| recently identified mutations in the ebola virus-makona genome do not alter pathogenicity in animal models. | ebola virus (ebov), isolate makona, the causative agent of the west african ebov epidemic, has been the subject of numerous investigations to determine the genetic diversity and its potential implication for virus biology, pathogenicity, and transmissibility. despite various mutations that have emerged over time through multiple human-to-human transmission chains, their biological relevance remains questionable. recently, mutations in the glycoprotein gp and polymerase l, which emerged and stabi ... | 2018 | 29742435 |
| high dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with ebola virus makona. | the recent epidemic of ebola virus disease in west africa resulted in an unprecedented number of cases and deaths. due to the scope of the outbreak combined with the lack of available approved treatment options, there was strong motivation to investigate any potential drug which had existing data reporting anti-ebola activity. drugs with demonstrated antiviral activity in the nonhuman primate models already approved for another indication or for which there was existing safety data were consider ... | 2017 | 28725019 |
| delayed disease progression in cynomolgus macaques infected with ebola virus makona strain. | in late 2013, the largest documented outbreak of ebola hemorrhagic fever started in guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. in march 2014, ebola virus (ebov) was identified as the causative agent. this study compares the pathogenesis of a new ebov strain, makona, which was isolated in guinea in 2014 with the prototype strain from the 1976 ebov outbreak in the former zaire. both strains cause lethal disease in cynomolgus ... | 2015 | 26402165 |
| broad and temperature independent replication potential of filoviruses on cells derived from old and new world bat species. | filoviruses are strongly associated with several species of bats as their natural reservoirs. in this study, we determined the replication potential of all filovirus species: marburg marburgvirus, taï forest ebolavirus, reston ebolavirus, sudan ebolavirus, zaire ebolavirus, and bundibugyo ebolavirus. filovirus replication was supported by all cell lines derived from 6 old and new world bat species: the hammer-headed fruit bat, buettikofer's epauletted fruit bat, the egyptian fruit bat, the jamai ... | 2016 | 27354372 |
| efficacy of vesicular stomatitis virus-ebola virus postexposure treatment in rhesus macaques infected with ebola virus makona. | the ebola virus (ebov) epidemic in west africa increased the focus on vaccine development against this hemorrhagic fever-causing pathogen, and as a consequence human clinical trials for a few selected platforms were accelerated. one of these vaccines is vesicular stomatitis virus (vsv)-ebov, also known as rvsv-zebov, a fast-acting vaccine against ebov and so far the only vaccine with reported efficacy against ebov infections in humans in phase iii clinical trials. in this study, we analyzed the ... | 2016 | 27496978 |
| passive immunotherapy: assessment of convalescent serum against ebola virus makona infection in nonhuman primates. | convalescent serum and blood were used to treat patients during outbreaks of zaire ebolavirus (zebov) infection in 1976 and 1995, with inconclusive results. during the recent 2013-2016 west african epidemic, serum/plasma from survivors of zebov infection was used to treat patients in the affected countries and several repatriated patients. the effectiveness of this strategy remains unknown. | 2016 | 27571900 |
| lipid nanoparticle sirna treatment of ebola-virus-makona-infected nonhuman primates. | the current outbreak of ebola virus in west africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. several post-exposure interventions have been employed under compassionate use to treat patients repatriated to europe and the united states. however, the in vivo efficacy of these interventions against the new outbreak strain of ebola virus is unknown. here we show that lipid-nanoparticle-encapsulated short interfering rnas (s ... | 2015 | 25901685 |
| human polyclonal antibodies produced by transchromosomal cattle provide partial protection against lethal zaire ebolavirus challenge in rhesus macaques. | antibody therapy has been used to treat a variety of diseases and the success of zmapp and other monoclonal antibody-based therapies during the 2014-2016 west african ebola outbreak has shown this countermeasure can be a successful therapy for ebola hemorrhagic fever. this study utilized transchromosomal bovines (tcb) vaccinated with a dna plasmid encoding ebola virus glycoprotein sequence to produce human polyclonal antibodies directed against ebola virus glycoprotein. when administered 1 day p ... | 2018 | 30053153 |
| fully human immunoglobulin g from transchromosomic bovines treats nonhuman primates infected with ebola virus makona isolate. | transchromosomic bovines (tc-bovines) adaptively produce fully human polyclonal immunoglobulin (ig)g antibodies after exposure to immunogenic antigen(s). the national interagency confederation for biological research and collaborators rapidly produced and then evaluated anti-ebola virus igg immunoglobulins (collectively termed sab-139) purified from tc-bovine plasma after sequential hyperimmunization with an ebola virus makona isolate glycoprotein nanoparticle vaccine. sab-139 was characterized ... | 2018 | 30010950 |
| filoviruses infect rhesus macaque synoviocytes in vivo and primary human synoviocytes in vitro. | the most commonly reported symptom of post-ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent ebola virus infection is not well characterized in human patients or animal models. through immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by ebola virus/kikwit, ebola virus/makona-c05, and marburg virus/angola in the rhesus macaque model. furthermore, histologic analysis, im ... | 2020 | 32479821 |
| comparison of transcriptomic platforms for analysis of whole blood from ebola-infected cynomolgus macaques. | ebola virus disease (evd) is a serious illness with mortality rates of 20-90% in various outbreaks. evd is characterized by robust virus replication and strong host inflammatory response. analyzing host immune responses has increasingly involved multimodal approaches including transcriptomics to profile gene expression. we studied cynomolgus macaques exposed to ebola virus makona via different routes with the intent of comparing rna-seq to a nanostring ncounter codeset targeting 769 non-human pr ... | 2017 | 29116224 |
| transcriptome analysis of circulating immune cell subsets highlight the role of monocytes in zaire ebola virus makona pathogenesis. | existing models of ebola virus disease (evd) suggest antigen-presenting cells are initial targets ofzaire ebolavirus(zebov).in vitrostudies 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 byin vivostudies. in this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, t-cells, and b-cells isolated fr ... | 2017 | 29123522 |