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Heinz Feldmann - One of the best experts on this subject based on the ideXlab platform.
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Neutralizing Monoclonal Antibodies Against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect From Virus Challenge in a Preclinical Hamster Model
2020Co-Authors: James Duehr, Meagan Mcmahon, Brandi N. Williamson, Fatima Amanat, Alan Durbin, David W. Hawman, Danny Noack, Skyler Uhl, Gene S. Tan, Heinz FeldmannAbstract:ABSTRACT Hantaviruses are the etiological agent of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The latter is associated with case fatality rates ranging from 30% to 50%. HCPS cases are rare, with approximately 300 recorded annually in the Americas. Recently, an HCPS outbreak of unprecedented size has been occurring in and around Epuyen, in the southwestern Argentinian state of Chubut. Since November of 2018, at least 29 cases have been laboratory confirmed, and human-to-human transmission is suspected. Despite posing a significant threat to public health, no treatment or vaccine is available for hantaviral disease. Here, we describe an effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) of Andes virus (ANDV), the causative agent of the Epuyen outbreak. Using murine hybridoma technology, we generated 19 distinct monoclonal antibodies (MAbs) against ANDV GnGc. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes glycoprotein (GP) (VSV-ANDV), 12 MAbs showed potent neutralization and 8 showed activity in an antibody-dependent cellular cytotoxicity reporter assay. Escape mutant analysis revealed that neutralizing MAbs targeted both the Gn and the Gc. Four MAbs that bound different epitopes were selected for preclinical studies and were found to be 100% protective against lethality in a Syrian Hamster Model of ANDV infection. These data suggest the existence of a wide array of neutralizing antibody epitopes on hantavirus GnGc with unique properties and mechanisms of action. IMPORTANCE Infections with New World hantaviruses are associated with high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of the hantaviral GnGc complex, its antigenicity, and its fusion machinery are poorly understood. Protective monoclonal antibodies against GnGc have the potential to be developed into therapeutics against hantaviral disease and are also great tools to elucidate the biology of the glycoprotein complex.
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Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model
2020Co-Authors: James Duehr, Meagan Mcmahon, Fatima Amanat, Alan Durbin, David W. Hawman, Danny Noack, Skyler Uhl, Gene S. Tan, Brandi Williamson, Heinz FeldmannAbstract:Infections with New World hantaviruses are associated with high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of the hantaviral GnGc complex, its antigenicity, and its fusion machinery are poorly understood. Protective monoclonal antibodies against GnGc have the potential to be developed into therapeutics against hantaviral disease and are also great tools to elucidate the biology of the glycoprotein complex.Hantaviruses are the etiological agent of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The latter is associated with case fatality rates ranging from 30% to 50%. HCPS cases are rare, with approximately 300 recorded annually in the Americas. Recently, an HCPS outbreak of unprecedented size has been occurring in and around Epuyén, in the southwestern Argentinian state of Chubut. Since November of 2018, at least 29 cases have been laboratory confirmed, and human-to-human transmission is suspected. Despite posing a significant threat to public health, no treatment or vaccine is available for hantaviral disease. Here, we describe an effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) of Andes virus (ANDV), the causative agent of the Epuyén outbreak. Using murine hybridoma technology, we generated 19 distinct monoclonal antibodies (MAbs) against ANDV GnGc. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes glycoprotein (GP) (VSV-ANDV), 12 MAbs showed potent neutralization and 8 showed activity in an antibody-dependent cellular cytotoxicity reporter assay. Escape mutant analysis revealed that neutralizing MAbs targeted both the Gn and the Gc. Four MAbs that bound different epitopes were selected for preclinical studies and were found to be 100% protective against lethality in a Syrian Hamster Model of ANDV infection. These data suggest the existence of a wide array of neutralizing antibody epitopes on hantavirus GnGc with unique properties and mechanisms of action
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a Hamster Model for marburg virus infection accurately recapitulates marburg hemorrhagic fever
2016Co-Authors: Andrea Marzi, Elaine Haddock, Dana P. Scott, Heinz Feldmann, Logan Banadyga, Tina Thomas, Kui Shen, Eva Horne, Hideki EbiharaAbstract:Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal Models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden Hamster Model of MHF using a Hamster-adapted MARV variant Angola. Remarkably, this Model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF Hamster Model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.
