced Research and Development Authority (BARDA) initiated several vaccine development projects in support of the overall response efforts. The urgency associated with the epidemic triggered the clinical evaluation of lead vaccine candidates starting in late 2014...
November 30, 2017: Vaccine
https://www.readbyqxmd.com/read/29142131/single-dose-trivalent-vesiculovax-vaccine-protects-macaques-from-lethal-ebolavirus-and-marburgvirus-challenge
#3
Demetrius Matassov, Chad E Mire, Theresa Latham, Joan B Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N Agans, Dean J Kobs, Morgan Q S Wendling, Amanda Burnaugh, Thomas L Rudge, Carol L Sabourin, Michael A Egan, David K Clarke, Thomas W Geisbert, John H Eldridge
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29140409/ebolavirus-interferon-antagonists-protein-interaction-perspectives-to-combat-pathogenesis
#4
Anupam Banerjee, Abantika Pal, Debnath Pal, Pralay Mitra
Zaire ebolavirus, one of the most pathogenic species of Ebolavirus, is a significant threat to the human community being both highly infectious and lethal. The viral proteins (VPs), specifically VP24 and VP35, antagonize the interferon (IFN) proteins accountable for human immune response. Several efforts have been made to design vaccines and therapeutics drugs. However, the success is not encouraging because of limited knowledge about the binding site information of the VPs. Such limitations stem largely from the highly infectious nature of the virus that requires specialized personnel and biosafety laboratories...
November 13, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29123522/transcriptome-analysis-of-circulating-immune-cell-subsets-highlight-the-role-of-monocytes-in-zaire-ebola-virus-makona-pathogenesis
#5
Andrea R Menicucci, Krista Versteeg, Courtney Woolsey, Chad E Mire, Joan B Geisbert, Robert W Cross, Krystle N Agans, Allen Jankeel, Thomas W Geisbert, Ilhem Messaoudi
Existing models of Ebola virus disease (EVD) suggest antigen-presenting cells are initial targets of Zaire ebolavirus (ZEBOV). In vitro studies have shown that ZEBOV infection of monocytes and macrophages results in the production of inflammatory mediators, which may cause lymphocyte apoptosis. However, these findings have not been corroborated by in vivo studies. In this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, T-cells, and B-cells isolated from cynomolgus macaques following infection with ZEBOV-Makona...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29104771/virus-vectored-ebola-vaccines
#6
I V Dolzhikova, E A Tokarskaya, A S Dzharullaeva, A I Tukhvatulin, D V Shcheblyakov, O L Voronina, S I Syromyatnikova, S V Borisevich, V B Pantyukhov, V F Babira, L V Kolobukhina, B S Naroditsky, D Y Logunov, A L Gintsburg
The Ebola virus disease (EVD) is one of the most dangerous infections affecting humans and animals. The first EVD outbreaks occurred in 1976 in Sudan and Zaire. Since then, more than 20 outbreaks have occurred; the largest of which (2014-2016) evolved into an epidemic in West Africa and claimed the lives of more than 11,000 people. Although vaccination is the most effective way to prevent epidemics, there was no licensed vaccine for EVD at the beginning of the latest outbreak. The development of the first vaccines for EVD started in 1980 and has come a long technological way, from inactivated to genetically engineered vaccines based on recombinant viral vectors...
July 2017: Acta Naturae
https://www.readbyqxmd.com/read/28985239/safety-and-immunogenicity-of-rvsv%C3%AE-g-zebov-gp-ebola-vaccine-in-adults-and-children-in-lambar%C3%A3-n%C3%A3-gabon-a-phase-i-randomised-trial
#7
RANDOMIZED CONTROLLED TRIAL
Selidji T Agnandji, José F Fernandes, Emmanuel B Bache, Régis M Obiang Mba, Jessica S Brosnahan, Lumeka Kabwende, Paul Pitzinger, Pieter Staarink, Marguerite Massinga-Loembe, Verena Krähling, Nadine Biedenkopf, Sarah Katharina Fehling, Thomas Strecker, David J Clark, Henry M Staines, Jay W Hooper, Peter Silvera, Vasee Moorthy, Marie-Paule Kieny, Akim A Adegnika, Martin P Grobusch, Stephan Becker, Michael Ramharter, Benjamin Mordmüller, Bertrand Lell, Sanjeev Krishna, Peter G Kremsner
BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. METHODS AND FINDINGS: A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection...
October 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28915404/dynamic-phosphorylation-of-ebola-virus-vp30-in-np-induced-inclusion-bodies
#8
Clemens Lier, Stephan Becker, Nadine Biedenkopf
Zaire Ebolavirus (EBOV) causes a severe feverish disease with high case fatality rates. Transcription of EBOV is dependent on the activity of the nucleocapsid protein VP30 which represents an essential viral transcription factor. Activity of VP30 is regulated via phosphorylation at six N-terminal serine residues. Recent data demonstrated that dynamic phosphorylation and dephosphorylation of serine residue 29 is essential for transcriptional support activity of VP30. To analyze the spatio/temporal dynamics of VP30 phosphorylation, we generated a peptide antibody recognizing specifically VP30 phosphorylated at serine 29...
