| pathogenesis of filoviral haemorrhagic fevers. | the filoviruses, marburgvirus and ebolavirus, cause epidemics of haemorrhagic fever with high case-fatality rates. the severe illness results from a complex of pathogenetic mechanisms that enable the virus to suppress innate and adaptive immune responses, infect and kill a broad variety of cell types, and elicit strong inflammatory responses and disseminated intravascular coagulation, producing a syndrome resembling septic shock. most experimental data have been obtained on zaire ebolavirus, whi ... | 2004 | 15288821 |
| development of a cadvax-based bivalent ebola virus vaccine that induces immune responses against both the sudan and zaire species of ebola virus. | ebola virus (ebov) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. while lethal human outbreaks have so far been restricted to sub-saharan africa, the potential exploitation of ebov as a biological weapon cannot be ignored. two species of ebov, sudan ebolavirus (sebov) and zaire ebolavirus (zebov), have been responsible for all of the deadly human outbreaks resulting from this virus. therefore, it is important to develop a vaccine that can pre ... | 2006 | 16501083 |
| the signal peptide of the ebolavirus glycoprotein influences interaction with the cellular lectins dc-sign and dc-signr. | the c-type lectins dc-sign and dc-signr (collectively referred to as dc-sign/r) bind to the ebolavirus glycoprotein (ebov-gp) and augment viral infectivity. dc-sign/r strongly enhance infection driven by the gp of ebov subspecies. zaire (zebov) but have a much less pronounced effect on infection mediated by the gp of ebov subspecies. sudan (sebov). for this study, we analyzed the determinants of the differential dc-sign/r interactions with zebov- and sebov-gp. the efficiency of dc-sign engagemen ... | 2006 | 16775318 |
| recombinant vesicular stomatitis virus vector mediates postexposure protection against sudan ebola hemorrhagic fever in nonhuman primates. | recombinant vesicular stomatitis virus (vsv) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against marburg virus when administered after exposure and can partially protect macaques after challenge with zaire ebolavirus. here, we administered a vsv vector expressing the sudan ebolavirus (sebov) glycoprotein to four rhesus macaques shortly after exposure to sebov. all four animals survived sebov challenge, while a control animal that received a nonspec ... | 2008 | 18385248 |
| single-injection vaccine protects nonhuman primates against infection with marburg virus and three species of ebola virus. | the filoviruses marburg virus and ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (vsv) that expresses a single filovirus glycoprotein (gp) in place of the vsv glycoprotein (g). here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman pr ... | 2009 | 19386702 |
| protection of nonhuman primates against two species of ebola virus infection with a single complex adenovirus vector. | ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. to meet the need for a vaccine against the several types of ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (ebo7) that expresses the glycoproteins of zaire ebolavirus (zebov) and sudan ebolavirus (sebov) in a single complex adenovirus-based vector (cadvax). we evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes ... | 2010 | 20181765 |
| antiviral activity of a small-molecule inhibitor of filovirus infection. | there exists an urgent need to develop licensed drugs and vaccines for the treatment or prevention of filovirus infections. fgi-103 is a low-molecular-weight compound that was discovered through an in vitro screening assay utilizing a variant of zaire ebolavirus (zebov) that expresses green fluorescent protein. in vitro analyses demonstrated that fgi-103 also exhibits antiviral activity against wild-type zebov and sudan ebolavirus, as well as marburgvirus (marv) strains ci67 and ravn. in vivo ad ... | 2010 | 20211898 |
| a replication defective recombinant ad5 vaccine expressing ebola virus gp is safe and immunogenic in healthy adults. | ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial africa. case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. studies of ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous phase i clinical trial of a 1st generation ebola dna vaccine. we now report the safety and immunog ... | 2010 | 21034824 |
| 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 ... | 2010 | 21046175 |
| 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 ... | 2011 | 21987743 |
