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Ebola vaccine

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https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#1
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
#2
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
https://www.readbyqxmd.com/read/28518027/measles-cases-during-ebola-outbreak-west-africa-2013-2106
#3
Francesca Colavita, Mirella Biava, Concetta Castilletti, Serena Quartu, Francesco Vairo, Claudia Caglioti, Chiara Agrati, Eleonora Lalle, Licia Bordi, Simone Lanini, Michela Delli Guanti, Rossella Miccio, Giuseppe Ippolito, Maria R Capobianchi, Antonino Di Caro
The recent Ebola outbreak in West Africa caused breakdowns in public health systems, which might have caused outbreaks of vaccine-preventable diseases. We tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra Leone, for measles. These patients were negative for Ebola virus. Measles virus IgM was detected in 13 (16%) of the patients.
June 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28516833/animal-models-of-ebolavirus-infection
#4
Marisa C St Claire, Dan R Ragland, Laura Bollinger, Peter B Jahrling
Ebola virus is a highly pathogenic member of the family Filoviridae that causes a severe hemorrhagic disease in humansand NHP. The 2013-2016 West African outbreak has increased interest in the development and refinement of animal models of Ebola virus disease. These models are used to test countermeasures and vaccines, gain scientific insights into the mechanisms of disease progression and transmission, and study key correlates of immunology. Ebola virus is classified as a BSL4 pathogen and Category A agent, for which the United States government requires preparedness in case of bioterrorism...
May 17, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28480779/use-of-human-immunoglobulins-as-an-anti-infective-treatment-the-experience-so-far-and-their-possible-re-emerging-role
#5
Jordi Bozzo, Juan I Jorquera
Pooled human immunoglobulins (IGs) are prepared from plasma obtained from healthy donors as a concentrated antibody-containing solution. In addition, high-titer IGs (hyperimmune) against a specific pathogen can be obtained from vaccinated or convalescing donors. Currently, IGs can be used for the treatment of a variety of infections for which no specific therapy exists or that remain difficult to treat. Moreover, the recent pathogen outbreaks for which there is no approved treatment have renewed attention to the role of convalescent plasma and IGs...
May 15, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28466035/analysis-of-ebola-virus-polymerase-domains-to-find-strain-specific-differences-and-to-gain-insight-on-their-pathogenicity
#6
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/28462833/recent-progress-on-the-treatment-of-ebola-virus-disease-with-favipiravir-and-other-related-strategies
#7
Tao Zhang, Min Zhai, Jianbo Ji, Jian Zhang, Ye Tian, Xinyong Liu
Ebola virus is one of the most threatening pathogens with the mortality rate as high as 90% in the world. There are no licensed therapeutic drugs or preventive vaccines for Ebola hemorrhagic fever up to date. Favipiravir, a novel antiviral drug which was mainly used for the treatment of influenza, now has been demonstrated to have a curative effect in treating Ebola virus infection. In this review, we present an overview of recent progress on the treatment of Ebola virus disease with Favipiravir and describe its possible mechanism...
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28461209/insights-from-clinical-research-completed-during-the-west-africa-ebola-virus-disease-epidemic
#8
REVIEW
Amanda Rojek, Peter Horby, Jake Dunning
The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome...
April 28, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28460340/immunomonitoring-of-human-responses-to-the-rvsv-zebov-ebola-vaccine
#9
REVIEW
Donata Medaglini, Claire-Anne Siegrist
The rVSV-ZEBOV vaccine is currently the only Ebola vaccine with demonstrated clinical efficacy in a ring-vaccination clinical trial. It has been shown to be reactogenic but immunogenic and safe in several Phase I clinical studies. However, its mechanisms of protection are unknown and available immunogenicity data are mostly limited to classical serological analysis; it is now of paramount importance to apply cutting-edge technologies, including transcriptomic and metabolomic analyses, and to perform integrative analyses with standard serology and clinical data to comprehensively profile the rVSV-ZEBOV immune signature...
April 28, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28458053/overexpression-of-ebola-virus-envelope-gp1-protein
#10
Zhongcheng Zou, John Misasi, Nancy Sullivan, Peter D Sun
Ebola virus uses its envelope GP1 and GP2 for viral attachment and entry into host cells. Due to technical difficulty expressing full-length envelope, many structural and functional studies of Ebola envelope protein have been carried out primarily using GP1 lacking its mucin-like domain. As a result, the viral invasion mechanisms involving the mucin-like domain are not fully understood. To elucidate the role of the mucin-like domain of GP1 in Ebola-host attachment and infection and to facilitate vaccine development, we constructed a GP1 expression vector containing the entire attachment region (1-496)...
