poxviruses isolated from clinically ill and asymptomatically infected monkeys and a chimpanzee.poxviruses were isolated from the kidneys of an outwardly healthy chimpanzee trapped in an area of the democratic republic of the congo where a case of monkeypox had recently occurred in man, from the kidneys of clinically healthy cynomolgus monkeys in a colony in the netherlands, and from monkeys suffering from monkeypox during outbreaks in colonies in the usa. it was established that two of the three viruses isolated from animals asymptomatically infected-namely, strain chimp-9 from the chimpa ...19724340220
modified vaccinia virus ankara protects macaques against respiratory challenge with monkeypox virus.the use of classical smallpox vaccines based on vaccinia virus (vv) is associated with severe complications in both naive and immune individuals. modified vaccinia virus ankara (mva), a highly attenuated replication-deficient strain of vv, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. here we directly compare the efficacies of mva alone and in combination with classical vv-based vaccines in a cynomolgus macaque ...200515919938
virulence differences between monkeypox virus isolates from west africa and the congo basin.studies indicate that west african and congo basin isolates of monkeypox virus (mpxv) are genetically distinct. here, we show congo basin mpxv-zai-v79 is more virulent for cynomolgus monkeys as compared to presumed west african mpxv-cop-58. this finding may explain the lack of case-fatalities in the u.s. 2003 monkeypox outbreak, which was caused by a west african virus. virulence differences between west african and congo basin mpxv are further supported by epidemiological analyses that observed ...200516023693
antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.there is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. for this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called hpmpc ...200616341204
clonal vaccinia virus grown in cell culture fully protects monkeys from lethal monkeypox challenge.the potential use of smallpox as an agent of bioterrorism has renewed interest in the development of a modern vaccine capable of replacing the standard dryvax vaccine. vaccinia virus (acam2000), clonally isolated from dryvax and manufactured in cell culture, was tested for immunogenicity and protective activity in a non-human primate model. cynomolgus monkeys vaccinated with acam2000, dryvax, or acam2000 diluent (control) were challenged 2 months post-vaccination with a lethal, intravenous dose ...200818077063
pharmacodynamics of cidofovir for vaccinia virus infection in an in vitro hollow-fiber infection model system.variola major virus remains a potent weapon of bioterror. there is currently an investigational-new-drug application for cidofovir for the therapy of variola major virus infections. stittelaar and colleagues compared the levels of effectiveness of postexposure smallpox vaccination (elstree-rivm) and antiviral treatment with cidofovir or an acyclic nucleoside phosphonate analogue 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidine (hpmpo-dapy) after lethal intratracheal infection of cynomolgus m ...200918852271
molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 1970s. because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. thus, there is a need for new, safe, and effective orthopoxvirus vaccines. alphavirus replicon vectors, derived from strains of venezuelan equin ...200919833247
application of the ibis-t5000 pan-orthopoxvirus assay to quantitatively detect monkeypox viral loads in clinical specimens from macaques experimentally infected with aerosolized monkeypox virus.monkeypox virus (mpxv), a member of the family poxviridae and genus orthopoxvirus, causes a smallpox-like disease in humans. a previously described pan-orthopoxvirus assay, based on a broad-range polymerase chain reaction (pcr) coupled with electrospray ionization mass spectrometry (pcr/esi-ms), was evaluated for its ability to detect mpxv from spiked human and aerosol-infected cynomolgous macaque (macaca fascicularis) samples. detection of mpxv dna from macaque tissue, blood, and spiked human b ...201020134011
animal models of orthopoxvirus infection.smallpox was one of the most devastating diseases known to humanity. although smallpox was eradicated through a historically successful vaccination campaign, there is concern in the global community that either variola virus (varv), the causative agent of smallpox, or another species of orthopoxvirus could be used as agents of bioterrorism. therefore, development of countermeasures to orthopoxvirus infection is a crucial focus in biodefense research, and these efforts rely on the use of various ...201020682806
comparative analysis of monkeypox virus infection of cynomolgus macaques by the intravenous or intrabronchial inoculation route.monkeypox virus (mpxv) infection has recently expanded in geographic distribution and can be fatal in up to 10% of cases. the intravenous (i.v.) inoculation of nonhuman primates (nhps) results in an accelerated fulminant disease course compared to that of naturally occurring mpxv infection in humans. alternative routes of inoculation are being investigated to define an nhp model of infection that more closely resembles natural disease progression. our goal was to determine if the intrabronchial ...201021147922
proteomic basis of the antibody response to monkeypox virus infection examined in cynomolgus macaques and a comparison to human smallpox vaccination.monkeypox is a zoonotic viral disease that occurs primarily in central and west africa. a recent outbreak in the united states heightened public health concerns for susceptible human populations. vaccinating with vaccinia virus to prevent smallpox is also effective for monkeypox due to a high degree of sequence conservation. yet, the identity of antigens within the monkeypox virus proteome contributing to immune responses has not been described in detail. we compared antibody responses to monkey ...201021209900
a novel respiratory model of infection with monkeypox virus in cynomolgus macaques.variola, the causative agent of smallpox, and the related monkeypox virus are both select agents that, if purposefully released, would cause public panic and social disruption. for this reason research continues in the areas of animal model and therapeutic development. orthopoxviruses show a widely varying degree of host specificity, making development of accurate animal models difficult. in this paper, we demonstrate a novel respiratory infection technique that resulted in "classic" orthopox di ...201121389129
