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rapid detection of all known ebolavirus species by reverse transcription-loop-mediated isothermal amplification (rt-lamp).ebola virus disease (evd), a highly virulent infectious disease caused by ebolaviruses, has a fatality rate of 25-90%. without a licensed chemotherapeutic agent or vaccine for the treatment and prevention of evd, control of outbreaks requires accurate and rapid diagnosis of cases. in this study, five sets of six oligonucleotide primers targeting the nucleoprotein gene were designed for specific identification of each of the five ebolavirus species using reverse transcription-loop mediated isothe ...201728356221
antibody treatment of ebola and sudan virus infection via a uniquely exposed epitope within the glycoprotein receptor-binding site.previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (rbs) of ebolavirus glycoproteins have been unsuccessful, largely because the rbs is occluded on the viral surface. we report a monoclonal antibody (fvm04) that targets a uniquely exposed epitope within the rbs; cross-neutralizes ebola (ebov), sudan (sudv), and, to a lesser extent, bundibugyo viruses; and shows protection against ebov and sudv in mice and guinea pigs. the antibody cocktail zmapp™ is remarkabl ...201627160900
comparison of n- and o-linked glycosylation patterns of ebolavirus glycoproteins.ebolaviruses are emerging pathogens that cause severe and often fatal viral hemorrhagic fevers. four distinct ebolaviruses are known to cause ebola virus disease in humans. the ebolavirus envelope glycoprotein (gp1,2) is heavily glycosylated, but the precise glycosylation patterns of ebolaviruses are largely unknown. here we demonstrate that approximately 50 different n-glycan structures are present in gp1,2 derived from the four pathogenic ebolaviruses, including high mannose, hybrid, and bi-, ...201727984785
vp24-karyopherin alpha binding affinities differ between ebolavirus species, influencing interferon inhibition and vp24 stability.zaire ebolavirus (ebov), bundibugyo ebolavirus (bdbv), and reston ebolavirus (restv) belong to the same genus but exhibit different virulence properties. vp24 protein, a structural protein present in all family members, blocks interferon (ifn) signaling and likely contributes to virulence. inhibition of ifn signaling by ebov vp24 (evp24) involves its interaction with the npi-1 subfamily of karyopherin alpha (kpna) nuclear transporters. here, we evaluated evp24, bdbv vp24 (bvp24), and restv vp24 ...201727974555
how severe and prevalent are ebola and marburg viruses? a systematic review and meta-analysis of the case fatality rates and seroprevalence.ebola and marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. the fatality rates reported in different outbreaks ranged from 24-100%. in addition, sero-surveys conducted have shown different seropositivity for both ebola and marburg viruses. we aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countrie ...201627887599
clinical manifestations and case management of ebola haemorrhagic fever caused by a newly identified virus strain, bundibugyo, uganda, 2007-2008.a confirmed ebola haemorrhagic fever (ehf) outbreak in bundibugyo, uganda, november 2007-february 2008, was caused by a putative new species (bundibugyo ebolavirus). it included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (cfr = 25%). study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed ehf patients. clinical findings are congruous with previously reported ehf infections. the most frequently experienced symptoms ...201223285243
vesicular stomatitis virus-based ebola vaccines with improved cross-protective efficacy.for ebola virus (ebov), 4 different species are known: zaire, sudan, côte d'ivoire, and reston ebolavirus. the newly discovered bundibugyo ebolavirus has been proposed as a 5th species. so far, no cross-neutralization among ebov species has been described, aggravating progress toward cross-species protective vaccines. with the use of recombinant vesicular stomatitis virus (rvsv)-based vaccines, guinea pigs could be protected against zaire ebolavirus (zebov) infection only when immunized with a v ...201121987743
filovirus outbreak detection and surveillance: lessons from bundibugyo.the first outbreak of ebola hemorrhagic fever (ehf) due to bundibugyo ebolavirus occurred in uganda from august to december 2007. during outbreak response and assessment, we identified 131 ehf cases (44 suspect, 31 probable, and 56 confirmed). consistent with previous large filovirus outbreaks, a long temporal lag (approximately 3 months) occurred between initial ehf cases and the subsequent identification of ebola virus and outbreak response, which allowed for prolonged person-to-person transmi ...201121987748