| generation and epitope mapping of a monoclonal antibody against nucleoprotein of ebola virus. | ebola virus (ebov) causes highly lethal hemorrhagic fever in humans and nonhuman primates and has a significant impact on public health. the nucleoprotein (np) of ebov (ebov-np) plays a central role in virus replication and has been used as a target molecule for disease diagnosis. in this study, we generated a monoclonal antibody (mab) against ebov-np and mapped the epitope motif required for recognition by the mab. the mab generated via immunization of mice with prokaryotically expressed recomb ... | 2012 | 23457784 |
| development and characterization of a guinea pig-adapted sudan virus. | infections with sudan virus (sudv), a member of the genus ebolavirus, result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. the paucity of prophylactics and therapeutics against sudv is attributed to the lack of a small-animal model to screen promising compounds. by repeatedly passaging sudv within the livers and spleens of guinea pigs in vivo, a guinea pig-adapted sudv variant (sudv-ga) uniformly lethal to these animals, with a 50% lethal dose (ld50) of 5.3 × 10( ... | 2015 | 26491156 |
| venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus. | there are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. previously, a replicon vaccine based on venezuelan equine encephalitis virus (veev) demonstrated protective efficacy against marburg virus in nonhuman primates. here, we report the protective efficacy of sudan virus (sudv)- and ebola virus (ebov)-specific veev replicon particle (vrp) vaccines in nonhuman primates. vrp vaccines were developed to express the glycoprotein (gp) of either ... | 2013 | 23408633 |
| 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 ... | 2016 | 27160900 |
| 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 ... | 2017 | 28356221 |
| 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 |
| 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 |
| geographic potential of disease caused by ebola and marburg viruses in africa. | filoviruses represent a significant public health threat worldwide. west africa recently experienced the largest-scale and most complex filovirus outbreak yet known, which underlines the need for a predictive understanding of the geographic distribution and potential for transmission to humans of these viruses. here, we used ecological niche modeling techniques to understand the relationship between known filovirus occurrences and environmental characteristics. our study derived a picture of the ... | 2016 | 27311387 |
| 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 ... | 2016 | 26806128 |
| a single-vector, single-injection trivalent filovirus vaccine: proof of concept study in outbred guinea pigs. | the filoviruses, marburg marburgvirus (marv), zaire ebolavirus (zebov), and sudan ebolavirus (sebov), cause severe and often fatal hemorrhagic fever in humans and nonhuman primates (nhps). monovalent recombinant vesicular stomatitis virus (rvsv)-based vaccine vectors, which encode a filovirus glycoprotein (gp) in place of the vsv glycoprotein, have shown 100% efficacy against homologous filovirus challenge in rodent and nhp studies. here, we examined the utility of a single-vector, single-inject ... | 2015 | 25957964 |
| 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. | 2016 | 27587634 |
| homologous and heterologous protection of nonhuman primates by ebola and sudan virus-like particles. | filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (vlps) have shown efficacy in nonhuman primates. previous studies have shown protection of cynomolgus macaques against homologous infection for ebola virus (ebov) and marburg virus (marv) following a three-dose vaccine regimen of ebov or marv vlps, as well as heterologous protection against ravn virus (r ... | 2015 | 25793502 |
| development of a sensitive and specific serological assay based on luminex technology for detection of antibodies to zaire ebola virus. | the recent zaire ebola virus (ebov) outbreak in west africa illustrates clearly the need for additional studies with humans and animals to elucidate the ecology of ebola viruses (ebvs). in this study, we developed a serological assay based on the luminex technology. nine recombinant proteins representing different viral regions (nucleoprotein [np], 40-kda viral protein [vp40], and glycoprotein [gp]) from four of the five ebv lineages were used. samples from 94 survivors of the ebov outbreak in g ... | 2017 | 27795350 |
| novel activities by ebolavirus and marburgvirus interferon antagonists revealed using a standardized in vitro reporter system. | filoviruses are highly lethal in humans and nonhuman primates, likely due to potent antagonism of host interferon (ifn) responses early in infection. filoviral protein vp35 is implicated as the major ifn induction antagonist, while ebola virus (ebov) vp24 or marburg virus (marv) vp40 are known to block downstream ifn signaling. despite progress elucidating ebov and marv antagonist function, those for most other filoviruses, including reston (restv), sudan (sudv), taï forest (tafv), bundibugyo (b ... | 2017 | 27930961 |