infection of cynomolgus macaques with a recombinant monkeypox virus encoding green fluorescent protein.monkeypox virus (mpxv) causes a vesiculopustular rash illness resembling smallpox in humans and produces a similar disease in nonhuman primates. to enhance the ability of researchers to study experimental mpxv infections, we inserted a gene encoding green fluorescent protein (gfp) into monkeypox virus zaire-79. wild-type and mpxv-gfp replicated with similar kinetics in cell culture and caused a similar disease when injected intravenously into cynomolgus macaques. in mpxv-gfp-infected animals, ex ...201121814864
attenuated nycbh vaccinia virus deleted for the e3l gene confers partial protection against lethal monkeypox virus disease in cynomolgus macaques.the new york city board of health (nycbh) vaccinia virus is the currently licensed vaccine for use in the us against smallpox. the vaccine under investigation in this study has been attenuated by deletion of the innate immune evasion gene, e3l, and shown to be protective in homologous virus mouse challenge and heterologous virus mouse and rabbit challenge models. in this study we compared nycbh deleted for the e3l gene (nycbhδe3l) to nycbh for the ability to induce phosphorylation of proinflamma ...201122001879
poxvirus antigen staining of immune cells as a biomarker to predict disease outcome in monkeypox and cowpox virus infection in non-human primates.infection of non-human primates (nhps) such as rhesus and cynomolgus macaques with monkeypox virus (mpxv) or cowpox virus (cpxv) serve as models to study poxvirus pathogenesis and to evaluate vaccines and anti-orthopox therapeutics. intravenous inoculation of macaques with high dose of mpxv (>1-2×10(7) pfu) or cpxv (>10(2) pfu) results in 80% to 100% mortality and 66 to 100% mortality respectively. here we report that nhps with positive detection of poxvirus antigens in immune cells by flow cyto ...201323577120
pathogenesis of fulminant monkeypox with bacterial sepsis after experimental infection with west african monkeypox virus in a cynomolgus monkey.the pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. this study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (macaca fascicularis). in our previous study (saijo et al., 2009, j gen virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus liberia strain, west african strain. one exhibited typical monkeypox-relat ...201425120821
assessment of the protective effect of imvamune and acam2000 vaccines against aerosolized monkeypox virus in cynomolgus support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, acam2000 and imvamune, for protection against disease. animals vaccinated with a single immunization of imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of imvamune or a single immunization with acam2000 were p ...201323658452
inhalational monkeypox virus infection in cynomolgus inhalation exposure system was characterized to deliver aerosolized monkeypox virus (mpxv), and a non-human primate (nhp) inhalation monkeypox model was developed in cynomolgus macaques. a head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. the aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable ...201223061051
experimental infection of cynomolgus macaques (macaca fascicularis) with aerosolized monkeypox virus.monkeypox virus (mpxv) infection in humans results in clinical symptoms very similar to ordinary smallpox. aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. therefore, an animal model for aerosol exposure to mpxv is needed to test medical countermeasures. to characterize the pathogenesis in cynomolgus macaques (macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized mpxv. blood was collected th ...201020862223
smallpox vaccine with integrated il-15 demonstrates enhanced in vivo viral clearance in immunodeficient mice and confers long term protection against a lethal monkeypox challenge in cynomolgus monkeys.despite the eradication of smallpox, there is heightened concern that it could be reintroduced as a result of intentional release of variola major virus through an act of bioterrorism. the live vaccine that was pivotal in the eradication of smallpox though considered a gold standard for its efficacy still retains sufficient residual virulence that can cause life-threatening sequelae especially in immune deficient individuals. therefore, a safer smallpox vaccine that can match the efficacy of fir ...201020728526
the pathology of experimental aerosolized monkeypox virus infection in cynomolgus monkeys (macaca fascicularis).cynomolgus monkeys (macaca fascicularis) were exposed by fine-particle aerosol to lethal doses of monkeypox virus, zaire strain. death, attributable to fibrinonecrotic bronchopneumonia, occurred 9 to 17 days postexposure. lower airway epithelium served as the principal target for primary infection. the relative degree of involvement among lymphoid tissues suggested that tonsil, mediastinal, and mandibular lymph nodes were also infected early in the course of the disease, and may have served as a ...200111742030
sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox evaluate new vaccines when human efficacy studies are not possible, the fda's "animal rule" requires well-characterized models of infection. thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. cynomolgus macaques were exposed to aerosolized monkeypox virus (10(5) pfu). clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, ...201525653439
treatment with the smallpox antiviral tecovirimat (st-246) alone or in combination with acam2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.the therapeutic efficacies of smallpox vaccine acam2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. postexposure administration of acam2000 alone did not provide any protection against severe monkeypox disease or mortality. in contrast, postexposure treatment with tecovirimat alone or in combination with acam2000 provided full protection. additionally, tecovirimat treatmen ...201525896687
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