single immunization with a monovalent vesicular stomatitis virus-based vaccine protects nonhuman primates against heterologous challenge with bundibugyo ebolavirus.the recombinant vesicular stomatitis virus (rvsv) vector-based monovalent vaccine platform expressing a filovirus glycoprotein has been demonstrated to provide protection from lethal challenge with ebola (ebov) and marburg (marv) viruses both prophylactically and after exposure. this platform provides protection between heterologous strains within a species; however, protection from lethal challenge between species has been largely unsuccessful. to determine whether the rvsv-ebov vaccines have t ...201121987745
serology and cytokine profiles in patients infected with the newly discovered bundibugyo ebolavirus.a new species of ebolavirus, bundibugyo ebolavirus, was discovered in an outbreak in western uganda in november 2007. to study the correlation between fatal infection and immune response in bundibugyo ebolavirus infection, viral antigen, antibodies, and 17 soluble factors important for innate immunity were examined in 44 patient samples. using luminex assays, we found that fatal infection was associated with high levels of viral antigen, low levels of pro-inflammatory cytokines, such as il-1α, i ...201122197674
ebola virus outbreaks in africa: past and present.ebola haemorrhagic fever (ehf) is a zoonosis affecting both human and non-human primates (nhp). outbreaks in africa occur mainly in the congo and nile basins. the first outbreaks of ehf occurred nearly simultaneously in 1976 in the democratic republic of the congo (drc, former zaire) and sudan with very high case fatality rates of 88% and 53%, respectively. the two outbreaks were caused by two distinct species of ebola virus named zaire ebolavirus (zebov) and sudan ebolavirus (sebov). the source ...201223327370
development and evaluation of a panel of filovirus sequence capture probes for pathogen detection by next-generation sequencing.a detailed understanding of the circulating pathogens in a particular geographic location aids in effectively utilizing targeted, rapid diagnostic assays, thus allowing for appropriate therapeutic and containment procedures. this is especially important in regions prevalent for highly pathogenic viruses co-circulating with other endemic pathogens such as the malaria parasite. the importance of biosurveillance is highlighted by the ongoing ebola virus disease outbreak in west africa. for example, ...201425207553
current perspectives on the phylogeny of filoviridae.sporadic fatal outbreaks of disease in humans and non-human primates caused by ebola or marburg viruses have driven research into the characterization of these viruses with the hopes of identifying host tropisms and potential reservoirs. such an understanding of the relatedness of newly discovered filoviruses may help to predict risk factors for outbreaks of hemorrhagic disease in humans and/or non-human primates. recent discoveries such as three distinct genotypes of reston ebolavirus, unexpect ...201121742058
evaluation of realstar reverse transcription-polymerase chain reaction kits for filovirus detection in the laboratory and field.diagnosis of ebola virus (ebov) disease (evd) requires laboratory testing.201627549586
development of a taqman array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including ebola virus.acute febrile illness (afi) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. we developed a real-time pcr-based taqman array card (tac) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 afi-associated organisms, including 15 viruses (chikungunya, crime ...201526491176
isolation and characterisation of ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries.members of the genus ebolavirus cause fulminating outbreaks of disease in human and non-human primate populations with a mortality rate up to 90%. to facilitate rapid detection of these pathogens in clinical and environmental samples, robust reagents capable of providing sensitive and specific detection are required. in this work recombinant antibody libraries were generated from murine (single chain variable domain fragment; scfv) and nurse shark, ginglymostoma cirratum (ignar v) hosts immunise ...201121752470
neglected filoviruses.eight viruses are currently assigned to the family filoviridae marburg virus, sudan virus and, in particular, ebola virus have received the most attention both by researchers and the public from 1967 to 2013. during this period, natural human filovirus disease outbreaks occurred sporadically in equatorial africa and, despite high case-fatality rates, never included more than several dozen to a few hundred infections per outbreak. research emphasis shifted almost exclusively to ebola virus in 201 ...201627268907
