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Karnail Singh, Bishal Marasini, Xuemin Chen, Paul Spearman
Ebolaviruses are highly virulent pathogens that cause Ebola viral disease (EVD). Data from non-human primate (NHP) models and from human survivors of EVD suggest that anti-Ebola antibodies play an integral role in protection. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potential mechanism through which anti-Ebola antibodies may mediate protection. We developed a robust Ebola-specific ADCC assay for use in ongoing trials of Ebola vaccines. Stable cell lines for inducible Zaire ebolavirus glycoprotein (EBOV GP) expression were developed to provide a uniform source of target cells in the assay, and were combined with an existing human natural killer (NK) cell line as the effector cell...
June 9, 2018: Journal of Immunological Methods
Yupeng Feng, Chufang Li, Peiyu Hu, Qian Wang, Xuehua Zheng, Yongkun Zhao, Yi Shi, Songtao Yang, Changhua Yi, Ying Feng, Chunxiu Wu, Linbing Qu, Wei Xu, Yao Li, Caijun Sun, Fu Geroge Gao, Xianzhu Xia, Liqiang Feng, Ling Chen
Ebolavirus vaccines based on several adenoviral vectors have been investigated in preclinical studies and clinical trials. The use of adenovirus serotype 2 as a vector for ebolavirus vaccine has not been reported. Herein, we generated rAd2-ZGP, a recombinant replication-incompetent adenovirus serotype 2 expressing codon-optimized Zaire ebolavirus glycoprotein, and evaluated its immunogenicity in mice and rhesus macaques. rAd2-ZGP induced significant antibody and cell-mediated immune responses at 2 weeks after a single immunization...
June 6, 2018: Emerging Microbes & Infections
Alpha K Keita, Christelle Butel, Guillaume Thaurignac, Aminata Diallo, Talla Nioke, Falaye Traoré, Lamine Koivogui, Martine Peeters, Eric Delaporte, Ahidjo Ayouba
Questions remain as whether an unnoticed Ebola outbreak has occurred in Guinea before the 2014-2016 epidemic. To address this, we used a highly sensitive and specific Luminex-based assay for Ebola virus (EBOV) antibody detection to screen blood samples collected in the framework of the Demographic Health Survey performed in 2012 in Guinea. One sample (GF069) of 1,483 tested was positive at very high immunoglobulin G titer to Zaire EBOV in Guinée Forestière. Thus, at least 2 years before the 2014 EVD outbreak in Guinea, Zaire EBOV was circulating in rural areas of this country...
June 4, 2018: American Journal of Tropical Medicine and Hygiene
Kristen E Pascal, Drew Dudgeon, John C Trefry, Manu Anantpadma, Yasuteru Sakurai, Charles D Murin, Hannah L Turner, Jeanette Fairhurst, Marcela Torres, Ashique Rafique, Ying Yan, Ashok Badithe, Kevin Yu, Terra Potocky, Sandra L Bixler, Taylor B Chance, William D Pratt, Franco D Rossi, Joshua D Shamblin, Suzanne E Wollen, Justine M Zelko, Ricardo Carrion, Gabriella Worwa, Hilary M Staples, Darya Burakov, Robert Babb, Gang Chen, Joel Martin, Tammy T Huang, Karl Erlandson, Melissa S Willis, Kimberly Armstrong, Thomas M Dreier, Andrew B Ward, Robert A Davey, Margaret L M Pitt, Leah Lipsich, Peter Mason, William Olson, Neil Stahl, Christos A Kyratsous
Background: For most classes of drugs rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety and PK profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases. Methods: Here we deployed a platform to generate, test and develop fully human antibodies to Zaire ebolavirus...
May 31, 2018: Journal of Infectious Diseases
Michael A Cooper, Bryn O'Meara, Megan M Jack, Dan Elliot, Bradley Lamb, Zair W Khan, Blaise W Menta, Janelle M Ryals, Michelle K Winter, Douglas E Wright
Pain is significantly impacted by the rising epidemic of obesity and metabolic syndrome. Our understanding of how these features impact pain is only beginning to be developed. Here, we investigated how small genetic differences among C57BL/6 mice from two different commercial vendors leads to important differences in the development of high-fat diet-induced mechanical sensitivity. Two sub strains of C57BL/6 mice from Jackson laboratories (C57BL/6J and C57BL/6NIH), as well as C57BL/6 from Charles Rivers (C57BL/6CR) were placed on high-fat diets and analyzed for changes in metabolic features influenced by high-fat diet and obesity, as well as measures of pain related behaviors...
