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Article ; Online: Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route.

Johnston, Sara C / Wilhelmsen, Catherine L / Shamblin, Joshua / Kimmel, Adrienne / Zelko, Justine / Wollen, Suzanne / Goff, Arthur J

Frontiers in immunology

2021 Volume 12, Page(s) 709772

Abstract: Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the ... ...

Abstract	Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for efficacy evaluations. The most commonly used nonhuman primate models for efficacy evaluations against Ebola virus utilize the intramuscular or aerosol route of exposure. Although clinical disease signs are similar to human cases, disease progression in these models is much more rapid, and this can pose significant hurdles for countermeasure evaluations. The objective of the present study was to evaluate the Ebola virus disease course that arises after cynomolgus macaques are exposed to Ebola virus by a mucosal route (the intranasal route). Two different doses (10 pfu and 100 pfu) and delivery methodologies (drop-wise and mucosal atomization device) were evaluated on this study. Differences in clinical disease between dose and delivery groups were not noted. However, a delayed disease course was identified for approximately half of the animals on study, and this delayed disease was dose and administration method independent. Therefore, it appears that mucosal exposure with Ebola virus results in a disease course in cynomolgus macaques that more accurately replicates that which is documented for human cases. In summary, the data presented support the need for further development of this model as a possible alternative to parenteral and small-particle aerosol models for the study of human Ebola virus disease and for countermeasure evaluations.
MeSH term(s)	Administration, Intranasal ; Amylases/metabolism ; Animals ; Disease Models, Animal ; Disease Progression ; Female ; Hemorrhagic Fever, Ebola/etiology ; Hemorrhagic Fever, Ebola/immunology ; Hemorrhagic Fever, Ebola/pathology ; Hemorrhagic Fever, Ebola/virology ; Macaca fascicularis ; Male ; RNA, Viral/blood
Chemical Substances	RNA, Viral ; Amylases (EC 3.2.1.-)
Language	English
Publishing date	2021-08-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.709772
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Article ; Online: Detailed analysis of the pathologic hallmarks of Nipah virus (Malaysia) disease in the African green monkey infected by the intratracheal route.

Cline, Curtis / Bell, Todd M / Facemire, Paul / Zeng, Xiankun / Briese, Thomas / Lipkin, W Ian / Shamblin, Joshua D / Esham, Heather L / Donnelly, Ginger C / Johnson, Joshua C / Hensley, Lisa E / Honko, Anna N / Johnston, Sara C

PloS one

2022 Volume 17, Issue 2, Page(s) e0263834

Abstract: Disease associated with Nipah virus infection causes a devastating and often fatal spectrum of syndromes predominated by both respiratory and neurologic conditions. Additionally, neurologic sequelae may manifest months to years later after virus exposure ...

Abstract	Disease associated with Nipah virus infection causes a devastating and often fatal spectrum of syndromes predominated by both respiratory and neurologic conditions. Additionally, neurologic sequelae may manifest months to years later after virus exposure or apparent recovery. In the two decades since this disease emerged, much work has been completed in an attempt to understand the pathogenesis and facilitate development of medical countermeasures. Here we provide detailed organ system-specific pathologic findings following exposure of four African green monkeys to 2.41×105 pfu of the Malaysian strain of Nipah virus. Our results further substantiate the African green monkey as a model of human Nipah virus disease, by demonstrating both the respiratory and neurologic components of disease. Additionally, we demonstrate that a chronic phase of disease exists in this model, that may provide an important opportunity to study the enigmatic late onset and relapse encephalitis as it is described in human disease.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Disease Models, Animal ; Encephalitis, Viral/pathology ; Henipavirus Infections/pathology ; Lung Diseases/pathology ; Lung Diseases/virology ; Malaysia ; Male ; Nipah Virus/classification ; Nipah Virus/pathogenicity
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0263834
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Article ; Online: Detection of Ebola Virus RNA Through Aerosol Sampling of Animal Biosafety Level 4 Rooms Housing Challenged Nonhuman Primates.