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 ...201627354372
ferrets infected with bundibugyo virus or ebola virus recapitulate important aspects of human filovirus disease.bundibugyo virus (bdbv) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. domestic ferrets are commonly used to study other rna viruses, including members of the order mononegavirales to investigate whether ferrets were susceptible to filovirus infections, fe ...201627489269
analytical validation of the reebov antigen rapid test for point-of-care diagnosis of ebola virus infection.ebola virus disease (evd) is a severe viral illness caused by ebola virus (ebov). the 2013-2016 evd outbreak in west africa is the largest recorded, with >11 000 deaths. development of the reebov antigen rapid test (reebov rdt) was expedited to provide a point-of-care test for suspected evd cases.201627587634
ebolavirus {delta}-peptide immunoadhesins inhibit marburgvirus and ebolavirus cell entry.with the exception of reston and lloviu viruses, filoviruses (marburgviruses, ebolaviruses, and "cuevaviruses") cause severe viral hemorrhagic fevers in humans. filoviruses use a class i fusion protein, gp(1,2), to bind to an unknown, but shared, cell surface receptor to initiate virus-cell fusion. in addition to gp(1,2), ebolaviruses and cuevaviruses, but not marburgviruses, express two secreted glycoproteins, soluble gp (sgp) and small soluble gp (ssgp). all three glycoproteins have identical ...201121697477
newly discovered ebola virus associated with hemorrhagic fever outbreak in uganda.over the past 30 years, zaire and sudan ebolaviruses have been responsible for large hemorrhagic fever (hf) outbreaks with case fatalities ranging from 53% to 90%, while a third species, côte d'ivoire ebolavirus, caused a single non-fatal hf case. in november 2007, hf cases were reported in bundibugyo district, western uganda. laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, igm and igg elisa) and a recently developed random-primed pyro ...200819023410
chimeric filoviruses for identification and characterization of monoclonal antibodies.recent experiments suggest that some glycoprotein (gp)-specific monoclonal antibodies (mabs) can protect experimental animals against the filovirus ebola virus (ebov). there is a need for isolation of mabs capable of neutralizing multiple filoviruses. antibody neutralization assays for filoviruses frequently use surrogate systems such as the rhabdovirus vesicular stomatitis indiana virus (vsv), lentiviruses or gammaretroviruses with their envelope proteins replaced with ebov gp or pseudotyped wi ...201626819310
cross-reactive and potent neutralizing antibody responses in human survivors of natural ebolavirus infection.recent studies have suggested that antibody-mediated protection against the ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse ebolavirus species, such as ebola virus (ebov), sudan virus (sudv), and bundibugyo virus (bdbv). we isolated a large panel of human monoclonal antibodies (mabs) against bdbv glycoprotein (gp) using peripheral blood b cells from survivors of the 2007 bdbv outbreak in ...201626806128
ebola virus disease in pregnancy: clinical, histopathologic, and immunohistochemical findings.here we describe clinicopathologic features of ebola virus disease in pregnancy. one woman infected with sudan virus in gulu, uganda, in 2000 had a stillbirth and survived, and another woman infected with bundibugyo virus had a live birth with maternal and infant death in isiro, the democratic republic of the congo in 2012. ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental st ...201727226206
discovery of an antibody for pan-ebolavirus therapy.during the latest outbreak of ebola virus disease in west africa, monoclonal antibody therapy (e.g., zmapp) was utilized to treat patients. however, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species zaire ebolavirus. although this particular species has indeed caused the majority of human infections in central and, recently, west africa, other ebolavirus species (e.g., sudan ebolavir ...201626861827
serological evidence of ebola virus infection in indonesian orangutans.ebola virus (ebov) and marburg virus (marv) belong to the family filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. despite the discovery of ebov (reston virus) in nonhuman primates and domestic pigs in the philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in asia is lacking. in this study, serum samples collected from 353 healthy bornean orangutans (pongo ...201222815803
