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[immunobiological properties of vp24 protein of ebola virus expressed by recombinant vaccinia virus].immunological and biochemical parameters were studied in guinea pigs immunized with recombinant vaccinia virus containing full-sized gene of ebola virus vp24 protein and then infected with virulent strain of ebola virus. the majority of the studied parameters changed similarly in guinea pigs immunized with recombinant vaccinia virus and control guinea pigs inoculated with vaccinia virus both before and after challenge with ebola virus. however, in animals immunized with recombinant vaccinia viru ...19979297340
[effect of an infections dose of the ebola virus on survivability and immunologic indicators in guinea pigs].analysis of the time course of immunological parameters in intact guinea pigs and animals immunized with inactivated ebola virus (ev) inoculated with high and low doses of ev strain lethal for guinea pigs showed that high doses induced a higher resistance of the lymphocytic component of immunity than low doses, but activation of the neutrophil phagocytosis was far less expressed after high doses than after low ones. this indicates a qualitative effect of the infective dose of ev on the developme ...199910544449
[study of the phagocytic ability of blood polymorphonuclear leukocytes from rabbits and guinea pigs upon administering ebola virus].study of the phagocytic activity of polymorphonuclear leukocytes (pmnl) of rabbits resistant to ebola virus and guinea pigs susceptible to it, repeatedly challenged with live or inactivated ebola virus in accordance with the immunization protocols, showed a much higher phagocytic activity in animals resistant to the virus than in those susceptible to it. such behavior of pmnl in guinea pigs may be explained by the absence of the necessary cytokine background activating the neutrophils.19979182399
[attempts to develop a vaccine against ebola fever].data on the immunopathogenesis of ebola fever in laboratory animals are presented and the efficacy of some methods of vaccine prophylaxis discussed. antiviral immunity induced in guinea pigs by injection of inactivated viral agents did not protect them from infection, whereas injections of a nonlethal strain of the virus in ascending doses led to the formation of immunity preventing the development of disease upon inoculation with a lethal strain in high doses. the role of some viral peptides in ...19958686261
[study of the treatment-prophylactic effect of immunomodulators in experimental infections, caused by marburg, ebola, and venezuelan equine encephalitis viruses].therapeutic and prophylactic effects of immunomodifiers ridostin, reaferon, and polyribonate used alone and in various combinations were assessed in experiments on guinea pigs infected with venezuelan equine encephalomyelitis (vee) (strain trinidad), marburg (strain popp), and ebola (m/c-8 variant of zaire strain) viruses at doses 5 to 20 respiratory ld50 through the respiratory airways. urgent prophylactic simultaneous intramuscular and intranasal administration of ridostin protected the animal ...19979424849
[light microscopy study of ebola virus hepatitis in guinea pigs]. 19817347447
detection of antibodies against the four subtypes of ebola virus in sera from any species using a novel antibody-phage indicator assay.the natural host for ebola virus, presumed to be an animal, has not yet been identified despite an extensive search following several major outbreaks in africa. a straightforward approach used to determine animal contact with ebola virus is by assessing the presence of specific antibodies in serum. this approach however has been made very difficult by the absence of specific reagents required for the detection of antibodies from the majority of wild animal species. in this study, we isolated a h ...200212350354
pre- and postexposure prophylaxis of ebola virus infection in an animal model by passive transfer of a neutralizing human antibody.a neutralizing human monoclonal antibody, kz52, protects guinea pigs from lethal ebola zaire virus challenge. administration before or up to 1 h after challenge resulted in dose-dependent protection by the antibody. interestingly, some antibody-treated animals survived despite developing high-level viremia, suggesting that the mechanism of protection by kz52 may extend beyond reduction of viremia by virus neutralization. kz52 is a promising candidate for immunoprophylaxis of ebola virus infectio ...200212021376
ebola virus infection in guinea pigs: presumable role of granulomatous inflammation in pathogenesis.an approach combining virology with light and electron microscopy was used to study the organs of guinea pigs during nine serial passages of ebola virus, strain zaire. it was observed that the wild type of ebola virus causes severe granulomatous inflammation in the liver and reproduces in the cells of the mononuclear phagocyte system (mps). based on morphological characterization, two types of virus-cell interactions were demonstrated. the obtained data evidenced for heterogeneity of the populat ...19968678836
[dynamics of complement hemolytic activity in experimental ebola infection].the dynamic hemolytic activity of complements (hac) was investigated in blood of guinea pigs in lethal and non-lethal ebola infection. the increasing hac dynamic activity in the animal blood was found to correlate with the infection lethal course. hac as observed in animals with lethal infection was sweepingly increasing after they, were infected with ebola virus, and yet after 15 hours from the infection time the complement activity parameters topped 2-fold the basic values in 100% of guinea pi ...200415106379
[the morphological changes in ebola infection in guinea pigs].ebola virus reproduction and morphological lesions were investigated in infected guinea pigs by electron microscopy. the liver was found to be the main target organ, whereas in other internal organs the pathological changes were insignificant. ebola virus reproduction was demonstrated only in cells of the mononuclear phagocyte system.19938236944