| 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 ... | 2013 | 24367715 |
| 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 ... | 2012 | 23327370 |
| Lethality and pathogenesis of airborne infection with filoviruses in A129 a/ß -/- interferon receptor-deficient mice. | Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 a/ß -/- interferon receptor-deficient KO mice, strain ... | 2012 | 21852521 |
| filovirus infection of stat-1 knockout mice. | we evaluated the susceptibility to ebola and marburg virus infection of mice that cannot respond to interferon (ifn)-α/β and ifn-γ because of deletion of the stat-1 gene. a mouse-adapted zaire ebolavirus (zebov) caused rapidly lethal disease; wild-type zebov and sudan ebolavirus and 4 different marburg virus strains produced severe, but more slowly progressive illness; and reston ebolavirus caused mild disease that was late in onset. the virulence of each agent was mirrored by the pace and sever ... | 2011 | 21987780 |
| 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 ... | 2012 | 22485110 |
| [vesicular stomatitis virus (vsv) as a vaccine vector for immunization against viral infections]. | vesicular stomatitis virus (vsv), a member of the rhabdoviridae family, is a promising candidate for potential use in construction of antiviral vaccines. in the natural environment vsv is a pathogen of wild ungulates and livestock. some of the features that make vsv an excellent platform for the development of a range of viral therapeutics includes its immunogenicity and ability to grow to high titers in cell lines approved for vaccine use. infection in humans is rare and usually asymptomatic, w ... | 2013 | 24379275 |
| 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 ... | 2011 | 21752470 |
| blood chemistry measurements and d-dimer levels associated with fatal and nonfatal outcomes in humans infected with sudan ebola virus. | blood samples from patients infected with the sudan species of ebola virus (ebov), obtained during an outbreak of disease in uganda in 2000, were tested for a panel of analytes to evaluate their clinical condition and to compare values obtained for patients with fatal and nonfatal cases and for uninfected (hospitalized control) patients. liver function tests showed higher levels of aspartate aminotransferase (ast) in blood samples from patients with fatal cases than in samples from patients with ... | 2007 | 17940972 |
| induction of broad cytotoxic t cells by protective dna vaccination against marburg and ebola. | marburg and ebola hemorrhagic fevers have been described as the most virulent viral diseases known to man due to associative lethality rates of up to 90%. death can occur within days to weeks of exposure and there is currently no licensed vaccine or therapeutic. recent evidence suggests an important role for antiviral t cells in conferring protection, but little detailed analysis of this response as driven by a protective vaccine has been reported. we developed a synthetic polyvalent-filovirus d ... | 2013 | 23670573 |
| molecular evolution of viruses of the family filoviridae based on 97 whole-genome sequences. | viruses in the ebolavirus and marburgvirus genera (family filoviridae) have been associated with large outbreaks of hemorrhagic fever in human and nonhuman primates. the first documented cases occurred in primates over 45 years ago, but the amount of virus genetic diversity detected within bat populations, which have recently been identified as potential reservoir hosts, suggests that the filoviruses are much older. here, detailed bayesian coalescent phylogenetic analyses are performed on 97 who ... | 2013 | 23255795 |
| rescue of non-human primates from advanced sudan ebolavirus infection with lipid encapsulated sirna. | although significant progress has been made in developing therapeutics against zaire ebolavirus, these therapies do not protect against other ebola species such as sudan ebolavirus (sudv). here, we describe an rna interference therapeutic comprising sirna targeting the sudv vp35 gene encapsulated in lipid nanoparticle (lnp) technology with increased potency beyond formulations used in tkm-ebola clinical trials. twenty-five rhesus monkeys were challenged with a lethal dose of sudv. twenty animals ... | 2016 | 27670117 |
| cytokine and chemokine expression in humans infected with sudan ebola virus. | the size and duration of the 2000 outbreak of sudan ebola virus (sebov) infection in uganda made it possible to collect serial serum samples from 87 patients (53 survivors and 34 nonsurvivors). surprisingly, the levels of tumor necrosis factor- alpha and interferon (ifn)- gamma , which had been found to be increased in patients with fatal zaire ebola virus infection, were not increased in any of the patients with sebov infection. the levels of interleukin (il)-1 beta , ifn- gamma -inducible prot ... | 2007 | 17940971 |