structural basis for differential neutralization of ebolaviruses.there are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (ebola virus, sudan virus, reston virus, taï forest virus, and bundibugyo virus). the small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed gp₁,₂. curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in v ...201222590681
ebolavirus replication and tetherin/bst-2.ebolavirus (ebov) is an enveloped, non-segmented, negative-stranded rna virus, which consists of five species: zaire ebolavirus, sudan ebolavirus, tai forest ebolavirus, bundibugyo ebolavirus, and reston ebolavirus. ebov causes a lethal hemorrhagic fever in both humans and non-human primates. the ebov rna genome encodes seven viral proteins: np, vp35, vp40, gp, vp30, vp24, and l. vp40 is a matrix protein and is essential for virus assembly and release from host cells. expression of vp40 in mamma ...201222485110
vaccines against 'the other' ebolavirus species.the ebolavirus genus includes five member species, all of which pose a threat to global public health. these viruses cause fatal hemorrhagic fever in humans and nonhuman primates, and are considered category a pathogens due to the risk of their use as a bioweapon. the potential for an outbreak, either as a result of a natural emergence, deliberate release, or imported case underscores the need for protective vaccines. recent progress in advancing vaccines for use against the strain of zaire ebol ...201627010528
vesicular stomatitis virus-based vaccines protect nonhuman primates against bundibugyo ebolavirus.ebola virus (ebov) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). currently, there are no licensed vaccines or therapeutics for human use. recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode an ebov glycoprotein in place of the vsv glycoprotein, have shown 100% efficacy against homologous sudan ebolavirus (sebov) or zaire ebolavirus (zebov) challenge in nhps. in addition, a single injection of a blend of three rvsv vectors co ...201324367715
spontaneous mutation at amino acid 544 of the ebola virus glycoprotein potentiates virus entry and selection in tissue culture.ebolaviruses have a surface glycoprotein (gp1,2) that is required for virus attachment and entry into cells. mutations affecting gp1,2 functions can alter virus growth properties. we generated a recombinant vesicular stomatitis virus encoding ebola virus makona variant gp1,2 (rvsv-mak-gp) and observed emergence of a t544i mutation in the makona gp1,2 gene during tissue culture passage in certain cell lines. the t544i mutation emerged within two passages when vsv-mak-gp was grown on vero e6, vero ...201728539437
a systematic review and meta-analysis of seroprevalence surveys of ebolavirus infection.asymptomatic ebolavirus infection could greatly influence transmission dynamics, but there is little consensus on how frequently it occurs or even if it exists. this paper summarises the available evidence on seroprevalence of ebola, sudan and bundibugyo virus igg in people without known ebolavirus disease. through systematic review, we identified 51 studies with seroprevalence results in sera collected from 1961 to 2016. we tabulated findings by study population, contact, assay, antigen and pos ...201728140390
genomic analysis of filoviruses associated with four viral hemorrhagic fever outbreaks in uganda and the democratic republic of the congo in 2012.in 2012, an unprecedented number of four distinct, partially overlapping filovirus-associated viral hemorrhagic fever outbreaks were detected in equatorial africa. analysis of complete virus genome sequences confirmed the reemergence of sudan virus and marburg virus in uganda, and the first emergence of bundibugyo virus in the democratic republic of the congo.201323711383
mapping of conserved and species-specific antibody epitopes on the ebola virus nucleoprotein.filoviruses (viruses in the genus ebolavirus and marburgvirus in the family filoviridae) cause severe haemorrhagic fever in humans and nonhuman primates. rapid, highly sensitive, and reliable filovirus-specific assays are required for diagnostics and outbreak control. characterisation of antigenic sites in viral proteins can aid in the development of viral antigen detection assays such immunochromatography-based rapid diagnosis. we generated a panel of mouse monoclonal antibodies (mabs) to the n ...201323702199
guide to the correct use of filoviral nomenclature.the international committee on taxonomy of viruses (ictv) currently recognizes three genera and seven species as part of the mononegaviral family filoviridae. eight distinct filoviruses (bundibugyo virus, ebola virus, lloviu virus, marburg virus, ravn virus, reston virus, sudan virus, and taï forest virus) have been assigned to these seven species. this chapter briefly summarizes the status quo of filovirus classification and focuses on the importance of differentiating between filoviral species ...201728653188
