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Ebola vaccine

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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/28616501/searching-for-animal-models-and-potential-target-species-for-emerging-pathogens-experience-gained-from-middle-east-respiratory-syndrome-mers-coronavirus
#2
REVIEW
Júlia Vergara-Alert, Enric Vidal, Albert Bensaid, Joaquim Segalés
Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013-2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia...
June 2017: One Health
https://www.readbyqxmd.com/read/28615211/vesicular-stomatitis-virus-pseudotyped-with-ebola-virus-glycoprotein-serves-as-a-protective-non-infectious-vaccine-against-ebola-virus-challenge-in-mice
#3
Nicholas J Lennemann, Andrew S Herbert, Rachel Brouillette, Bethany Rhein, Russell A Bakken, Katherine J Perschbacher, Ashley L Cooney, Catherine L Miller-Hunt, Patrick Ten Eyck, Julia Biggins, Gene Olinger, John M Dye, Wendy Maury
The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA-approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28610940/establishment-of-a-research-pharmacy-to-support-ebola-clinical-research-in-liberia
#4
Jerome F Pierson, Matthew Carl Kirchoff, Rev Tijli Tyee, Michael J Montello, Julie K Rhie
OBJECTIVE: This article describes the establishment of a research pharmacy to support the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) vaccine study for Ebola virus disease. SETTING: This article describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia, in 2014 and 2015. PRACTICE INNOVATION: The need for the rapid establishment of infrastructure to support the Liberia-United States joint clinical research partnership in response to the emerging Ebola virus disease provided the opportunity for collaboration among Liberian and U...
June 10, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28606592/advances-in-ebola-virus-vaccination
#5
Elizabeth C Clarke, Steven B Bradfute
No abstract text is available yet for this article.
June 9, 2017: Lancet 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
#6
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
#7
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/28588288/t-cell-dependent-mechanisms-promote-ebola-vlp-induced-antibody-responses-but-are-dispensable-for-vaccine-mediated-protection
#8
Christopher L Cooper, Karen A Martins, Sabrina M Stronsky, David P Langan, Jesse Steffens, Sean Van Tongeren, Sina Bavari
Humoral responses are essential for the protective efficacy of most Ebola virus (EBOV) candidate vaccines; however, the in vivo development of protective anti-EBOV B-cell responses is poorly defined. Here, by using the virus-like particle (VLP) as a model antigen, we demonstrate that humoral responses are generated through follicular B-cell and T-cell-dependent mechanisms in a mouse model of EBOV infection. In addition, we show that the inclusion of the clinical-grade dsRNA adjuvant known as poly-ICLC in VLP vaccinations both augments and sustains germinal center B-cell reactions, antigen-specific B-cell frequencies and anti-EBOV serum titers...
June 7, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28576573/rapid-development-of-vaccines-against-emerging-pathogens-the-replication-deficient-simian-adenovirus-platform-technology
#9
Sarah C Gilbert, George M Warimwe
Despite the fact that there had been multiple small outbreaks of Ebola Virus Disease, when a large outbreak occurred in 2014 there were no vaccines or drugs available for use. Clinical development of multiple candidate vaccines was then initiated in parallel with attempts to contain the outbreak but only one vaccine was eventually tested in a phase III trial. In order to be better prepared for future outbreaks of known human pathogens, platform technologies to accelerate vaccine development should be employed, allowing vaccine developers to take advantage of detailed knowledge of the vaccine platform and facilitating rapid progress to clinical trials and eventually to vaccine stockpiles...
May 30, 2017: Vaccine
https://www.readbyqxmd.com/read/28575582/an-immunoinformatics-derived-dna-vaccine-encoding-human-class-ii-t-cell-epitopes-of-ebola-virus-sudan-virus-and-venezuelan-equine-encephalitis-virus-is-immunogenic-in-hla-transgenic-mice
#10
Callie E Bounds, Frances E Terry, Leonard Moise, Drew Hannaman, William D Martin, Anne S De Groot, John J Suschak, Lesley C Dupuy, Connie S Schmaljohn
Immunoinformatics tools were used to predict human leukocyte antigen (HLA) Class II-restricted T cell epitopes within the envelope glycoproteins and nucleocapsid proteins of Ebola virus (EBOV) and Sudan virus (SUDV) and the structural proteins of Venezuelan equine encephalitis virus (VEEV). Selected epitopes were tested for binding to soluble HLA molecules representing five Class II alleles (DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, and DRB1*1501). All but one of the 25 tested peptides bound to at least one of the DRB1 alleles, and four of the peptides bound at least moderately or weakly to all five DRB1 alleles...