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A Hamster Model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever
2016Co-Authors: Andrea Marzi, Elaine Haddock, Dana P. Scott, Heinz Feldmann, Logan Banadyga, Tina Thomas, Kui Shen, Eva J. Horne, Hideki EbiharaAbstract:Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal Models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden Hamster Model of MHF using a Hamster-adapted MARV variant Angola. Remarkably, this Model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF Hamster Model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.
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Protective Efficacy of a Bivalent Recombinant Vesicular Stomatitis Virus Vaccine in the Syrian Hamster Model of Lethal Ebola Virus Infection
2016Co-Authors: Heinz FeldmannAbstract:Background. Outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central Africa and overlap with the occurrence of other infectious diseases of public health importance. Methods. As a proof of concept we developed a bivalent recombinant vaccine based on vesicular stomatitis virus (VSV) expressing the Zaire ebolavirus (ZEBOV) and Andes virus (ANDV) glycoproteins (VSVDG/Dual) and evaluated its protective efficacy in the common lethal Syrian Hamster Model. Hamsters were vaccinated with VSVDG/Dual and were lethally challenged with ZEBOV or ANDV. Time to immunity and postexposure treatment were evaluated by immunizing Hamsters at different times prior to and post ZEBOV challenge. Results. A single immunization with VSVDG/Dual conferred complete and sterile protection against lethal ZEBOV and ANDV challenge. Complete protection was achieved with an immunization as close as 3 days prior to ZEBOV challenge, and 40 % of the animals were even protected when treated with VSVDG/Dual one day postchallenge. In comparison to the monovalent VSV vaccine, the bivalent vaccine has slightly reduced postexposure efficacy most likely due to its restricted lymphoid organ replication. Conclusions. Bivalent VSV vectors are a feasible approach to vaccination against multiple pathogens. Members of the genera Ebolavirus (EBOV) and Mar-burgvirus (MARV), family Filoviridae, are responsibl
Everton Fagonde Da Silva - One of the best experts on this subject based on the ideXlab platform.
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Genome of Leptospira borgpetersenii strain 4E, a highly virulent isolate obtained from Mus musculus in southern Brazil
2017Co-Authors: Marcus Redü Eslabão, Everton Fagonde Da Silva, Frederico Schmitt Kremer, Rommel Thiago Juca Ramos, Artur Luiz Da Costa Da Silva, Vasco Ariston De Carvalho Azevedo, Luciano Da Silva Pinto, Odir Antonio DellagostinAbstract:A previous study by our group reported the isolation and characterisation of Leptospira borgpetersenii serogroup Ballum strain 4E. This strain is of particular interest because it is highly virulent in the Hamster Model. In this study, we performed whole-genome shotgun genome sequencing of the strain using the SOLiD sequencing platform. By assembling and analysing the new genome, we were able to identify novel features that have been previously overlooked in genome annotations of other strains belonging to the same species.
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highly virulent leptospira borgpetersenii strain characterized in the Hamster Model
2011Co-Authors: Juliana Alcoforado Diniz, Samuel Rodrigues Felix, Josiane Bonelraposo, Amilton Clair Pinto Seixas Neto, Flavia Aleixo Vasconcellos, Andre Alex Grassmann, Odir Antonio Dellagostin, Jose Antonio Guimaraes Aleixo, Everton Fagonde Da SilvaAbstract:Abstract. A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian Hamsters (Mesocricetus auratus) and carried out standardization of lethal dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced lethality in the Hamster Model with inocula lower than 10 leptospires, and histopathological examination of animals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages (P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.