May 24, 2018: Journal of Pain: Official Journal of the American Pain Society
Erik Corona, Liuyang Wang, Dennis Ko, Chirag J Patel
Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens...
2018: PloS One
Michael A Cooper, Blaise W Menta, Consuelo Perez-Sanchez, Megan M Jack, Zair W Khan, Janelle M Ryals, Michelle Winter, Douglas E Wright
Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice...
May 12, 2018: Experimental Neurology
Bing Yang, Alison Schaefer, Ying-Ying Wang, Justin McCallen, Phoebe Lee, Jay M Newby, Harendra Arora, Priya A Kumar, Larry Zeitlin, Kevin J Whaley, Scott A McKinley, William A Fischer, Dimple Harit, Samuel K Lai
Filoviruses, including Ebola, have the potential to be transmitted via virus-laden droplets deposited onto mucus membranes. Protecting against such emerging pathogens will require understanding how they may transmit at mucosal surfaces and developing strategies to reinforce the airway mucus barrier.Here, we prepared Ebola pseudovirus (with Zaire strain glycoproteins) and employed high resolution multiple particle tracking to track the motions of hundreds of individual pseudoviruses in fresh and undiluted human airway mucus isolated from extubated endotracheal tubes...
April 24, 2018: Journal of Infectious Diseases
Ameh S James, Shawn Todd, Nina M Pollak, Glenn A Marsh, Joanne Macdonald
BACKGROUND: The 2014/2015 Ebolavirus outbreak resulted in more than 28,000 cases and 11,323 reported deaths, as of March 2016. Domestic transmission of the Guinea strain associated with the outbreak occurred mainly in six African countries, and international transmission was reported in four countries. Outbreak management was limited by the inability to rapidly diagnose infected cases. A further fifteen countries in Africa are predicted to be at risk of Ebolavirus outbreaks in the future as a consequence of climate change and urbanization...
April 23, 2018: Virology Journal
Angela Huttner, Selidji Todagbe Agnandji, Christophe Combescure, José F Fernandes, Emmanuel Bache Bache, Lumeka Kabwende, Francis Maina Ndungu, Jessica Brosnahan, Thomas P Monath, Barbara Lemaître, Stéphane Grillet, Miriam Botto, Olivier Engler, Jasmine Portmann, Denise Siegrist, Philip Bejon, Peter Silvera, Peter Kremsner, Claire-Anne Siegrist
BACKGROUND: The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. METHODS: In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence...
April 4, 2018: Lancet Infectious Diseases
Haruhiko Fujihira, Katsuaki Usami, Keita Matsuno, Hideyuki Takeuchi, Kaori Denda-Nagai, Jun-Ichi Furukawa, Yasuro Shinohara, Ayato Takada, Yoshihiro Kawaoka, Tatsuro Irimura
Ebolaviruses comprises 5 species that exert varying degrees of mortality/infectivity in humans with Reston ebolaviruses (REBOV) showing the lowest and Zaire ebolaviruses (ZEBOV) showing the highest. However, the molecular basis of this differential mortality/infectivity remains unclear. Here, we report that the structural features of ebolavirus envelope glycoproteins (GPs) and one of their counter receptors, macrophage galactose-type calcium-type lectin (MGL/CD301), play crucial roles in determining viral infectivity...
April 3, 2018: Scientific Reports
Elizabeth Davlantes, Pedro Rafael Dimbu, Carolina Miguel Ferreira, Maria Florinda Joao, Dilunvuidi Pode, Jacinto Félix, Edgar Sanhangala, Benjamin Nieto Andrade, Samaly Dos Santos Souza, Eldin Talundzic, Venkatachalam Udhayakumar, Chantelle Owens, Eliane Mbounga, Lubbe Wiesner, Eric S Halsey, José Franco Martins, Filomeno Fortes, Mateusz M Plucinski
BACKGROUND: The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications' therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces...
April 3, 2018: Malaria Journal
Kendra J Alfson, Anthony Griffiths
Complete inactivation of infectious Ebola virus (EBOV) is required before a sample may be removed from a Biosafety Level 4 laboratory. The United States Federal Select Agent Program regulations require that procedures used to demonstrate chemical inactivation must be validated in-house to confirm complete inactivation. The objective of this study was to develop a method for validating chemical inactivation of EBOV and then demonstrate the effectiveness of several commonly-used inactivation methods. Samples containing infectious EBOV ( Zaire ebolavirus ) in different matrices were treated, and the sample was diluted to limit the cytopathic effect of the inactivant...