| sequence-based human leukocyte antigen-b typing of patients infected with ebola virus in uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes. | the sudan species of ebola virus (sebov) causes severe, often fatal infection in approximately 50% of infected humans. we sought to determine whether the human leukocyte antigen-b (hla-b) locus has a role in the outcome of sebov disease by typing 77 cases from an outbreak in northern uganda in 2000-2001. sequence-based hla-b typing was performed using leukocytes isolated from 77 patients. statistical analysis and a predictive discriminant analysis (pda) were applied to typing data. epitope predi ... | 2007 | 17940968 |
| diagnostic reverse-transcription polymerase chain reaction kit for filoviruses based on the strain collections of all european biosafety level 4 laboratories. | a network of european biosafety level 4 laboratories has designed the first industry-standard molecular assay for all filoviruses species, based on the strain collections of all participants. it uses 5 optimized l gene primers and 3 probes, as well as an internal control with a separate detection probe. detection limits (probit analysis, 95% detection chance) were as follows: zaire ebolavirus, 487 copies/ml of plasma; sudan ebolavirus maleo, 586 copies/ml; sudan ebolavirus gulu, 1128 copies/ml; ... | 2007 | 17940950 |
| a characterization of aerosolized sudan virus infection in african green monkeys, cynomolgus macaques, and rhesus macaques. | filoviruses are members of the genera ebolavirus, marburgvirus, and "cuevavirus". because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as cdc category a bioterrorism agents. filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. this study explores the characteristics of aerosolized sudan virus (sudv) boniface in non-h ... | 2012 | 23202456 |
| profiling the native specific human humoral immune response to sudan ebola virus strain gulu by chemiluminescence enzyme-linked immunosorbent assay. | ebolavirus, a member of the family filoviridae, causes high lethality in humans and nonhuman primates. research focused on protection and therapy for ebola virus infection has investigated the potential role of antibodies. recent evidence suggests that antibodies can be effective in protection from lethal challenge with ebola virus in nonhuman primates. however, despite these encouraging results, studies have not yet determined the optimal antibodies and composition of an antibody cocktail, if r ... | 2012 | 22993411 |
| reemerging sudan ebola virus disease in uganda, 2011. | two large outbreaks of ebola hemorrhagic fever occurred in uganda in 2000 and 2007. in may 2011, we identified a single case of sudan ebola virus disease in luwero district. the establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities. | 2012 | 22931687 |
| 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 ... | 2017 | 28539437 |
| current knowledge on lower virulence of reston ebola virus (in french: connaissances actuelles sur la moindre virulence du virus ebola reston). | ebola viruses (ebov) and marburg virus belong to the family filoviridae, order mononegavirales. the genus ebolavirus consists of four species: zaire ebolavirus (zebov), sudan ebolavirus (sebov), ivory coast ebolavirus (icebov) and reston ebolavirus (rebov). three species of ebolaviruses, zebov, sebov, icebov, and marburg virus are known to be extremely pathogenic in primates and humans and cause severe hemorrhagic fever leading up to case fatality rate of some 90%, while rebov is thought to be p ... | 2007 | 17610952 |
| characterization of sudan ebolavirus infection in ferrets. | sudan virus (sudv) outbreaks in africa are highly lethal; however, the development and testing of novel antivirals and vaccines for this virus has been limited by a lack of suitable animal models. non-human primates (nhp) remain the gold standard for modeling filovirus disease, but they are not conducive to screening large numbers of experimental compounds and should only be used to test the most promising candidates. therefore, other smaller animal models are a valuable asset. we have recently ... | 2017 | 28545034 |
| rapid diagnosis of ebola hemorrhagic fever by reverse transcription-pcr in an outbreak setting and assessment of patient viral load as a predictor of outcome. | the largest outbreak on record of ebola hemorrhagic fever (ehf) occurred in uganda from august 2000 to january 2001. the outbreak was centered in the gulu district of northern uganda, with secondary transmission to other districts. after the initial diagnosis of sudan ebolavirus by the national institute for virology in johannesburg, south africa, a temporary diagnostic laboratory was established within the gulu district at st. mary's lacor hospital. the laboratory used antigen capture and rever ... | 2004 | 15047846 |