[sensitizing and virus-neutralizing characteristics of goat immunoglobulins to ebola virus].sensitizing and virus-neutralizing properties of igg isolated from the sera of goats immunized with ebola virus and a relevant gammaglobulin prepared by ethanol fractionation were compared. the ratio of the virus-neutralizing activities of subclasses igg2, igg1a, and igg1b was 100:10:1. anaphylactogenic activity of igg2 in the immediate type hypersensitivity test in guinea pigs was 2-fold lower than that of igg1a and igg1b. goat gammaglobulin to ebola virus, consisting from igg2 antibodies by mo ...200212046470
[the ultrastructural changes in guinea pig organs during the serial passage of the ebola virus].morphological study of internal organs of guinea pigs inoculated with ebola virus at 2-8 passages was carried out. in the course of these passages the number of infected cells and virus particles in the organs was shown to increase, and the destructive changes in organs became more pronounced. in the 1st-3rd passages ebola virus replication was observed in macrophagal cells only but beginning from the 4th passage of virus reproduction was found also in hepatocytes, spongiocytes, and fibroblasts.19938236945
[ebola virus reproduction in cell cultures].ebola-zaire virus production in vero and bgm cells was studied. the cpe developed in both cell cultures. the cell monolayer destruction by 80-90% was seen at a low multiplicity of infection in 7-8 days after virus inoculation. an overlay composition was developed for virus titration using plaque assay. the plaque production was shown to be directly proportional to the virus dose. the curve of ebola virus production in vero cell culture fluid was determined. at a multiplicity of infection of 0.01 ...19921279896
pathogenesis of experimental ebola zaire virus infection in balb/c mice.guinea-pigs and non-human primates have traditionally been used as animal models for studying ebola zaire virus (ebo-z) infections. the virus was also recently adapted to the stage of lethal virulence in balb/c mice. this murine model is now in use for testing antiviral medications and vaccines. however, the pathological features of ebo-z infection in mice have not yet been fully described. to identify sites of viral replication and characterize sequential morphological changes in balb/c mice, a ...200111798240
antibody to ebola virus in guinea pigs: tandala, zaire.a case-control study was conducted to investigate the findings of antibody to ebola virus in the serum of a guinea pig from tandala, zaire. case households, defined by the possession of one or more guinea pigs, were compared to neighboring households without guinea pigs. seven (5.1%) of 138 samples of human sera and 36 (26%) of 138 samples of guinea pig sera had antibody to ebola virus. there was no clustering of seropositivity among humans or guinea pigs within households, nor was there any ass ...19826750007
prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug.ribavirin, a broad-spectrum antiviral drug, is active against hemorrhagic fever viruses (with the exception of ebola virus) in cell culture systems. in model infections with arenaviruses in guinea pigs and monkeys, ribavirin has demonstrated both prophylactic and therapeutic efficacy. in therapeutic studies it has not prevented late-onset neurologic disease. in human cases of lassa fever, it significantly reduces mortality when administered before day 7 of illness to persons at high risk. in rod ...19892546248
a comparative study of strains of ebola virus isolated from southern sudan and northern zaire in 1976.during the 1976 ebola virus outbreak in sudan, the investigations team gained the impression that fewer haemorrhagic manifestations and few fatalities occurred during the later stages of the epidemic after the virus had undergone several generations in man. this impression was also noted in guinea pigs experimentally infected with sudanese and zairean strains of ebola virus. the virulence of the sudanese isolates was less intense than isolates emanating from zaire. similar findings were seen in ...19806165800
molecular characterization of guinea pig-adapted variants of ebola virus.serial passage of initially nonlethal ebola virus (ebov) in outbred guinea pigs resulted in the selection of variants with high pathogenicity. nucleotide sequence analysis of the complete genome of the guinea pig-adapted variant 8mc revealed that it differed from wild-type virus by eight mutations. no mutations were identified in nontranscribed regions, including leader, trailer, and intragenic sequences. among noncoding regions the only base change was found in the vp30 gene. two silent base ch ...200011062045
individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with lassa and ebola viruses.lassa and ebola viruses cause acute, often fatal, hemorrhagic fever diseases, for which no effective vaccines are currently available. although lethal human disease outbreaks have been confined so far to sub-saharan africa, they also pose significant epidemiological concern worldwide as demonstrated by several instances of accidental importation of the viruses into north america and europe. in the present study, we developed experimental individual vaccines for lassa virus and bivalent vaccines ...200111689649
development of a model for marburgvirus based on severe-combined immunodeficiency mice.the filoviruses, ebola (ebov) and marburg (marv), cause a lethal hemorrhagic fever. human isolates of marv are not lethal to immmunocompetent adult mice and, to date, there are no reports of a mouse-adapted marv model. previously, a uniformly lethal ebov-zaire mouse-adapted virus was developed by performing 9 sequential passages in progressively older mice (suckling to adult). evaluation of this model identified many similarities between infection in mice and nonhuman primates, including viral t ...200717961252
ebola virus glycoprotein demonstrates differential cellular localization in infected cell types of nonhuman primates and guinea pigs.in vitro studies have previously shown that ebola virus glycoprotein (gp) is rapidly processed and largely released from infected cells, whereas other viral proteins, such as vp40, accumulate within cells.200111300932
