recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.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 (rvsv) that expresses an individual filovirus glycoprotein (gp) in place of the vsv glycoprotein (g). the main concern with all replication-competent vaccines, including the rvsv filovirus gp vectors, is their safety. to address this concern, we ...201222448291
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
immune response to marburg virus angola infection in nonhuman primates.the 2005 outbreak of marburg virus (marv) infection in angola was the most lethal marv infection outbreak in history, with a case-fatality rate (90%) similar to that for zaire ebolavirus (ebov) infection. however, very little is known about the pathogenicity of marv angola, as few studies have been conducted to date. therefore, the immune response was examined in marv angola-infected nonhuman primates.201525957966
mucosal immunization of cynomolgus macaques with the vsvdeltag/zebovgp vaccine stimulates strong ebola gp-specific immune responses.zaire ebolavirus (zebov) produces a lethal viral hemorrhagic fever in humans and non-human primates.200919440245
vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with ebola and marburg viruses.considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against ebola and marburg viruses. a vaccine based on recombinant vesicular stomatitis virus (vsv) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. while filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of ...200818930776
aerosol exposure to zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology.there is little known concerning the disease caused by zaire ebolavirus (zebov) when inhaled, the likely route of exposure in a biological attack. cynomolgus macaques, rhesus macaques, and african green monkeys were exposed to aerosolized zebov to determine which species might be the most relevant model of the human disease. a petechial rash was noted on cynomolgus and rhesus macaques after fever onset but not on african green monkeys. fever duration was shortest in rhesus macaques (62.7±16.3 h) ...201121651988
antibodies are necessary for rvsv/zebov-gp-mediated protection against lethal ebola virus challenge in nonhuman primates.ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. these viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. although not licensed for human use, recombinant vesicular stomatitis virus (rvsv) expressing the filovirus glycoprotein (gp) has been shown to protect macaques from ebola virus and marburg virus infections, both prophylactically an ...201323319647
infection with the makona variant results in a delayed and distinct host immune response compared to previous ebola virus variants.zaire ebolavirus (zebov) continues to pose a significant threat to human health as highlighted by the recent epidemic that originated in west africa and the ongoing outbreak in the democratic republic of the congo. although the zebov variant responsible for this epidemic (makona) shares significant genetic similarity with previously identified variants (kikwit and mayinga), recent reports suggest slower disease progression in nonhuman primates. however, the pathogenesis caused by the new variant ...201728852031
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
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
a vp35 mutant ebola virus lacks virulence but can elicit protective immunity to wild-type virus challenge.zaire ebolavirus (ebov) vp35 protein is a suppressor of type i interferon (ifn) production, an inhibitor of dendritic cell maturation, and a putative virulence determinant. here, a recombinant ebov encoding a mutant vp35 virus (vp35m) is demonstrated to activate rig-i-like receptor signaling and innate antiviral pathways. when inoculated into cynomolgus macaques, vp35m exhibits dramatic attenuation as compared to wild-type ebov (wtebov), with 20 or 300 times the standard 100% lethal challenge do ...201931533029
rvsvĪ“g-zebov-gp (also designated v920) recombinant vesicular stomatitis virus pseudotyped with ebola zaire glycoprotein: standardized template with key considerations for a risk/benefit assessment.the brighton collaboration viral vector vaccines safety working group (v3swg) was formed to evaluate the safety and characteristics of live, recombinant viral vector vaccines. a recent publication by the v3swg described live, attenuated, recombinant vesicular stomatitis virus (rvsv) as a chimeric virus vaccine for hiv-1 (clarke et al., 2016). the rvsv vector system is being explored as a platform for development of multiple vaccines. this paper reviews the molecular and biological features of th ...201931384731
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 ...200919386702
transcriptome analysis of circulating immune cell subsets highlight the role of monocytes in zaire ebola virus makona pathogenesis.existing models of ebola virus disease (evd) suggest antigen-presenting cells are initial targets ofzaire ebolavirus(zebov).in vitrostudies have shown that zebov infection of monocytes and macrophages results in the production of inflammatory mediators, which may cause lymphocyte apoptosis. however, these findings have not been corroborated byin vivostudies. in this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, t-cells, and b-cells isolated fr ...201729123522
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