Harbourt, David E / Johnston, Sara C / Pettitt, James / Warren, Travis K / Dorman, William R

The Journal of infectious diseases

2017 Volume 215, Issue 4, Page(s) 554–558

Abstract: Ebola virus disease is a serious illness of humans and nonhuman primates (NHPs). Direct contact has been shown to be the primary source of Ebola (EBOV) transmission. We used a high-volume air sampler to determine whether EBOV could be detected during 3 ... ...

Abstract	Ebola virus disease is a serious illness of humans and nonhuman primates (NHPs). Direct contact has been shown to be the primary source of Ebola (EBOV) transmission. We used a high-volume air sampler to determine whether EBOV could be detected during 3 independent studies with EBOV-challenged NHPs. Viral RNA was recovered during days 9 and 10 of Study I and days 7 and 8 of Study III. Viral RNA levels were below limits of detection during all other collections. The results demonstrate that the biosafety level 4 (BSL-4) suit protects workers from aerosols in a BSL-4 environment using proper engineering and administrative controls.
MeSH term(s)	Aerosols/analysis ; Air Microbiology ; Animals ; Disease Models, Animal ; Disease Transmission, Infectious ; Ebolavirus/isolation & purification ; Hemorrhagic Fever, Ebola/virology ; Humans ; Limit of Detection ; Macaca fascicularis/virology ; Macaca mulatta/virology ; RNA, Viral/isolation & purification
Chemical Substances	Aerosols ; RNA, Viral
Language	English
Publishing date	2017--15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiw610
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Article ; Online: Vaccinia virus protein F12 associates with intracellular enveloped virions through an interaction with A36.

Johnston, Sara C / Ward, Brian M

Journal of virology

2008 Volume 83, Issue 4, Page(s) 1708–1717

Abstract: Vaccinia virus is the prototypical member of the family Poxviridae. Three morphologically distinct forms are produced during infection: intracellular mature virions (IMV), intracellular enveloped virions (IEV), and extracellular enveloped virions (EEV). ... ...

Abstract	Vaccinia virus is the prototypical member of the family Poxviridae. Three morphologically distinct forms are produced during infection: intracellular mature virions (IMV), intracellular enveloped virions (IEV), and extracellular enveloped virions (EEV). Two viral proteins, F12 and A36, are found exclusively on IEV but not on IMV and EEV. Analysis of membranes from infected cells showed that F12 was only associated with membranes and is not an integral membrane protein. A yeast two-hybrid assay revealed an interaction between amino acids 351 to 458 of F12 and amino acids 91 to 111 of A36. We generated a recombinant vaccinia virus that expresses an F12, which lacks residues 351 to 458. Characterization of this recombinant revealed a small-plaque phenotype and a subsequent defect in virus release similar to a recombinant virus that had F12L deleted. In addition, F12 lacking residues 351 to 458 was unable to associate with membranes in infected cells. These results suggest that F12 associates with IEV through an interaction with A36 and that this interaction is critical for the function of F12 during viral egress.
MeSH term(s)	Cell Line ; Cell Membrane/virology ; Gene Deletion ; Humans ; Protein Binding ; Protein Interaction Mapping ; Sequence Deletion ; Two-Hybrid System Techniques ; Vaccinia virus/physiology ; Viral Plaque Assay ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Viral Structural Proteins/metabolism ; Virus Assembly
Chemical Substances	A36R protein, Vaccinia virus ; F12L protein, Vaccinia virus ; Viral Proteins ; Viral Structural Proteins
Language	English
Publishing date	2008-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01364-08
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Article ; Online: Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques.