cutaneous dna vaccination against ebola virus by particle bombardment: histopathology and alteration of cd3-positive dendritic epidermal cells.we analyzed the localization of gold particles, expression of immunogenic protein, and histopathologic changes after vaccinating guinea pigs and mice with a dna vaccine to the ebola virus glycoprotein administered by cutaneous particle bombardment. gold particles were deposited in all layers of the epidermis and in the dermis. those in the epidermis were lost as the damaged layers sloughed, while those in the dermis were phagocytized by macrophages. glycoprotein was demonstrated by immunohistoch ...200111280377
recombinant rna replicons derived from attenuated venezuelan equine encephalitis virus protect guinea pigs and mice from ebola hemorrhagic fever virus.rna replicons derived from an attenuated strain of venezuelan equine encephalitis virus (vee), an alphavirus, were configured as candidate vaccines for ebola hemorrhagic fever. the ebola nucleoprotein (np) or glycoprotein (gp) genes were introduced into the vee rna downstream from the vee 26s promoter in place of the vee structural protein genes. the resulting recombinant replicons, expressing the np or gp genes, were packaged into vee replicon particles (np-vrp and gp-vrp, respectively) using a ...200010924796
[dynamics of immunologic indicators in guinea pigs upon administering various preparations of the ebola virus].immunological and hematological values are analyzed in guinea pigs infected with ebola virus (ev) strain weakly pathogenic for these animals, inactivated ev, and ev strain adapted to guinea pigs and causing a lethal infection in them. the disease induced by lethal ev differed from that induced by other ev strains. blastic wave in lymphoid organs in the absence of antibodies to ev detected by enzyme immunoassay, elimination of circulating immune complexes, and appearance of eosinophils in the blo ...19989791881
evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental ebola virus infections.a passive immunization strategy for treating ebola virus infections was evaluated using balb/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. guinea pigs were completely protected by injection of hyperimmune equine igg when treatment was initiated early but not after viremia had developed. in contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. in monkeys treated with one dose of igg on day 0, onset of illness and viremia was ...19999988188
preparation and use of hyperimmune serum for prophylaxis and therapy of ebola virus infections.to obtain hyperimmune serum appropriate for the treatment of filovirus infection, methods were developed to immunize nonsusceptible animals with live ebola (ebo) virus preparations. immune plasma with high elisa and neutralization-specific antibody titers was obtained by multiple immunization of sheep and goats with preparations of live ebo virus. goat immunoglobulin was prepared by cohn's method and tested on guinea pigs, using an ebo virus strain that is highly pathogenic for guinea pigs. prop ...19999988187
[change in biochemical and hemostatic indicators in guinea pigs upon administering ebola virus preparations].the biochemical and hemostatic parameters were compared in guinea pigs after inoculation of ebola virus strains lethal and nonlethal for them and of inactivated antigen of this virus. the time course of the main hemostatic and biochemical parameters in animals challenged with the lethal strain of ebola virus differed much from that in other groups. this permits us to hypothesize that modification of the virus in the course of adaptation to the host results in the appearance of properties boostin ...19979304298
[study of the functional role of mutation in the guinea pig-adapted ebola virus genome on a drosophila melanogaster model].ebola virus virulence in guinea pigs, which appears through virus adaptation to this animal host, correlates with substitutions in the gene encoding vp24 protein. in particular, the substitution his-->tyr186 was found when obtaining strain 8 ms. an attempt was made to clarify the functional role of this substitution in a transgenic fruit fly model. using the drosophila transformation technique provided transgenic strains that contained genomic insertions of wild-type ebola virus vp24 gene and th ...201121427954
haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of ebola zaire virus.ebola zaire virus from the 1976 outbreak (ebo-z) was recently adapted to the stage of lethal virulence in balb/c mice through serial passage. in the present study, various parameters were examined in groups of mice and guinea-pigs and in three rhesus monkeys after infection with mouse-adapted ebo-z. the virus caused fatal disease not only in mice but also in guinea-pigs, in which the course of illness resembled that produced by guinea-pig-adapted ebo-z. mice, guinea-pigs and monkeys showed simil ...200111798241
evaluation in nonhuman primates of vaccines against ebola virus.ebola virus (ebov) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. no vaccines or treatments are available for human use. we evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal ebov infection. the following immunogens were used: rna replicon particles derived from an attenuated strain of venezuelan equine encephalitis virus (veev) expressing ebov glycoprotein and nucleoprotein ...200211996686
comparison of the protective efficacy of dna and baculovirus-derived protein vaccines for ebola virus in guinea pigs.the filoviruses ebola virus (ebov) and marburg virus (marv) cause severe hemorrhagic fever in humans for which no vaccines are available. previously, a priming dose of a dna vaccine expressing the glycoprotein (gp) gene of marv followed by boosting with recombinant baculovirus-derived gp protein was found to confer protective immunity to guinea pigs (hevey et al., 2001. vaccine 20, 568-593). to determine whether a similar prime-boost vaccine approach would be effective for ebov, we generated and ...200312686428