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short report highly virulent leptospira borgpetersenii strain characterized in the Hamster Model
2011Co-Authors: Juliana Alcoforado Diniz, Samuel Rodrigues Felix, Josiane Bonelraposo, Flavia Aleixo Vasconcellos, Andre Alex Grassmann, Odir Antonio Dellagostin, Jose Antonio Guimaraes Aleixo, Everton Fagonde Da SilvaAbstract:Both man and animal become accidental hosts through exposure to chroni- cally infected animals, mostly rodents, that shed leptospires in their urine. 2 This zoonosis is characterized by a broad spec- trum of clinical manifestations, ranging from subclinical infec- tion to Weil's syndrome 3 and severe pulmonary hemorrhage syndrome. 4 Abstract. A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian Hamsters ( Mesocricetus auratus ) and carried out standardization of lethal dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced lethality in the Hamster Model with inocula lower than 10 leptospires, and histopathological examination of ani- mals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages ( P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.
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characterization of virulence of leptospira isolates in a Hamster Model
2008Co-Authors: Everton Fagonde Da Silva, Cleiton S. Santos, Daniel A. Athanazio, Mitermayer G. Reis, Nubia Seyffert, Fabiana Kommling Seixas, Gustavo C Cerqueira, Michel Quevedo Fagundes, Claudiomar Soares Brod, Odir Antonio DellagostinAbstract:Effort has been made to identify protective antigens in order to develop a recombinant vaccine against leptospirosis. Several attempts failed to conclusively demonstrate efficacy of vaccine candidates due to the lack of an appropriate Model of lethal leptospirosis. The purposes of our study were: (i) to test the virulence of leptospiral isolates from Brazil, which are representative of important serogroups that cause disease in humans and animals; and (ii) to standardize the lethal dose 50% (LD(50)) for each of the virulent strains using a Hamster (Mesocricetus auratus) Model. Five of seven Brazilian isolates induced lethality in a Hamster Model, with inocula lower than 200 leptospires. Histopathological examination of infected animals showed typical lesions found in both natural and experimental leptospirosis. Results described here demonstrated the potential use of Brazilian isolates as highly virulent strains in challenge experiments using Hamster as an appropriate animal Model for leptospirosis. Furthermore these strains may be useful in heterologous challenge studies which aim to evaluate cross-protective responses induced by sub-unit vaccine candidates.
Jasper F W Chan - One of the best experts on this subject based on the ideXlab platform.
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surgical mask partition reduces the risk of noncontact transmission in a golden syrian Hamster Model for coronavirus disease 2019 covid 19
2020Co-Authors: Jasper F W Chan, Shuofeng Yuan, Anna Jinxia Zhang, Vincent Kwokman Poon, Chris Chungsing Chan, Andrew C Y Lee, Zhimeng Fan, Ronghui LiangAbstract:Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium- to large-sized respiratory droplets, although airborne transmission may be possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19. Methods We used a well-established golden Syrian Hamster SARS-CoV-2 Model. We placed SARS-CoV-2-challenged index Hamsters and naive Hamsters into closed system units each comprising 2 different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed between the cages was investigated. Besides clinical scoring, Hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression. Results Noncontact transmission was found in 66.7% (10/15) of exposed naive Hamsters. Surgical mask partition for challenged index or naive Hamsters significantly reduced transmission to 25% (6/24, P = .018). Surgical mask partition for challenged index Hamsters significantly reduced transmission to only 16.7% (2/12, P = .019) of exposed naive Hamsters. Unlike the severe manifestations of challenged Hamsters, infected naive Hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues. Conclusions SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei which could be reduced by surgical mask partition in the Hamster Model. This is the first in vivo experimental evidence to support the possible benefit of surgical mask in prevention of COVID-19 transmission, especially when masks were worn by infected individuals.
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simulation of the clinical and pathological manifestations of coronavirus disease 2019 covid 19 in golden syrian Hamster Model implications for disease pathogenesis and transmissibility
2020Co-Authors: Jasper F W Chan, Shuofeng Yuan, Anna Jinxia Zhang, Vincent Kwokman Poon, Chris Chungsing Chan, Andrew C Y Lee, Wan Mui Chan, Zhimeng FanAbstract:Background A physiological small-animal Model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian Hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis studies were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titer, chemokine/cytokine level, and neutralizing antibody titer. Results The Syrian Hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with viral nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked chemokine/cytokine activation were observed within the first week of virus challenge. The mean lung virus titer was between 105 and 107 TCID50/g. Challenged index Hamsters consistently infected naive contact Hamsters housed within the same cages, resulting in similar pathology but not weight loss. All infected Hamsters recovered and developed mean serum neutralizing antibody titers ≥1:427 14 days postchallenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent nonsynonymous adaptive mutation of the spike was found in viruses isolated from the infected Hamsters. Conclusions Besides satisfying Koch's postulates, this readily available Hamster Model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.