nonhuman primate models of ebola virus disease.ebola virus disease (evd) in humans is associated with four ebolaviruses: ebola virus (ebov), sudan virus (sudv), bundibugyo virus (bdbv), and taï forest virus. to date, no documented cases of human disease have been associated with reston virus. here, we describe the nonhuman primate (nhp) models that currently serve as gold standards for testing ebolavirus vaccines and therapeutic agents and elucidating underlying mechanisms of pathogenesis. although multiple models have been explored over the ...201728643203
facile discovery of a diverse panel of anti-ebola virus antibodies by immune repertoire mining.the ongoing evolution of ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. there is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different ebolaviruses. we developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the vh:vl paired antibody repertoire encoded by highly expanded b ...201526355042
filovirus virulence in interferon α/β and γ double knockout mice, and treatment with favipiravir.the 2014 ebolavirus outbreak in west africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. a well-characterized small animal model that is susceptible to wild-type filoviruses would facilitate the screening of anti-filovirus agents. to that end, we characterized knockout mice lacking α/β and γ interferon receptors (ifnagr ko) as a model for wild-type filovirus infection. intraperitoneal challenge of ifnagr ko mice with several known human pathogenic ...201930717492
macaque monoclonal antibodies targeting novel conserved epitopes within filovirus glycoprotein.filoviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. current immunotherapeutic options for filoviruses are mostly specific to ebola virus (ebov), although other members of filoviridae such as sudan virus (sudv), bundibugyo virus (bdbv), and marburg virus (marv) have also caused sizeable human outbreaks. here we report a set of pan-ebolavirus and pan-filovirus monoclonal antibodies (mabs) derived from cynomolgus macaques immunized repeatedly with a mixture of e ...201526468532
ebola virus disease: an emerging and re-emerging viral threat.the genus ebolavirus from the family filoviridae is composed of five species including sudan ebolavirus, reston ebolavirus, bundibugyo ebolavirus, taï forest ebolavirus, and ebola virus (previously known as zaire ebolavirus). these viruses have a large non-segmented, negative-strand rna of approximately 19 kb that encodes for glycoproteins (i.e., gp, sgp, ssgp), nucleoproteins, virion proteins (i.e., vp 24, 30,40) and an rna dependent rna polymerase. these viruses have become a global health con ...202031806422
magnus representation of genome sequences.we introduce an alignment-free method, the magnus representation, to analyze genome sequences. the magnus representation captures higher-order information in genome sequences. we combine our approach with the idea of k-mers to define an effectively computable mean magnus vector. we perform phylogenetic analysis on three datasets: mosquito-borne viruses, filoviruses, and bacterial genomes. our results on ebolaviruses are consistent with previous phylogenetic analyses, and confirm the modern viewp ...201931398316
ebola virus disease outbreak in isiro, democratic republic of the congo, 2012: signs and symptoms, management and outcomes.data collected during the 2012 ebola virus disease (evd) epidemic in the democratic republic of the congo were analysed for clinical signs, symptoms and case fatality of evd caused by bundibugyo virus (bdbv), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. in a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the eb ...201526107529
bundibugyo ebolavirus survival is associated with early activation of adaptive immunity and reduced myeloid-derived suppressor cell signaling.ebolaviruses bundibugyo virus (bdbv) and ebola virus (ebov) cause fatal hemorrhagic disease in humans and nonhuman primates. while the host response to ebov is well characterized, less is known about bdbv infection. moreover, immune signatures that mediate natural protection against all ebolaviruses remain poorly defined. to explore these knowledge gaps, we transcriptionally profiled bdbv-infected rhesus macaques, a disease model that results in incomplete lethality. this approach enabled us to ...202134372693
the ferret as a model for filovirus pathogenesis and countermeasure evaluation.the domestic ferret (mustela putorius furo) has long been a popular animal model for evaluating viral pathogenesis and transmission as well as the efficacy of candidate countermeasures. without question, the ferret has been most widely implemented for modeling respiratory viruses, particularly influenza viruses; however, in recent years, it has gained attention as a novel animal model for characterizing filovirus infections. although ferrets appear resistant to infection and disease caused by ma ...202133951727