[the efficacy of the emergency prophylactic and therapeutic actions of immunomodulators in experimental filovirus infections].the study of the preventive and therapeutic action of some immunomodulators (ridostin, reaferon and polyribonate) used alone and in combinations was conducted on laboratory animals infected aerogenically by marburg or ebola virus. it was found that special preventive intranasal and intramuscular administration of ridostin provided protection of the animals infected by marburg virus (p = 0.1) and an increase in their mean lifespan by 2.4 days (p = 0.15). in the ebola infection combined administra ...19958534175
[strain differences related to ebola virus reproduction in peritoneal macrophages and in aorta explants of guinea pigs].reproduction of the ebola strains (es) virus causing lethality in guinea pigs as well as in peritoneal macrophages and aorta explants of animals was investigated in vitro and in vivo; besides, production of interferon-gamma (ifn-gamma) and of tumor necrosis factor-alpha (tnf-alpha) by macrophages and endotheliocytes of guinea pigs was also studied. the interplay "macrophage--es" by the example of 2 models of susceptibility to es demonstrates that the es lethality is not unambiguously related onl ...200415106377
marburg virus-like particles protect guinea pigs from lethal marburg virus infection.ongoing outbreaks of filoviruses in africa and concerns about their use in bioterrorism attacks have led to intense efforts to find safe and effective vaccines to prevent the high mortality associated with these viruses. we previously reported the generation of virus-like particles (vlps) for the filoviruses, marburg (marv) and ebola (ebov) virus, and that vaccinating mice with ebola vlps (evlps) results in complete survival from a lethal ebov challenge. the objective of this study was to determ ...200415308377
pathogenesis of experimental ebola virus infection in guinea pigs.the subtype zaire of ebola (ebo) virus (mayinga strain) was adapted to produce lethal infections in guinea pigs. in many ways, the disease was similar to ebo infections in nonhuman primates and humans. the guinea pig model was used to investigate the pathologic events in ebo infection that lead to death. analytical methods included immunohistochemistry, in situ hybridization, and electron microscopy. cells of the mononuclear phagocyte system, primarily macrophages, were identified as the early a ...19999988186
immunization for ebola virus infection.infection by ebola virus causes rapidly progressive, often fatal, symptoms of fever, hemorrhage and hypotension. previous attempts to elicit protective immunity for this disease have not met with success. we report here that protection against the lethal effects of ebola virus can be achieved in an animal model by immunizing with plasmids encoding viral proteins. we analyzed immune responses to the viral nucleoprotein (np) and the secreted or transmembrane forms of the glycoprotein (sgp or gp) a ...19989427604
[developing methods of specific heterologic immunoglobulins preparation for urgent prevention of ebola fever and study of their properties].methods for preventing and treating ebola virus hemorrhagic fever are not still available despite the fact that this virus have been studied for 20 years. methods of immunization of the animals (sheep, goats) non-susceptible to ebola virus with live virus preparations were developed to obtain the hyperimmune anti-ebola virus sera required to have highly immune antivirus gamma-globulins. these methods made it possible to obtain the immune sera having high virus-neutralizing antibodies. caprine im ...19989633237
[hematological and immunological parameters during ebola virus passages in guinea-pigs].the trend in hematological and immunological parameters during ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. the increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes ...200616929596
[composition and immunochemical properties of goat immunoglobulins against the ebola virus].serum samples containing ebola virus neutralizing antibodies were prepared by prolonged immunization of goats with 10% liver homogenate from guinea pigs infected with ebola virus. differences in igg fractions of normal and hyperimmune caprine blood sera were detected. analytical chromatography on polysil sa and immunodiffusion showed the presence of three igg-containing fractions in hyperimmune sera. immunochemical properties of these fractions were studied by solid-phase enzyme immunoassay and ...19947716910
virus-like particles exhibit potential as a pan-filovirus vaccine for both ebola and marburg viral infections.a safe and effective pan-filovirus vaccine is highly desirable since the filoviruses ebola virus (ebov) and marburg virus (marv) cause highly lethal disease typified by unimpeded viral replication and severe hemorrhagic fever. previously, we showed that expression of the homologous glycoprotein (gp) and matrix protein vp40 from a single filovirus, either ebov or marv, resulted in formation of wild-type virus-like particles (vlps) in mammalian cells. when used as a vaccine, the wild-type vlps pro ...200515811650
treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from ebola virus infection.recent successes with monoclonal antibody cocktails zmapp(tm) and mil77 against ebola virus (ebov) infections have reignited interest in antibody-based therapeutics. since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. we produced purified equine antisera from horses hyperimmunized with ebov virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. balb/c mice were given ...201627067649
effective post-exposure treatment of ebola infection.ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in central africa and a potential for use as a biological weapon. there is no vaccine or treatment licensed for human use. in the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. in this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus ...200717238284
chimeric human parainfluenza virus bearing the ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against ebola virus challenge.we generated a new live-attenuated vaccine against ebola virus (ebov) based on a chimeric virus hpiv3/deltaf-hn/ebogp that contains the ebov glycoprotein (gp) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (hpiv3). electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of ebov and a particle size and shape resembling those of hpiv3. when hpiv3/deltaf-hn/ebogp was ...200919010509