| genetic changes at the glycoprotein editing site associated with serial passage of sudan virus. | sudan virus (sudv), like the closely related ebola virus (ebov), is a filovirus that causes severe hemorrhagic disease. they both contain an rna editing site in the glycoprotein gene that controls expression of soluble and full-length protein. we tested the consequences of cell culture passage on the genome sequence at the sudv editing site locus and determined whether this affected virulence. passage resulted in expansion of the sudv editing site, similar to that observed with ebov. we compared ... | 2015 | 25920319 |
| amiodarone and metabolite mdea inhibit ebola virus infection by interfering with the viral entry process. | ebola virus disease (evd) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. in the present work, we investigated how amiodarone interferes with ebola virus infection. wild-type sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the zaire ebolavirus glycoprot ... | 2015 | 25933611 |
| 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 ... | 2020 | 32075939 |
| an adenovirus serotype 2-vectored ebolavirus vaccine generates robust antibody and cell-mediated immune responses in mice and rhesus macaques. | 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 ... | 2018 | 29872043 |
| 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 ... | 2015 | 25943199 |
| high-resolution crystal structure of dimeric vp40 from sudan ebolavirus. | ebolaviruses cause severe hemorrhagic fever. central to the ebola life cycle is the matrix protein vp40, which oligomerizes and drives viral budding. here we present the crystal structure of the sudan virus (sudv) matrix protein. this structure is higher resolution (1.6 å) than previously achievable. despite differences in the protein purification, we find that it still forms a stable dimer in solution, as was noted for other ebola vp40s. although the n-terminal domain interface by which vp40 di ... | 2015 | 25957961 |
| preclinical development of inactivated rabies virus-based polyvalent vaccine against rabies and filoviruses. | we previously described the generation of a novel ebola virus (ebov) vaccine based on inactivated rabies virus (rabv) containing ebov glycoprotein (gp) incorporated in the rabv virion. our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (nhps). protection against viral challenge depended largely on the quality of the humoral immune response against ebov gp.here we present the extension and improvement of this vaccine by increasing the amount of ... | 2015 | 26063224 |
| a multi-filovirus vaccine candidate: co-expression of ebola, sudan, and marburg antigens in a single vector. | in the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. this is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. this is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhag ... | 2020 | 32455764 |
| 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 ... | 2020 | 31806422 |
| evaluation of signature erosion in ebola virus due to genomic drift and its impact on the performance of diagnostic assays. | genome sequence analyses of the 2014 ebola virus (ebov) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. we evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. we further empirically evaluated many ebov assays, under real time pcr conditions using ... | 2015 | 26090727 |
| human polyclonal antibodies produced through dna vaccination of transchromosomal cattle provide mice with post-exposure protection against lethal zaire and sudan ebolaviruses. | dna vaccination of transchromosomal bovines (tcbs) with dna vaccines expressing the codon-optimized (co) glycoprotein (gp) genes of ebola virus (ebov) and sudan virus (sudv) produce fully human polyclonal antibodies (pabs) that recognize both viruses and demonstrate robust neutralizing activity. each tcb was vaccinated by intramuscular electroporation (im-ep) a total of four times and at each administration received 10 mg of the ebov-gpco dna vaccine and 10 mg of the sudv-gpco dna vaccine at two ... | 2015 | 26422247 |
| 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 ... | 2015 | 26468532 |
| 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 ... | 2016 | 26861827 |
| molecular architecture of the nucleoprotein c-terminal domain from the ebola and marburg viruses. | the filoviridae family of negative-sense, single-stranded rna (ssrna) viruses is comprised of two species of marburgvirus (marv and ravv) and five species of ebolavirus, i.e. zaire (ebov), reston (restv), sudan (sudv), taï forest (tafv) and bundibugyo (bdbv). in each of these viruses the ssrna encodes seven distinct proteins. one of them, the nucleoprotein (np), is the most abundant viral protein in the infected cell and within the viral nucleocapsid. it is tightly associated with the viral rna ... | 2016 | 26894534 |