Odir Antonio Dellagostin - One of the best experts on this subject based on the ideXlab platform.
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Genome of Leptospira borgpetersenii strain 4E, a highly virulent isolate obtained from Mus musculus in southern Brazil
2017Co-Authors: Marcus Redü Eslabão, Everton Fagonde Da Silva, Frederico Schmitt Kremer, Rommel Thiago Juca Ramos, Artur Luiz Da Costa Da Silva, Vasco Ariston De Carvalho Azevedo, Luciano Da Silva Pinto, Odir Antonio DellagostinAbstract:A previous study by our group reported the isolation and characterisation of Leptospira borgpetersenii serogroup Ballum strain 4E. This strain is of particular interest because it is highly virulent in the Hamster Model. In this study, we performed whole-genome shotgun genome sequencing of the strain using the SOLiD sequencing platform. By assembling and analysing the new genome, we were able to identify novel features that have been previously overlooked in genome annotations of other strains belonging to the same species.
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highly virulent leptospira borgpetersenii strain characterized in the Hamster Model
2011Co-Authors: Juliana Alcoforado Diniz, Samuel Rodrigues Felix, Josiane Bonelraposo, Amilton Clair Pinto Seixas Neto, Flavia Aleixo Vasconcellos, Andre Alex Grassmann, Odir Antonio Dellagostin, Jose Antonio Guimaraes Aleixo, Everton Fagonde Da SilvaAbstract:Abstract. A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian Hamsters (Mesocricetus auratus) and carried out standardization of lethal dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced lethality in the Hamster Model with inocula lower than 10 leptospires, and histopathological examination of animals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages (P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.
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short report highly virulent leptospira borgpetersenii strain characterized in the Hamster Model
2011Co-Authors: Juliana Alcoforado Diniz, Samuel Rodrigues Felix, Josiane Bonelraposo, Flavia Aleixo Vasconcellos, Andre Alex Grassmann, Odir Antonio Dellagostin, Jose Antonio Guimaraes Aleixo, Everton Fagonde Da SilvaAbstract:Both man and animal become accidental hosts through exposure to chroni- cally infected animals, mostly rodents, that shed leptospires in their urine. 2 This zoonosis is characterized by a broad spec- trum of clinical manifestations, ranging from subclinical infec- tion to Weil's syndrome 3 and severe pulmonary hemorrhage syndrome. 4 Abstract. A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian Hamsters ( Mesocricetus auratus ) and carried out standardization of lethal dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced lethality in the Hamster Model with inocula lower than 10 leptospires, and histopathological examination of ani- mals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages ( P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.
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characterization of virulence of leptospira isolates in a Hamster Model
2008Co-Authors: Everton Fagonde Da Silva, Cleiton S. Santos, Daniel A. Athanazio, Mitermayer G. Reis, Nubia Seyffert, Fabiana Kommling Seixas, Gustavo C Cerqueira, Michel Quevedo Fagundes, Claudiomar Soares Brod, Odir Antonio DellagostinAbstract:Effort has been made to identify protective antigens in order to develop a recombinant vaccine against leptospirosis. Several attempts failed to conclusively demonstrate efficacy of vaccine candidates due to the lack of an appropriate Model of lethal leptospirosis. The purposes of our study were: (i) to test the virulence of leptospiral isolates from Brazil, which are representative of important serogroups that cause disease in humans and animals; and (ii) to standardize the lethal dose 50% (LD(50)) for each of the virulent strains using a Hamster (Mesocricetus auratus) Model. Five of seven Brazilian isolates induced lethality in a Hamster Model, with inocula lower than 200 leptospires. Histopathological examination of infected animals showed typical lesions found in both natural and experimental leptospirosis. Results described here demonstrated the potential use of Brazilian isolates as highly virulent strains in challenge experiments using Hamster as an appropriate animal Model for leptospirosis. Furthermore these strains may be useful in heterologous challenge studies which aim to evaluate cross-protective responses induced by sub-unit vaccine candidates.