neutralizing antibody fails to impact the course of ebola virus infection in monkeys.prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. in this study, we have investigated the ability of the neutralizing human monoclonal antibody, kz52, to protect against ebola virus in rhesus macaques. this antibody was previously shown to fully protect guinea pigs from infection. four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody kz52 intravenously 1 d before challenge with ...200717238286
a paramyxovirus-vectored intranasal vaccine against ebola virus is immunogenic in vector-immune animals.ebola virus (ebov) causes outbreaks of a highly lethal hemorrhagic fever in humans. the virus can be transmitted by direct contact as well as by aerosol and is considered a potential bioweapon. because direct immunization of the respiratory tract should be particularly effective against infection of mucosal surfaces, we previously developed an intranasal vaccine based on replication-competent human parainfluenza virus type 3 (hpiv3) expressing ebov glycoprotein gp (hpiv3/ebogp) and showed that i ...200818570964
mutations abrogating vp35 interaction with double-stranded rna render ebola virus avirulent in guinea pigs.ebola virus (ebov) protein vp35 is a double-stranded rna (dsrna) binding inhibitor of host interferon (ifn)-alpha/beta responses that also functions as a viral polymerase cofactor. recent structural studies identified key features, including a central basic patch, required for vp35 dsrna binding activity. to address the functional significance of these vp35 structural features for ebov replication and pathogenesis, two point mutations, k319a/r322a, that abrogate vp35 dsrna binding activity and s ...201020071589
postexposure protection of non-human primates against a lethal ebola virus challenge with rna interference: a proof-of-concept study.we previously showed that small interfering rnas (sirnas) targeting the zaire ebola virus (zebov) rna polymerase l protein formulated in stable nucleic acid-lipid particles (snalps) completely protected guineapigs when administered shortly after a lethal zebov challenge. although rodent models of zebov infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. we therefore assessed the ...201020511019
use of the syrian hamster as a new model of ebola virus disease and other viral hemorrhagic fevers.historically, mice and guinea pigs have been the rodent models of choice for therapeutic and prophylactic countermeasure testing against ebola virus disease (evd). recently, hamsters have emerged as a novel animal model for the in vivo study of evd. in this review, we discuss the history of the hamster as a research laboratory animal, as well as current benefits and challenges of this model. availability of immunological reagents is addressed. salient features of evd in hamsters, including relev ...201223242370
disease modeling for ebola and marburg viruses.the filoviruses ebola and marburg are zoonotic agents that are classified as both biosafety level 4 and category a list pathogens. these viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in central africa. their natural reservoir has not been definitely identified, but certain species of african bat have been associated with ebola and marburg infections. currently, there are no licensed options available for either treatment or prophyl ...200919132113
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
[antigenic differences in wild-type and guinea pig-adapted ebola virus strains].the splenocytes isolated from the mice immunized with wild-type or guinea pig-adapted ebola virus strains were used to obtain hybridoma collections. investigation of the monoclonal antibodies (mab) obtained to one of the strains to another revealed antigenic interstrain differences in nucleoprotein and vp40. it is interesting that the differences were found in the hydridoma collection obtained against the wild-type strain. the mabs produced by hydridomas to the adapted strain were found to equal ...201021381339
protective efficacy of neutralizing antibodies against ebola virus infection.ebola virus causes lethal hemorrhagic fever in humans and nonhuman primates, but no effective antiviral compounds are available for the treatment of this infection. the surface glycoprotein (gp) of ebola virus is an important target of neutralizing antibodies. although passive transfer of gp-specific antibodies has been evaluated in mouse and guinea pig models, protection was achieved only by treatment shortly before or after virus challenge. using these animal models, we evaluated the protectiv ...200717055127
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
kunjin virus replicon-based vaccines expressing ebola virus glycoprotein gp protect the guinea pig against lethal ebola virus infection.pre- or postexposure treatments against the filoviral hemorrhagic fevers are currently not available for human use. we evaluated, in a guinea pig model, the immunogenic potential of kunjin virus (kun)-derived replicons as a vaccine candidate against ebola virus (ebov). virus like particles (vlps) containing kun replicons expressing ebov wild-type glycoprotein gp, membrane anchor-truncated gp (gp/ctr), and mutated gp (d637l) with enhanced shedding capacity were generated and assayed for their pro ...201121987742
inactivated vaccine for ebola virus efficacious in guineapig model. 19806108462
a single intranasal inoculation with a paramyxovirus-vectored vaccine protects guinea pigs against a lethal-dose ebola virus challenge.to determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against ebola virus (ev), recombinant human parainfluenza virus type 3 (hpiv3) was modified to express either the ev structural glycoprotein (gp) by itself (hpiv3/ebogp) or together with the ev nucleoprotein (np) (hpiv3/ebogp-np). expression of ev gp by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in vero cells. ...200616474134
postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by rna interference.ebola virus (ebov) infection causes a frequently fatal hemorrhagic fever (hf) that is refractory to treatment with currently available antiviral therapeutics. rna interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. here, we describe the development of a potential therapy for ebov infection that is based on small interfering rnas (sirnas).200616703508
vp24 is a molecular determinant of ebola virus virulence in guinea pigs.in sharp contrast to human and nonhuman primates, guinea pigs and some other mammals resist ebola virus (ebov) replication and do not develop illness upon virus inoculation. however, serial passaging of ebov in guinea pigs results in a selection of variants with high pathogenicity. in this report, using a reverse genetics approach, we demonstrate that this dramatic increase in ebov pathogenicity is associated with amino acid substitutions in the structural protein vp24. we show that although rep ...201121987737
chimpanzee adenovirus vaccine protects against zaire ebola virus.this study evaluated the use of a chimpanzee-based adenovirus vaccine in mouse and guinea pigs models of zaire ebola virus (zebov) infection. vaccine vector expressing the envelope glycoprotein of zebov was created from the molecular clone of chimpanzee adenovirus pan7 (adc7). adc7 vaccine stimulated robust t and b cell responses to zebov in naïve mice inducing complete protection to an otherwise lethal challenge of zebov. complete protection to zaire ebola virus was also observed in guinea pigs ...200616356525
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
mouse models for filovirus infections.the filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (hf) in humans and nonhuman primates. because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral hf, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (nhps), guinea pigs and mice as animal models. nhps appear to closely mirror filoviral ...201223170168
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
complex adenovirus-vectored vaccine protects guinea pigs from three strains of marburg virus challenges.the marburg virus (marv), an african filovirus closely related to the ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of marv infections. in order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cadvax) to overexpress a marv glycoprotein (gp) fusion protein derived ...200616820184
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
minimal in vivo efficacy of iminosugars in a lethal ebola virus guinea pig model.the antiviral properties of iminosugars have been reported previously in vitro and in small animal models against ebola virus (ebov); however, their effects have not been tested in larger animal models such as guinea pigs. we tested the iminosugars n-butyl-deoxynojirimycin (nb-dnj) and n-(9-methoxynonyl)-1deoxynojirimycin (mon-dnj) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted ebov. 1850 mg/kg/day nb-dnj and 120 mg/kg/da ...201627880800
evaluation of the activity of lamivudine and zidovudine against ebola virus.in the fall of 2014, an international news agency reported that patients suffering from ebola virus disease (evd) in liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis b virus infections. according to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from ebola virus disease. in this study, the anti-ebola virus (ebov) activity of lamivudine and another antiretroviral, zidovudine, ...201627902714
animal models for ebola and marburg virus infections.ebola and marburg hemorrhagic fevers (ehf and mhf) are caused by the filoviridae family, ebolavirus and marburgvirus (ebolavirus and marburgvirus), respectively. these severe diseases have high mortality rates in humans. although ehf and mhf are endemic to sub-saharan africa. a novel filovirus, lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in spain where filoviral hemorrhagic fever had never been reported. the virulence of this virus has no ...201324046765
production, purification and immunogenicity of recombinant ebola virus proteins - a comparison of freund's adjuvant and adjuvant system 03.there is an urgent need for ebola virus (ebov) proteins, ebov-specific antibodies and recombinant antigens to be used in diagnostics and as potential vaccine candidates. our objective was to produce and purify recombinant proteins for immunological assays and for the production of polyclonal ebov specific antibodies. in addition, a limited comparison of the adjuvant effects of freund's complete adjuvant (fca) and adjuvant system 03 (as03) was carried out. recombinant ebov gst-vp24, -vp30, -vp35, ...201728025125
antiviral screening of multiple compounds against ebola virus.in light of the recent outbreak of ebola virus (ebov) disease in west africa, there have been renewed efforts to search for effective antiviral countermeasures. a range of compounds currently available with broad antimicrobial activity have been tested for activity against ebov. using live ebov, eighteen candidate compounds were screened for antiviral activity in vitro. the compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to dis ...201627801778
anti-ebov gp iggs lacking α1-3-galactose and neu5gc prolong survival and decrease blood viral load in ebov-infected guinea pigs.polyclonal xenogenic iggs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as ebola hemorrhagic fever. igg glycans display powerful xenogeneic antigens in humans, for example α1-3 galactose and the glycolyl form of neuraminic acid neu5gc, and iggs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. in this paper, we explored whether low immuno ...201627280712
ebolavirus glycoprotein fc fusion protein protects guinea pigs against lethal challenge.ebola virus (ebov), a member of the filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. currently, there are no licensed vaccines or therapeutics to prevent and treat ebov infection. several vaccines based on the ebov glycoprotein (gp) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. we previously demonstrated that a subunit vaccine containing the extracellular do ...201627622456