June 2, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28575034/ebola-virus-disease-contact-tracing-activities-lessons-learned-and-best-practices-during-the-duport-road-outbreak-in-monrovia-liberia-november-2015
#11
Caitlin M Wolfe, Esther L Hamblion, Jacqueline Schulte, Parker Williams, Augustine Koryon, Jonathan Enders, Varlee Sanor, Yatta Wapoe, Dash Kwayon, David J Blackley, Anthony S Laney, Emily J Weston, Emily K Dokubo, Gloria Davies-Wayne, Annika Wendland, Valerie T S Daw, Mehboob Badini, Peter Clement, Nuha Mahmoud, Desmond Williams, Alex Gasasira, Tolbert G Nyenswah, Mosoka Fallah
BACKGROUND: Contact tracing is one of the key response activities necessary for halting Ebola Virus Disease (EVD) transmission. Key elements of contact tracing include identification of persons who have been in contact with confirmed EVD cases and careful monitoring for EVD symptoms, but the details of implementation likely influence their effectiveness. In November 2015, several months after a major Ebola outbreak was controlled in Liberia, three members of a family were confirmed positive for EVD in the Duport Road area of Monrovia...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28574091/macrocyclic-peptide-inhibitors-for-the-protein-protein-interaction-of-zaire-ebola-virus-protein-24-and-karyopherin-alpha-5
#12
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/28573629/evaluation-of-ebola-virus-countermeasures-in-guinea-pigs
#13
Andrea Marzi
Ebola virus (EBOV) pathology in humans remains incompletely understood; therefore, a number of rodent and nonhuman primate (NHP) models have been established to study the disease caused by this virus. While the macaque model most accurately recapitulates human disease, rodent models, which display only certain aspects of human disease but are more cost-effective, are widely used for initial screens during EBOV countermeasure development. In particular, mice and guinea pigs were among the first species used for the efficacy testing of EBOV vaccines and therapeutics...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28573628/assessing-antiviral-countermeasures-using-mouse-models-of-ebolavirus-infection
#14
Andrea Kroeker, Bryan D Griffin, Xiangguo Qiu, Gary Kobinger
Mouse models of Ebola virus (EBOV) have demonstrated their utility as important tools for screening the efficacy of candidate therapeutics and vaccines. In this chapter we explain the various mouse models that utilize either wild-type or mouse-adapted EBOV variants.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28573614/modeling-ebolavirus-budding-with-virus-like-particles
#15
Olivier Reynard, Mathieu Mateo
About 15 years ago, several groups initially described the release of virus like particles (VLPs) upon expression of Ebola virus VP40 in mammalian cells. Further development of the protocol later allowed for the dissection of the Ebola virus budding mechanism and for the identification of critical VP40 residues involved in this process. VLPs are now produced routinely in several laboratories as a tool to study virus entry or egress and have even been proposed as vaccine candidates against Ebola virus disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28567113/research-ethics-governance-in-times-of-ebola
#16
Doris Schopper, Raffaella Ravinetto, Lisa Schwartz, Eunice Kamaara, Sunita Sheel, Michael J Segelid, Aasim Ahmad, Angus Dawson, Jerome Singh, Amar Jesani, Ross Upshur
The Médecins Sans Frontières (MSF) ethics review board (ERB) has been solicited in an unprecedented way to provide advice and review research protocols in an 'emergency' mode during the recent Ebola epidemic. Twenty-seven Ebola-related study protocols were reviewed between March 2014 and August 2015, ranging from epidemiological research, to behavioural research, infectivity studies and clinical trials with investigational products at (very) early development stages. This article examines the MSF ERB's experience addressing issues related to both the process of review and substantive ethical issues in this context...
April 2017: Public Health Ethics
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
#17
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/28533207/who-ready-to-deploy-ebola-vaccine-in-disease-outbreak
#18
Anne Gulland
No abstract text is available yet for this article.
May 22, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#19
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#20
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
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