Publications

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in vitro evaluation of antisense rna efficacy against filovirus infection, by use of reverse genetics.recent reports indicate the possibility of using small interfering rnas (sirnas) to treat filovirus infections; however, they also show that the effectiveness of this approach is highly dependent on target site selection. therefore, we explored the application of minigenomes as screening tools to identify functional sirna targets under biosafety level 2 conditions.200717940974
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 ...201525957964
animal models for ebolavirus countermeasures discovery: what defines a useful model?ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (nhp) in africa. the zaire ebolavirus outbreak in 2014, which continues to greatly affect western africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. after almost a year of research at an increased pace to find and test vaccines ...201526004783
experimental aerosolized guinea pig-adapted zaire ebolavirus (variant: mayinga) causes lethal pneumonia in guinea pigs.eight guinea pigs were aerosolized with guinea pig-adapted zaire ebolavirus (variant: mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. intracytoplasmic inclusion bodies were observed in many alveolar macrophages. perivasculitis was note ...201524829285
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 ...201323670573
vsvδg/ebov gp-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted ebola virus infection.members of the species zaire ebolavirus cause severe hemorrhagic fever with up to a 90% mortality rate in humans. the vsvδg/ebov gp vaccine has provided 100% protection in the mouse, guinea pig, and nonhuman primate (nhp) models, and has also been utilized as a post-exposure therapeutic to protect mice, guinea pigs, and nhps from a lethal challenge of ebola virus (ebov). ebov infection causes rapid mortality in human and animal models, with death occurring as early as 6 days after infection, sug ...201525494457
vaccines. an ebola whole-virus vaccine is protective in nonhuman primates.zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in west africa. previously, we showed that a whole ebola virus (ebov) vaccine based on a replication-defective ebov (ebovδvp30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted ebov. here, we demonstrate that ebovδvp30 protects nonhuman primates against lethal infection with ebov. although ebovδvp30 is replication-incompetent, we additionally inactivated the vaccine wi ...201525814063
modeling the disease course of zaire ebolavirus infection in the outbred guinea pig.rodent models that accurately reflect human filovirus infection are needed as early screens for medical countermeasures. prior work in rodents with the zaire species of ebola virus (zebov) primarily used inbred mice and guinea pigs to model disease. however, these inbred species do not show some of the important features of primate zebov infection, most notably, coagulation abnormalities.201526038397
the challenge of using experimental infectivity data in risk assessment for ebola virus: why ecology may be important.analysis of published data shows that experimental passaging of zaire ebolavirus (ebov) in guinea pigs changes the risk of infection per plaque-forming unit (pfu), increasing infectivity to some species while decreasing infectivity to others. thus, a pfu of monkey-adapted ebov is 10(7) -fold more lethal to mice than a pfu adapted to guinea pigs. the first conclusion is that the infectivity of ebov to humans may depend on the identity of the donor species itself and, on the basis of limited epide ...201626480954
immune parameters correlate with protection against ebola virus infection in rodents and nonhuman primates.ebola virus causes severe hemorrhagic fever in susceptible hosts. currently, no licensed vaccines or treatments are available; however, several experimental vaccines have been successful in protecting rodents and nonhuman primates (nhps) from the lethal zaire ebolavirus (zebov) infection. the objective of this study was to evaluate immune responses correlating with survival in these animals after lethal challenge with zebov. knockout mice with impaired ability to generate normal t and/or b cell ...023115355
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
impact of systemic or mucosal immunity to adenovirus on ad-based ebola virus vaccine efficacy in guinea pigs.approximately 35% of the north american population and an estimated 90% of the sub-saharan african population have antibodies against adenovirus serotype 5 (adhu5) that are capable of neutralizing adhu5-based vaccines. in mice, intranasal delivery of adhu5 expressing the zaire ebolavirus glycoprotein human adenovirus serotype 5 (ad) containing the genes for the zaire ebolavirus glycoprotein (zgp) under the expressional control of a cytomegalovirus immediate early promoter (cmv)) can bypass syste ...201121987739
genetic factors of ebola virus virulence in guinea pigs.zaire ebolavirus (zebov) causes severe hemorrhagic fever in primates, whereas in guinea pigs it induces a nonlethal infection with a mild fever and subsequent recovery. we performed 7 selective passages in guinea pigs resulted in obtaining of guinea pig-adapted strain (gpa-p7) strain. by the 7th passage, the infection with ebov induced a lethal disease in animals accompanied by the characteristic hematological changes: leukocytosis (primarily due to neutrophilia) as well as pronounced deficienci ...201020654661
enhanced protection against ebola virus mediated by an improved adenovirus-based vaccine.the ebola virus is transmitted by direct contact with bodily fluids of infected individuals, eliciting death rates as high as 90% among infected humans. currently, replication defective adenovirus-based ebola vaccine is being studied in a phase i clinical trial. another ebola vaccine, based on an attenuated vesicular stomatitis virus has shown efficacy in post-exposure treatment of nonhuman primates to ebola infection. in this report, we modified the common recombinant adenovirus serotype 5-base ...200919390586
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