| 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 ... | 2016 | 27010528 |
| development, evaluation, and integration of a quantitative reverse-transcription polymerase chain reaction diagnostic test for ebola virus on a molecular diagnostics platform. | the 2013-2016 ebola epidemic in west africa resulted in accelerated development of rapid diagnostic tests for emergency outbreak preparedness. we describe the development and evaluation of the idylla™ prototype ebola virus test, a fully automated sample-to-result molecular diagnostic test for rapid detection of zaire ebolavirus (ebov) and sudan ebolavirus (sudv). | 2016 | 27247341 |
| immune memory to sudan virus: comparison between two separate disease outbreaks. | recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. according to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. however, a comprehensive protective immune profile has yet to be described. here, we examine cellular memory immune responses among survivors of two separate ebo ... | 2015 | 25569078 |
| synthetic antibodies with a human framework that protect mice from lethal sudan ebolavirus challenge. | the ebolaviruses cause severe and rapidly progressing hemorrhagic fever. there are five ebolavirus species; although much is known about zaire ebolavirus (ebov) and its neutralization by antibodies, little is known about sudan ebolavirus (sudv), which is emerging with increasing frequency. here we describe monoclonal antibodies containing a human framework that potently inhibit infection by sudv and protect mice from lethal challenge. the murine antibody 16f6, which binds the sudv envelope glyco ... | 2014 | 25140871 |
| 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 ... | 2013 | 23702199 |
| cathepsin b & l are not required for ebola virus replication. | ebola virus (ebov), family filoviridae, emerged in 1976 on the african continent. since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious public health concern and biothreat pathogen. the most pathogenic and best-studied species is zaire ebolavirus (zebov). ebov encodes one viral surface glycoprotein (gp), which is essential for replication, a determinant of pathogenicity and an important immunogen. gp mediates viral en ... | 2012 | 23236527 |
| a multiagent filovirus dna vaccine delivered by intramuscular electroporation completely protects mice from ebola and marburg virus challenge. | we evaluated the immunogenicity and protective efficacy of dna vaccines expressing the codon-optimized envelope glycoprotein genes of zaire ebolavirus, sudan ebolavirus, and marburg marburgvirus (musoke and ravn). intramuscular or intradermal delivery of the vaccines in balb/c mice was performed using the trigrid™ electroporation device. mice that received dna vaccines against the individual viruses developed robust glycoprotein-specific antibody titers as determined by elisa and survived lethal ... | 2012 | 22922764 |
| [study of gonadal hormone drugs in blocking filovirus entry of cells in vitro]. | this study was designed to discover filovirus entry inhibitors in a drug library of commercial medicines. one thousand and six hundred drugs were screened using the zebov-gp/hiv model, a pseudovirus formed by an hiv-core packed with the zaire ebola virus glycoprotein. we identified 12 gonadal hormone drugs with inhibitory activities in zebov-gp/hiv entry at final concentration of 10 μmol x l(-1). among them, three drugs exhibited strong activities with ic50 < 1 μmol x l(-1), such as toremifene c ... | 2015 | 27169275 |
| human survivors of disease outbreaks caused by ebola or marburg virus exhibit cross-reactive and long-lived antibody responses. | a detailed understanding of serological immune responses to ebola and marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. we examined antibodies from ebola or marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (np), viral protein 40 (vp40), envelope glycoprotein (gp), and inactivated whole virions from six species of filoviruses. all three outbreak cohorts ex ... | 2016 | 27335383 |
| correspondence of neutralizing humoral immunity and cd4 t cell responses in long recovered sudan virus survivors. | robust humoral and cellular immunity are critical for survival in humans during an ebolavirus infection. however, the interplay between these two arms of immunity is poorly understood. to address this, we examined residual immune responses in survivors of the sudan virus (sudv) outbreak in gulu, uganda (2000-2001). cytokine and chemokine expression levels in sudv stimulated whole blood cultures were assessed by multiplex elisa and flow cytometry. antibody and corresponding neutralization titers ... | 2016 | 27187443 |