December 2017: Virology
https://www.readbyqxmd.com/read/28878074/cooperation-of-the-ebola-virus-proteins-vp40-and-gp1-2-with-bst2-to-activate-nf-%C3%AE%C2%BAb-independently-of-virus-like-particle-trapping
#9
Maryan G Rizk, Christopher F Basler, John Guatelli
BST2 is a host protein with dual functions in response to viral infections: it traps newly assembled enveloped virions at the plasma membrane in infected cells, and it induces NF-κB activity, especially in the context of retroviral assembly. In this study, we examined whether Ebola virus proteins affect BST2-mediated induction of NF-κB. We found that the Ebola virus matrix protein, VP40, and envelope glycoprotein, GP, each cooperate with BST2 to induce NF-κB activity, with maximal activity when all three proteins are expressed...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28852031/infection-with-the-makona-variant-results-in-a-delayed-and-distinct-host-immune-response-compared-to-previous-ebola-virus-variants
#10
Krista Versteeg, Andrea R Menicucci, Courtney Woolsey, Chad E Mire, Joan B Geisbert, Robert W Cross, Krystle N Agans, Daniel Jeske, Ilhem Messaoudi, Thomas W Geisbert
Zaire Ebolavirus (ZEBOV) continues to pose a significant threat to human health as highlighted by the recent epidemic that originated in West Africa and the ongoing outbreak in the Democratic Republic of the Congo. Although the ZEBOV variant responsible for this epidemic (Makona) shares significant genetic similarity with previously identified variants (Kikwit and Mayinga), recent reports suggest slower disease progression in nonhuman primates. However, the pathogenesis caused by the new variant is not fully understood...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822816/genetically-modified-rabies-virus-vectored-ebola-virus-disease-vaccines-are-safe-and-induce-efficacious-immune-responses-in-mice-and-dogs
#11
Lei Shuai, Xijun Wang, Zhiyuan Wen, Jinying Ge, Jinliang Wang, Dandan Zhao, Zhigao Bu
Ebola viruses (EBOVs) are zoonotic pathogens that cause EBOV disease (EVD) with high case fatality in humans. Currently, EVD vaccines are still under development in several countries. Here, we generated two recombinant rabies viruses (RABVs), rERAG333E/ZGP and rERAG333E/SGP, expressing the Zaire EBOV glycoprotein (ZGP) or Sudan EBOV glycoprotein (SGP) gene based on a modified ERA vaccine strain (rERAG333E) vector platform. The recombinant RABVs retained growth properties similar to those of the vector virus in BSR cell culture and efficiently expressed ZGP or SGP...
August 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28795602/immunogenicity-of-the-recombinant-adenovirus-type-5-vector-based-ebola-vaccine-ad5-ebov-expressing-the-glycoprotein-of-the-2014-epidemic-strain-in-mice
#12
Ling Wang, Jing Jing Liu, Yan Kong, Li Hua Hou, Yu Hua Li
The 2014 Ebola outbreak in West Africa has brought great threat to the public health worldwide. Development of Ebola vaccine is urgent. A novel recombinant adenovirus type-5 vector-based Ebola vaccine (Ad5-EBOV) based on the 2014 Zaire Guinea epidemic strain was developed in China. A good safety profile and robust immune response elicited by Ad5-EBOV were confirmed in Phase I and Phase II clinical trial. However, clinical studies of Ebola vaccine are still at an early stage and no solid efficacy data for human beings yet...
August 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28780120/vaccines-against-ebola-virus
#13
Navin Venkatraman, Daniel Silman, Pedro M Folegatti, Adrian V S Hill
We have just witnessed the largest and most devastating outbreak of Ebola virus disease, which highlighted the urgent need for development of an efficacious vaccine that could be used to curtail future outbreaks. Prior to 2014, there had been limited impetus worldwide to develop a vaccine since the virus was first discovered in 1976. Though too many lives were lost during this outbreak, it resulted in the significantly accelerated clinical development of a number of candidate vaccines through an extraordinary collaborative global effort coordinated by the World Health Organisation (WHO) and involving a number of companies, trial centres, funders, global stakeholders and agencies...