April 27, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28447193/ebola-and-marburg-virus-vaccines
#11
REVIEW
Pierce Reynolds, Andrea Marzi
The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most pathogenic viruses known to man and the causative agents of viral hemorrhagic fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000 infections were observed in the latest EBOV epidemic in West Africa; previous outbreaks were much smaller, typically only affecting less than a few hundred people. Compared to other diseases such as AIDS or Malaria with millions of cases annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious diseases...
April 26, 2017: Virus Genes
https://www.readbyqxmd.com/read/28446173/impact-of-the-ebola-outbreak-on-routine-immunization-in-western-area-sierra-leone-a-field-survey-from-an-ebola-epidemic-area
#12
Xiaojin Sun, T T Samba, Jianyi Yao, Wenwu Yin, Lin Xiao, Fuqiang Liu, Xiaoqiang Liu, Jikun Zhou, Zengqiang Kou, Hongwei Fan, Hao Zhang, Aqnes Williams, Paul M Lansana, Zundong Yin
BACKGROUND: Since March 2014, the Ebola Virus Disease (EVD) outbreak in West Africa disrupted health care systems - especially in Guinea, Liberia and Sierra Leone - with a consequential stress on the area's routine immunization programs. To address perceived decreased vaccination coverage, Sierra Leone conducted a catch-up vaccination campaign during 24-27 April 2015. We conducted a vaccination coverage survey and report coverage estimates surrounding the time of the EVD outbreak and the catch-up campaign...
April 26, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28434944/dose-dependent-t-cell-dynamics-and-cytokine-cascade-following-rvsv-zebov-immunization
#13
Christine Dahlke, Rahel Kasonta, Sebastian Lunemann, Verena Krähling, Madeleine E Zinser, Nadine Biedenkopf, Sarah K Fehling, My L Ly, Anne Rechtien, Hans C Stubbe, Flaminia Olearo, Saskia Borregaard, Alen Jambrecina, Felix Stahl, Thomas Strecker, Markus Eickmann, Marc Lütgehetmann, Michael Spohn, Stefan Schmiedel, Ansgar W Lohse, Stephan Becker, Marylyn M Addo
BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date...
April 5, 2017: EBioMedicine
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
#14
Matthias J Schnell
No abstract text is available yet for this article.
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28428619/transcriptomic-analysis-reveals-a-previously-unknown-role-for-cd8-t-cells-in-rvsv-ebov-mediated-protection
#15
Andrea R Menicucci, Suhas Sureshchandra, Andrea Marzi, Heinz Feldmann, Ilhem Messaoudi
Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427845/development-of-a-micro-neutralization-assay-for-ebolaviruses-using-a-replication-competent-vesicular-stomatitis-hybrid-virus-and-a-quantitative-pcr-readout
#16
Stella S Lee, Kathryn Phy, Keith Peden, Li Sheng-Fowler
Development of vaccines against highly pathogenic viruses that could also be used as agents of bioterrorism is both a public health issue and a national security priority. Methods that can quantify neutralizing antibodies will likely be crucial in demonstrating vaccine effectiveness, as most licensed viral vaccines are effective due to their capacity to elicit neutralizing antibodies. Assays to determine whether antibodies are neutralizing traditionally involve infectious virus, and the assay most commonly used is the plaque-reduction neutralization test (PRNT)...
April 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28412830/expression-and-immunogenicity-of-vp40-protein-of-zebov
#17
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/28404864/longitudinal-peripheral-blood-transcriptional-analysis-of-a-patient-with-severe-ebola-virus-disease
#18
John C Kash, Kathie-Anne Walters, Jason Kindrachuk, David Baxter, Kelsey Scherler, Krisztina B Janosko, Rick D Adams, Andrew S Herbert, Rebekah M James, Spencer W Stonier, Matthew J Memoli, John M Dye, Richard T Davey, Daniel S Chertow, Jeffery K Taubenberger
The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U...
April 12, 2017: Science Translational 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
#19
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/28402862/cooperativity-enables-non-neutralizing-antibodies-to-neutralize-ebolavirus
#20
Katie A Howell, Jennifer M Brannan, Christopher Bryan, Andrew McNeal, Edgar Davidson, Hannah L Turner, Hong Vu, Sergey Shulenin, Shihua He, Ana Kuehne, Andrew S Herbert, Xiangguo Qiu, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, John M Dye, M Javad Aman
Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several "enabling pairs" of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC50 >1 μM) to exhibit potent neutralization (IC50 1-10 nM)...
April 11, 2017: Cell Reports
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