an adenovirus vaccine expressing ebola virus variant makona glycoprotein is efficacious in guinea pigs and nonhuman primates.a licensed vaccine against ebola virus (ebov) remains unavailable, despite >11 000 deaths from the 2014-2016 outbreak of ebov disease in west africa. past studies have shown that recombinant vaccine viruses expressing ebov glycoprotein (gp) are able to protect nonhuman primates (nhps) from a lethal ebov challenge. however, these vaccines express the viral gp-based ebov variants found in central africa, which has 97.3% amino acid homology to the makona variant found in west africa. our previous s ...201627493239
post-exposure treatment of ebola virus disease in guinea pigs using ebotab, an ovine antibody-based therapeutic.ebola virus (ebov) is highly pathogenic, with a predisposition to cause outbreaks in human populations accompanied by significant mortality. an ovine polyclonal antibody therapy has been developed against ebov, named ebotab. when tested in the stringent guinea pig model of ebov disease, ebotab has been shown to confer protection at levels of 83.3%, 50% and 33.3% when treatment was first started on days 3, 4 and 5 post-challenge, respectively. these timepoints of when ebotab treatment was initiat ...201627465308
rodent-adapted filoviruses and the molecular basis of pathogenesis.ebola, marburg, and ravn viruses, all filoviruses, are the causative agents of severe hemorrhagic fever. much of what we understand about the pathogenesis of filovirus disease is derived from work with animal models, including nonhuman primates, which are considered the "gold standard" filovirus model since they faithfully recapitulate the clinical hallmarks of filovirus disease. however, rodent models, including the mouse, guinea pig, and hamster, also exist for ebola, marburg, and ravn viruses ...201627189922
single-vector, single-injection recombinant vesicular stomatitis virus vaccines against high-containment viruses.there are many avenues for making an effective vaccine against viruses. depending on the virus these can include one of the following: inactivation of whole virions; attenuation of viruses; recombinant viral proteins; non-replication-competent virus particles; or surrogate virus vector systems such as vesicular stomatitis virus (vsv). vsv is a prototypic enveloped animal virus that has been used for over four decades to study virus replication, entry, and assembly due to its ability to replicate ...201627076138
adapted lethality: what we can learn from guinea pig-adapted ebola virus infection model.establishment of small animal models of ebola virus (ebov) infection is important both for the study of genetic determinants involved in the complex pathology of ebov disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. since the wild-type ebov is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. here, we provi ...201626989413
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
role of ebola virus vp24 protein in inhibition of interferonogenesis.the effects of recombinant analog of natural ebola virus protein vp24 in configurations virulent (vp24-ad) and avirulent (vp24-w) for guinea pigs on interferonogenesis were studied in vivo and in vitro. amino acid differences were determined by his186 substitution in avirulent (nonlethal) configuration for tyr in the virulent (lethal) one. recombinant analogs vp24-w and vp24-ad inhibited interferonogenesis in vivo and in vitro. inhibition by the two protein configurations was virtually the same.201626750927
development of a cost-effective ovine polyclonal antibody-based product, ebotab, to treat ebola virus infection.the highly glycosylated glycoprotein spike of ebola virus (ebov-gp1,2) is the primary target of the humoral host response. recombinant ebov-gp ectodomain (ebov-gp1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized ebov. a pool of intact ovine immunoglobulin g, herein termed ebotab, ...201626715676
evaluation of different strategies for post-exposure treatment of ebola virus infection in rodents.zaire ebola virus (zebov) is a pathogen that causes severe hemorrhagic fever in humans and non-human primates. there are currently no licensed vaccines or approved treatments available against zebov infections. the goal of this work was to evaluate different treatment strategies in conjunction with a replication deficient, recombinant human adenovirus serotype 5-based vaccine expressing the zaire ebola virus glycoprotein (ad-cagoptzgp) in ebola infected mice and guinea pigs.guinea pigs were trea ...201123205319
discovery and early development of avi-7537 and avi-7288 for the treatment of ebola virus and marburg virus infections.there are no currently approved treatments for filovirus infections. in this study we report the discovery process which led to the development of antisense phosphorodiamidate morpholino oligomers (pmos) avi-6002 (composed of avi-7357 and avi-7539) and avi-6003 (composed of avi-7287 and avi-7288) targeting ebola virus and marburg virus respectively. the discovery process involved identification of optimal transcript binding sites for pmo based rna-therapeutics followed by screening for effective ...201223202506
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( ...201526491156
genomic rna editing and its impact on ebola virus adaptation during serial passages in cell culture and infection of guinea pigs.synthesis of the structural, surface glycoprotein (gp) of ebola virus (ebov) is dependent on transcriptional rna editing phenomenon. editing results in the insertion of an extra adenosine by viral polymerase at the editing site (7 consecutive template uridines) during transcription of gp gene of the wild-type virus (ebov/7u). in this study, we demonstrate that passage of ebov/7u in vero e6 cells results in the appearance and rapid accumulation of a variant (ebov/8u) containing an additional urid ...201121987773
rna editing of the gp gene of ebola virus is an important pathogenicity factor.synthesis of the surface glycoprotein gp of ebola virus (ebov) is dependent on transcriptional rna editing, whereas direct expression of the gp gene results in synthesis of nonstructural secreted glycoprotein sgp. in this study, we investigate the role of rna editing in the pathogenicity of ebov using a guinea pig model and recombinant guinea pig-adapted ebov containing mutations at the editing site, allowing expression of surface gp without the need for rna editing, and also preventing synthesi ...201526138826