interferon α/β receptor-deficient mice as a model for ebola virus disease.a major obstacle in ebolavirus research is the lack of a small-animal model for sudan virus (sudv), as well as other wild-type (wt) ebolaviruses. here, we expand on research by bray and by lever et al suggesting that wt ebolaviruses are pathogenic in mice deficient for the type 1 interferon (ifn) α/β receptor (ifnα/βr-/-). we examined the disease course of several wt ebolaviruses: boneface (sudv/bon) and gulu variants of sudv, ebola virus (ebov), bundibugyo virus (bdbv), taï forest virus, and re ...201525943199
proposal for a revised taxonomy of the family filoviridae: classification, names of taxa and viruses, and virus abbreviations.the taxonomy of the family filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. the current taxonomy has only been partially accepted by most laboratory virologists. confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the simila ...201021046175
ebola hemorrhagic fever associated with novel virus strain, uganda, 2007-2008.during august 2007-february 2008, the novel bundibugyo ebolavirus species was identified during an outbreak of ebola viral hemorrhagic fever in bundibugyo district, western uganda. to characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. we identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. laboratory confirmation lagged behind outbreak verifi ...201020587179
reduced virus replication, proinflammatory cytokine production, and delayed macrophage cell death in human pbmcs infected with the newly discovered bundibugyo ebolavirus relative to zaire ebolavirus.bundibugyo ebolavirus is a newly identified ebolavirus species. the virus was responsible for a recent hemorrhagic fever outbreak in uganda with an approximate 30% case fatality rate. in this study, we compared the pathogenesis of bundibugyo with highly lethal zaire ebolavirus by using in vitro human pbmcs. we found that pbmcs infected with bundibugyo ebolaviruses resulted in 1 to 2 log lower virus yields compared to zaire ebolavirus and produced 2- to 10-fold lower levels of tnf-alpha, mcp-1, i ...201020394957
development of a human antibody cocktail that deploys multiple functions to confer pan-ebolavirus protection.passive administration of monoclonal antibodies (mabs) is a promising therapeutic approach for ebola virus disease (evd). however, all mabs and mab cocktails that have entered clinical development are specific for a single member of the ebolavirus genus, ebola virus (ebov), and ineffective against outbreak-causing bundibugyo virus (bdbv) and sudan virus (sudv). here, we advance mbp134, a cocktail of two broadly neutralizing human mabs, adi-15878 from an evd survivor and adi-23774 from the same s ...201930629917
ebolavirus chimerization for the development of a mouse model for screening of bundibugyo-specific antibodies.screening of monoclonal antibodies against ebolaviruses requires small-animal models. wild-type mice require adaptation of ebolaviruses, whereas immunodeficient mice are still resistant to nonadapted bundibugyo ebolavirus. swapping of ebola virus glycoprotein with that from bundibugyo virus resulted in a replication-competent chimeric virus, which caused 100% lethal infection in stat1 knockout mice. monoclonal antibody bdbv223 isolated from a human survivor of bundibugyo virus infection protecte ...201830060231
a bivalent, spherical virus-like particle vaccine enhances breadth of immune responses against pathogenic ebola viruses in rhesus macaques.the 2013-2016 ebola outbreak in west africa led to accelerated efforts to develop vaccines against these highly virulent viruses. a live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly effective. vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia ankara (mva) ebola vaccine also appear promising and are progressing in clinical evaluation. however, the ability ...202032075939
efficacy of human monoclonal antibody monotherapy against bundibugyo virus infection in nonhuman primates.the 2013-2016 ebola virus disease (evd) epidemics in west africa highlighted a need for effective therapeutics for treatment of the disease caused by filoviruses. monoclonal antibodies (mabs) are promising therapeutic candidates for prophylaxis or treatment of virus infections. data about efficacy of human mab monotherapy against filovirus infections in preclinical nonhuman primate models are limited.201829982718
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