| von willebrand factor is elevated in individuals infected with sudan virus and is associated with adverse clinical outcomes. | sudan virus (sudv) is a member of the filoviridae family that has been associated with sporadic outbreaks of human disease in sub-saharan africa. the filoviruses are notable for the high frequencies with which they cause both hemorrhagic manifestations and death in infected individuals. recently, we reported an extensive biomarker analysis of patient specimens from the gulu sudv outbreak. in that study, we found evidence of endothelial dysfunction and alterations of factors important to the coag ... | 2015 | 25387000 |
| profile and persistence of the virus-specific neutralizing humoral immune response in human survivors of sudan ebolavirus (gulu). | to better understand humoral immunity following ebolavirus infection, a serological study of the humoral immune response against the individual viral proteins of sudan ebolavirus (gulu) in human survivors was performed. an enzyme-linked immunosorbent assay specific for full-length recombinant viral proteins np, vp30, vp40, and gp1-649 (gp lacking the transmembrane domain) of sudan ebolavirus (gulu) was used as well as a plaque reduction neutralization test. serum samples from human survivors, wh ... | 2013 | 23585686 |
| sudan ebolavirus long recovered survivors produce gp-specific abs that are of the igg1 subclass and preferentially bind fcγri. | ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. to better understand immune correlates of protection by virus specific igg, we investigated the evolution of the fcγ receptors (fcγrs)-activating capabilities of antiviral igg in serum samples of long recovered survivors. to this end, longitudinal serum samples from survivors of sudan ebolavirus (sudv) infection, studied over years, were examined for the presence of ebola-gp specific igg subcl ... | 2017 | 28729706 |
| extensive serological survey of multiple african nonhuman primate species reveals low prevalence of immunoglobulin g antibodies to 4 ebola virus species. | bats are considered a reservoir species for ebola viruses, but nonhuman primates (nhps) have represented a source of infection in several outbreaks in humans. here we report serological screening of blood or fecal samples from monkeys (n = 2322) and apes (n = 2327). thirty-six nhp species from cameroon, democratic republic of the congo, and ivory coast were tested with a sensitive and specific luminex-based assay for immunoglobulin g antibodies to 4 ebola virus species. using the simultaneous pr ... | 2019 | 30657940 |
| a novel bacterium-like particle-based vaccine displaying the sudv glycoprotein induces potent humoral and cellular immune responses in mice. | sudan virus (sudv) causes severe lethal hemorrhagic fever in humans and nonhuman primates. the most effective and economical way to protect against sudan ebolavirus disease is prophylactic vaccination. however, there are no licensed vaccines to prevent sudv infections. in this study, a bacterium-like particle (blp)-based vaccine displaying the extracellular domain of the sudv glycoprotein (egp) was developed based on a gram-positive enhancer matrix-protein anchor (gem-pa) surface display system. ... | 2019 | 31835785 |
| sudan ebolavirus vp35-np crystal structure reveals a potential target for pan-filovirus treatment. | the filoviruses are etiological agents of life-threatening hemorrhagic fever with high mortality rate and risk of potential outbreak. among members of this family, the ebola (ebov), sudan (sudv), and marburg (marv) viruses are considered the most pathogenic for humans. the ebolavirus nucleoprotein (np) is the most abundant protein in infected cells and is essential for viral transcription and replication; thus, it represents an attractive target for therapeutic intervention. here, we present the ... | 2019 | 31337716 |
| serological detection of ebola virus exposures in native non-human primates of southern nigeria. | ebola viruses (family: filoviridae) are the cause of ebola virus disease (evd), a highly fatal illness characterised by haemorrhagic fever syndrome in both humans and non-human primates (nhps). west africa was the epicentre of the 2013-2015 evd epidemic which caused the death of over 11,000 people, including eight casualties in southern nigeria. antibodies to filoviruses have been detected among nhps in some countries, but there is no documented evidence of exposures to filoviruses among nhps in ... | 2018 | 30864758 |