March 13, 2018: Viruses
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 nonhuman primates (NHPs) characterized by a high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013 to 2016 outbreak in West Africa highlighted the need for EVD-specific medical countermeasures. Here, we 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)...
June 1, 2018: Journal of Virology
Dragan Ljolje, Pedro Rafael Dimbu, Julia Kelley, Ira Goldman, Douglas Nace, Aleixo Macaia, Eric S Halsey, Pascal Ringwald, Filomeno Fortes, Venkatachalam Udhayakumar, Eldin Talundzic, Naomi W Lucchi, Mateusz M Plucinski
BACKGROUND: Artemisinin-based combination therapy is the first-line anti-malarial treatment for uncomplicated Plasmodium falciparum infection in Angola. To date, the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin resistance, and pfmdr1, associated with lumefantrine resistance, have not been systematically studied in Angola. METHODS: DNA was isolated from pretreatment and late treatment failure dried blood spots collected during the 2015 round of therapeutic efficacy studies in Benguela, Lunda Sul, and Zaire Provinces in Angola...
February 20, 2018: Malaria Journal
Nadege Goumkwa Mafopa, Gianluca Russo, Raoul Emeric Guetiya Wadoum, Emmanuel Iwerima, Vincent Batwala, Marta Giovanetti, Antonella Minutolo, Patrick Turay, Thomas B Turay, Brima Kargbo, Massimo Amicosante, Maurizio Mattei, Carla Montesano
A serosurvey of anti-Ebola Zaire virus nucleoprotein IgG prevalence was carried out among Ebola virus disease survivors and their Community Contacts in Bombali District, Sierra Leone. Our data suggest that the specie of Ebola virus ( Zaire ) responsible of the 2013-2016 epidemic in West Africa may cause mild or asymptomatic infection in a proportion of cases, possibly due to an efficient immune response.
December 31, 2017: Journal of Public Health in Africa
Kristin Post
The unprecedented scale of the Ebola epidemic in West Africa in 2014-15 caught the world by surprise. Zaire Ebolavirus had not previously been documented in Guinea, Sierra Leone, or Liberia. However, since this strain of filovirus was first identified in 1976, scientists have been studying the disease and its origins. They have identified forest-dwelling animals that carry the virus, and some that die from it, but have yet to isolate how it is transmitted from animals to humans. During the height of the Ebola outbreak in West Africa, some public health messages addressed the link among Ebola, wild animals, and humans...
January 2018: Health Security
Wan Ching Lim, Asif M Khan
BACKGROUND: Ebolavirus (EBOV) is responsible for one of the most fatal diseases encountered by mankind. Cellular T-cell responses have been implicated to be important in providing protection against the virus. Antigenic variation can result in viral escape from immune recognition. Mapping targets of immune responses among the sequence of viral proteins is, thus, an important first step towards understanding the immune responses to viral variants and can aid in the identification of vaccine targets...
January 19, 2018: BMC Genomics
Vladimir G Dedkov, N'Faly Magassouba, Marina V Safonova, Sergey A Bodnev, Oleg V Pyankov, Jacob Camara, Bakary Sylla, Alexander P Agafonov, Victor V Maleev, German A Shipulin
Filoviruses are important etiological agents of emergent diseases with high mortality rates. Traditionally, filovirus fever diseases have primarily been a burden of African countries; however, global interconnectedness has increased the probability of the worldwide spread of filoviruses. Therefore, national healthcare organizations need tools for managing filovirus risk, including diagnostic kits based on real-time reverse transcription PCR (RT-qPCR), as this is the most suitable method for diagnosing filovirus fever diseases...
January 2018: Health Security
Shruti Baikerikar
Background: Ebola viral disease is a severe and mostly fatal disease in humans caused by Ebola virus. This virus belongs to family Filoviridae and is a single-stranded negative-sense virus. There is no single treatment for this disease which puts forth the need to identify new therapy to control and treat this fatal condition. Curcumin, one of the bioactives of turmeric, has proven antiviral property. Objective: The current study evaluates the inhibitory activity of curcumin, bisdemethoxycurcumin, demethoxycurcumin, and tetrahydrocurcumin against Zaire Ebola viral proteins (VPs)...
December 2017: Pharmacognosy Research
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