August 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28756560/in-silico-analysis-of-the-cyanobacterial-lectin-scytovirin-new-insights-into-binding-properties
#14
Andrei Santos Siqueira, Alex Ranieri Jerônimo Lima, Rafael Conceição de Souza, Alberdan Silva Santos, João Lídio da Silva Gonçalves Vianez Júnior, Evonnildo Costa Gonçalves
Scytovirin is a lectin isolated from the cyanobacterium Scytonema varium that has shown activity against HIV, SARS coronavirus and Zaire Ebola virus. Its 95 amino acids are divided into two structural domains (SD), the first spanning amino acids 1-48 (SD1) and the second 49-95 (SD2). Interestingly, the domains are nearly identical but differ in their affinities for carbohydrates. With the aim of enhancing understanding of the binding properties of scytovirin, we performed molecular dynamics (MD) simulations of scytovirin complexed with Man4...
August 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28752209/plasma-lipidome-analysis-by-liquid-chromatography-high-resolution-mass-spectrometry-and-ion-mobility-of-hypertriglyceridemic-patients-on-extended-release-nicotinic-acid-a-pilot-study
#15
Véronique Ferchaud-Roucher, Mikaël Croyal, Thomas Moyon, Yassine Zair, Michel Krempf, Khadija Ouguerram
BACKGROUND: Plasma high triacylglycerols and low HDL-C concentration are associated with increased cardiovascular events. Extended-release nicotinic acid (ERN) was shown to reduce plasma triacylglycerols and total cholesterol but also to markedly increase high-density lipoprotein-cholesterol (HDL-C). No data on the effect of ERN on different species of triacylglycerol, cholesteryl ester, and phospholipids are available. In this study, we applied a nontargeted lipidomic approach to investigate the plasma and lipoproteins lipids profile of hypertriglyceridemic patients treated with ERN or a placebo in order to identify new lipids markers associated with this treatment...
July 28, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28713333/algevir-an-expression-system-for-microalgae-based-on-viral-vectors
#16
Bernardo Bañuelos-Hernández, Elizabeth Monreal-Escalante, Omar González-Ortega, Carlos Angulo, Sergio Rosales-Mendoza
The use of recombinant algae for the production of valuable compounds is opening promising biotechnological applications. However, the development of efficient expression approaches is still needed to expand the exploitation of microalgae in biotechnology. Herein, the concept of using viral expression vectors in microalgae was explored for the first time. An inducible geminiviral vector leading to Rep-mediated replication of the expression cassette allowed the production of antigenic proteins at high levels...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28666874/anti-dengue-virus-activity-of-scytovirin-and-evaluation-of-point-mutation-effects-by-molecular-dynamics-and-binding-free-energy-calculations
#17
Andrei Santos Siqueira, Alex Ranieri Jerônimo Lima, Rafael Conceição de Souza, Alberdan Silva Santos, João Lídio da Silva Gonçalves Vianez Júnior, Evonnildo Costa Gonçalves
The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28663587/challenge-of-liquid-stressed-protective-materials-and-environmental-persistence-of-ebola-virus
#18
Aidan M Nikiforuk, Todd A Cutts, Steven S Theriault, Bradley W M Cook
After the largest Ebola virus outbreak in history, experts have attempted to answer how the Zaire ebolavirus species emerged in West Africa and caused chains of human-to-human transmission. The widespread and untimely infection of Health Care Workers (HCW) in the affected countries accelerated spread of the virus within the community. Among the reasons attributed to this trend, it must be considered that HCW were exposed to the virus in their occupational environment. The contribution of environmental conditions to the spread of Ebola in West Africa was examined by investigating the effect of temperature/humidity on the virus's environmental persistence and by modeling if saturation (liquid stress) allows for penetration of Ebola virus through personal protective equipment (PPE)...
June 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28647166/clinical-development-of-a-recombinant-ebola-vaccine-in-the-midst-of-an-unprecedented-epidemic
#19
Beth-Ann G Coller, Jeffrey Blue, Rituparna Das, Sheri Dubey, Lynn Finelli, Swati Gupta, Frans Helmond, Rebecca J Grant-Klein, Kenneth Liu, Jakub Simon, Sean Troth, Susan VanRheenen, Julie Waterbury, Ashley Wivel, Jayanthi Wolf, D Gray Heppner, Tracy Kemp, Rick Nichols, Thomas P Monath
The 2014-2016 Ebola outbreak caused over 28,000 cases and 11,000 deaths. Merck & Co. Inc., Kenilworth, NJ USA and NewLink Genetics are working with private and public partners to develop and license an Ebola vaccine that was evaluated extensively during the outbreak. The vaccine referred to as V920 is a recombinant vesicular stomatitis virus (rVSV) in which the VSV-G envelope glycoprotein (GP) is completely replaced by the Zaire ebolavirus GP (rVSVΔG-ZEBOV-GP). Eight Phase I and four Phase II/III clinical trials enrolling approximately 17,000 subjects were conducted in parallel to the outbreak to assess the safety, immunogenicity, and/or efficacy of V920...
June 21, 2017: Vaccine
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
#20
RANDOMIZED CONTROLLED TRIAL
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
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