| paratope duality and gullying are among the atypical recognition mechanisms used by a trio of nanobodies to differentiate ebolavirus nucleoproteins. | we had previously shown that three anti-marburg virus nanobodies (vhh or single-domain antibody [sdab]) targeted a cryptotope within an alpha-helical assembly at the nucleoprotein (np) c-terminus that was conserved through half a century of viral evolution. here, we wished to determine whether an anti-ebola virus sdab, that was cross-reactive within the ebolavirus genus, recognized a similar structural feature upstream of the ebolavirus np c-terminus. in addition, we sought to determine whether ... | 2019 | 31626803 |
| preservation of quaternary structure in thermostable, lyophilized filovirus glycoprotein vaccines: a search for stability-indicating assays. | the filoviruses zaire ebolavirus (ebov), marburg marburgvirus (marv), and sudan ebolavirus (sudv) are some of the most lethal infectious agents known. to date, the zaire ebolavirus vaccine (ervebo®) is the only united states food and drug administration (fda) approved vaccine available for any species of filovirus. however, the ervebo® vaccine requires cold-chain storage not to exceed -60 °c. such cold-chain requirements are difficult to maintain in low- and middle-income countries where filovir ... | 2020 | 32931778 |
| distinct immunogenicity and efficacy of poxvirus-based vaccine candidates against ebola virus expressing gp and vp40 proteins. | zaireandsudan ebolavirusspecies cause a severe disease in humans and non-human primates (nhps) characterized by high mortality rate. there are no licensed therapies or vaccines against ebola virus disease (evd), and the recent 2013-2016 outbreak in west africa highlighted the need of evd-specific medical countermeasures. here, we have generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against zaire ebolavirus (ebov) and sudan ebolavirus (sudv) bas ... | 2018 | 29514907 |
| single dose trivalent vesiculovax vaccine protects macaques from lethal ebolavirus and marburgvirus challenge. | previous studies demonstrated that a single intramuscular (im) dose of an attenuated vesicular stomatitis virus vector (vesiculovax™, rvsv-n4ct1) expressing the glycoprotein (gp) from the mayinga strain ofzaire ebolavirus(ebov) protected nonhuman primates (nhp) from lethal challenge with ebov kikwit and makona strains. here we studied the immunogenicity of an expanded range of attenuated rvsv vectors expressing filovirus gp in mice. based on data from those studies an optimal attenuated tri-vale ... | 2017 | 29142131 |
| investigation of ebolavirus exposure in pigs presented for slaughter in uganda. | in 2008, an outbreak of reston ebolavirus (restv) in pigs in the philippines expanded our understanding of the host range of ebolaviruses. subsequent experimental infections with the human-pathogenic species zaire ebolavirus (ebov) confirmed that pigs are susceptible to african species of ebolaviruses. pig keeping has become an increasingly important livelihood strategy throughout parts of sub-saharan africa, driven by increasing demand for pork. the growth in pig keeping is particularly rapid i ... | 2020 | 32915496 |
| lessons learned from zaire ebolavirus to help address urgent needs for vaccines against sudan ebolavirus and marburg virus. | the 2014-2016 ebola virus epidemic in west africa triggered extensive investments from public and private partners in an attempt to slow the spread of disease and bring the outbreak under control. this significantly accelerated the pace of development of countermeasures against zaire ebolavirus that enabled vaccines to be a part of an effective response to the most recent 2018-2019 outbreak in the democratic republic of the congo. however, there remain urgent and unmet needs for medical counterm ... | 2020 | 32275465 |
| the c-terminal domain of the sudan ebolavirus l protein is essential for rna binding and methylation. | the large (l) protein of ebola virus is a key protein for virus replication. its n-terminal region harbors the rna-dependent rna polymerase activity, and its c terminus contains a cap assembling line composed of a capping domain and a methyltransferase domain (mtase) followed by a c-terminal domain (ctd) of unknown function. the l protein mtase catalyzes methylation at the 2'-o and n-7 positions of the cap structures. in addition, the mtase of ebola virus can induce cap-independent internal aden ... | 2020 | 32269120 |
| the methyltransferase domain of the sudan ebolavirus l protein specifically targets internal adenosines of rna substrates, in addition to the cap structure. | mononegaviruses, such as ebola virus, encode an l (large) protein that bears all the catalytic activities for replication/transcription and rna capping. the c-terminal conserved region vi (crvi) of l protein contains a k-d-k-e catalytic tetrad typical for 2'o methyltransferases (mtase). in mononegaviruses, cap-mtase activities have been involved in the 2'o methylation and n7 methylation of the rna cap structure. these activities play a critical role in the viral life cycle as n7 methylation ensu ... | 2018 | 30192980 |