Hideki Ebihara - One of the best experts on this subject based on the ideXlab platform.
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a Hamster Model for marburg virus infection accurately recapitulates marburg hemorrhagic fever
2016Co-Authors: Andrea Marzi, Elaine Haddock, Dana P. Scott, Heinz Feldmann, Logan Banadyga, Tina Thomas, Kui Shen, Eva Horne, Hideki EbiharaAbstract:Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal Models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden Hamster Model of MHF using a Hamster-adapted MARV variant Angola. Remarkably, this Model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF Hamster Model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.
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A Hamster Model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever
2016Co-Authors: Andrea Marzi, Elaine Haddock, Dana P. Scott, Heinz Feldmann, Logan Banadyga, Tina Thomas, Kui Shen, Eva J. Horne, Hideki EbiharaAbstract:Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal Models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden Hamster Model of MHF using a Hamster-adapted MARV variant Angola. Remarkably, this Model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF Hamster Model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.
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A Syrian Golden Hamster Model Recapitulating Ebola Hemorrhagic Fever
2012Co-Authors: Hideki Ebihara, Elaine Haddock, Marko Zivcec, Donald J. Gardner, Darryl Falzarano, Rachel Lacasse, Rebecca Rosenke, Dan Long, Elizabeth R. Fischer, Yoshihiro KawaokaAbstract:Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) Model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent Models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent Models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian Hamster Model of EHF using mouse-adapted Ebola virus. Infected Hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the Hamster seems to be superior to the existing rodent Models, offering a better tool for understanding the critical processes in pathogenesis and providing a new Model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.
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The Syrian Hamster Model of hantavirus pulmonary syndrome.
2012Co-Authors: David Safronetz, Hideki Ebihara, Heinz FeldmannAbstract:Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal Model. To date, the only animal Model that resembles HPS in humans is the Syrian Hamster Model. Following infection with Andes virus, Hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in Hamsters. The last several years has seen an increase in studies utilizing the Andes virus Hamster Model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian Hamsters and discuss the suitability of utilizing this Model to evaluate potential medical countermeasures against HPS.
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Protective Efficacy of a Bivalent Recombinant Vesicular Stomatitis Virus Vaccine in the Syrian Hamster Model of Lethal Ebola Virus Infection
2011Co-Authors: Yoshimi Tsuda, Hideki Ebihara, David Safronetz, Rachel Lacasse, Andrea Marzi, Kyle E. Brown, Heinz FeldmannAbstract:Background. Outbreaks of filoviral hemorrhagic fever occur sporadically and unpredictably across wide regions in central Africa and overlap with the occurrence of other infectious diseases of public health importance. Methods. As a proof of concept we developed a bivalent recombinant vaccine based on vesicular stomatitis virus (VSV) expressing the Zaire ebolavirus (ZEBOV) and Andes virus (ANDV) glycoproteins (VSVDG/Dual) and evaluated its protective efficacy in the common lethal Syrian Hamster Model. Hamsters were vaccinated with VSVDG/Dual and were lethally challenged with ZEBOV or ANDV. Time to immunity and postexposure treatment were evaluated by immunizing Hamsters at different times prior to and post ZEBOV challenge. Results. A single immunization with VSVDG/Dual conferred complete and sterile protection against lethal ZEBOV and ANDV challenge. Complete protection was achieved with an immunization as close as 3 days prior to ZEBOV challenge, and 40% of the animals were even protected when treated with VSVDG/Dual one day postchallenge. In comparison to the monovalent VSV vaccine, the bivalent vaccine has slightly reduced postexposure efficacy most likely due to its restricted lymphoid organ replication. Conclusions. Bivalent VSV vectors are a feasible approach to vaccination against multiple pathogens. Members of the genera Ebolavirus (EBOV) and Marburgvirus (MARV), family Filoviridae, are responsible