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
vaccination with a highly attenuated recombinant vesicular stomatitis virus vector protects against challenge with a lethal dose of ebola virus.previously, recombinant vesicular stomatitis virus (rvsv) pseudotypes expressing ebolavirus glycoproteins (gps) in place of the vsv g protein demonstrated protection of nonhuman primates from lethal homologous ebolavirus challenge. those pseudotype vectors contained no additional attenuating mutations in the rvsv genome. here we describe rvsv vectors containing a full complement of vsv genes and expressing the ebola virus (ebov) gp from an additional transcription unit. these rvsv vectors contai ...201526109675
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
a single sublingual dose of an adenovirus-based vaccine protects against lethal ebola challenge in mice and guinea pigs.sublingual (sl) delivery, a noninvasive immunization method that bypasses the intestinal tract for direct entry into the circulation, was evaluated with an adenovirus (ad5)-based vaccine for ebola. mice and guinea pigs were immunized via the intramuscular (im), nasal (in), oral (po) and sl routes. sl immunization elicited strong transgene expression in and attracted cd11c(+) antigen presenting cells to the mucosa. a sl dose of 1 × 10(8) infectious particles induced ebola zaire glycoprotein (zgp) ...201122149096
mechanisms of immunity in post-exposure vaccination against ebola virus infection.ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. although there is no clinically proven vaccine or treatment for ebola virus infection, a virus-like particle (vlp) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. in this work, we report that vlps protect ebola virus-infected mice when given 24 hours post-infection. analysis of cytokine expression in se ...201525785602
soluble glycoprotein is not required for ebola virus virulence in guinea pigs.ebola virus (ebov) uses transcriptional editing to express several glycoproteins (gps), including secreted soluble gp (sgp) and structural gp1,2, from a single gene. recombinant viruses predominantly expressing gp1,2 are known to rapidly mutate and acquire an editing site predominantly expressing sgp in vivo, suggesting an important role of this protein during infection. therefore, we generated a recombinant virus that is no longer able to express sgp and assessed its virulence in the ebov guine ...201525957965
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
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
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
elucidating variations in the nucleotide sequence of ebola virus associated with increasing pathogenicity.ebolaviruses causes a severe and often fatal hemorrhagic fever in humans, with some species such as ebola virus having case fatality rates approaching 90%. currently the worst ebola virus outbreak since the disease was discovered is occurring in west africa. although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, ebola virus variants could be selected which are better adapted for human-to-human transmission.201425416632
ebola virus transmission in guinea pigs.ebola virus (ebov) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. to establish an ebov transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (ld50) of gp-adapted ebov, a ...201525392221
mission critical: mobilization of essential animal models for ebola, nipah, and machupo virus infections.the reports for ebola virus zaire (ebov), nipah virus, and machupo virus (macv) pathogenesis, in this issue of veterinary pathology, are timely considering recent events, both nationally and internationally. ebov, nipah virus, and macv cause highly lethal infections for which no food and drug administration (fda) licensed vaccines or therapies exist. not only are there concerns that these agents could be used by those with malicious intent, but shifts in ecological distribution of viral reservoi ...201525352204
immunization with vesicular stomatitis virus vaccine expressing the ebola glycoprotein provides sustained long-term protection in rodents.ebola virus (ebov) infections cause lethal hemorrhagic fever in humans, resulting in up to 90% mortality. ebov outbreaks are sporadic and unpredictable in nature; therefore, a vaccine that is able to provide durable immunity is needed to protect those who are at risk of exposure to the virus. this study assesses the long-term efficacy of the vesicular stomatitis virus (vsv)-based vaccine (vsvδg/ebovgp) in two rodent models of ebov infection. mice and guinea pigs were first immunized with 2×10(4) ...201425173474
development of a murine model for aerosolized ebolavirus infection using a panel of recombinant inbred mice.countering aerosolized filovirus infection is a major priority of biodefense research. aerosol models of filovirus infection have been developed in knock-out mice, guinea pigs and non-human primates; however, filovirus infection of immunocompetent mice by the aerosol route has not been reported. a murine model of aerosolized filovirus infection in mice should be useful for screening vaccine candidates and therapies. in this study, various strains of wild-type and immunocompromised mice were expo ...201223207275
catheterized guinea pigs infected with ebola zaire virus allows safer sequential sampling to determine the pharmacokinetic profile of a phosphatidylserine-targeting monoclonal antibody.sequential sampling from animals challenged with highly pathogenic organisms, such as haemorrhagic fever viruses, is required for many pharmaceutical studies. using the guinea pig model of ebola virus infection, a catheterized system was used which had the benefits of allowing repeated sampling of the same cohort of animals, and also a reduction in the use of sharps at high biological containment. levels of a ps-targeting antibody (bavituximab) were measured in ebola-infected animals and uninfec ...201323165089
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