Downs, Isaac / Johnson, Joshua C / Rossi, Franco / Dyer, David / Saunders, David L / Twenhafel, Nancy A / Esham, Heather L / Pratt, William D / Trefry, John / Zumbrun, Elizabeth / Facemire, Paul R / Johnston, Sara C / Tompkins, Erin L / Jansen, Nathan K / Honko, Anna / Cardile, Anthony P

Viruses

2021 Volume 13, Issue 11

Abstract: Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are ... ...

Abstract	Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.
MeSH term(s)	Aerosols ; Animals ; Disease Models, Animal ; Ebolavirus/pathogenicity ; Female ; Hemorrhagic Fever, Ebola/etiology ; Hemorrhagic Fever, Ebola/immunology ; Hemorrhagic Fever, Ebola/pathology ; Hemorrhagic Fever, Ebola/virology ; Macaca mulatta ; Male ; RNA, Viral/blood ; Viral Load
Chemical Substances	Aerosols ; RNA, Viral
Language	English
Publishing date	2021-11-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112297
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Article: Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques

Downs, Isaac / Johnson, Joshua C. / Rossi, Franco / Dyer, David / Saunders, David L. / Twenhafel, Nancy A. / Esham, Heather L. / Pratt, William D. / Trefry, John / Zumbrun, Elizabeth / Facemire, Paul R. / Johnston, Sara C. / Tompkins, Erin L. / Jansen, Nathan K. / Honko, Anna / Cardile, Anthony P.

Viruses. 2021 Nov. 17, v. 13, no. 11

2021

Abstract	Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.
Keywords	Ebolavirus ; aerosols ; alkalosis ; animal models ; carbon dioxide ; cytokines ; death ; fever ; hypotension ; lactic acid ; liver ; mortality ; natural history ; partial pressure ; therapeutics ; viremia ; Africa
Language	English
Dates of publication	2021-1117
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112297
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Nipah virus persists in the brains of nonhuman primate survivors.

Liu, Jun / Coffin, Kayla M / Johnston, Sara C / Babka, April M / Bell, Todd M / Long, Simon Y / Honko, Anna N / Kuhn, Jens H / Zeng, Xiankun

JCI insight

2019 Volume 4, Issue 14

Abstract: Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes highly lethal henipavirus encephalitis in humans. Survivors develop various neurologic sequelae, including late-onset and relapsing encephalitis, several months up to several years ... ...

Abstract	Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes highly lethal henipavirus encephalitis in humans. Survivors develop various neurologic sequelae, including late-onset and relapsing encephalitis, several months up to several years following initial infection. However, the underlying pathology and disease mechanisms of persistent neurologic complications remain unknown. Here, we demonstrate persistent NiV infection in the brains of grivets that survived experimental exposure to NiV. Encephalitis affected the entire brains, with the majority of NiV detected in the neurons and microglia of the brainstems, cerebral cortices, and cerebella. We identified the vascular endothelium in the brain as an initial target of NiV infection during the acute phase of disease, indicating a primary path of entry for NiV into the brain. Notably, we were unable to detect NiV anywhere else except the brains in the examined survivors. Our findings indicate that late-onset and relapsing encephalitis of NiV in human survivors may be due to viral persistence in the brain and shed light on the pathogenesis of chronic henipavirus encephalitis.
MeSH term(s)	Animals ; Brain/blood supply ; Brain/pathology ; Brain/virology ; Chlorocebus aethiops ; Chronic Disease ; Communicable Diseases, Emerging/mortality ; Communicable Diseases, Emerging/pathology ; Communicable Diseases, Emerging/virology ; Disease Models, Animal ; Endothelium, Vascular/pathology ; Endothelium, Vascular/virology ; Henipavirus Infections/mortality ; Henipavirus Infections/pathology ; Henipavirus Infections/virology ; Humans ; Male ; Nipah Virus/isolation & purification ; Nipah Virus/pathogenicity ; Recurrence ; Survivors ; Zoonoses/mortality ; Zoonoses/pathology ; Zoonoses/virology
Language	English
Publishing date	2019-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.129629
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Article ; Online: Natural history of disease in cynomolgus monkeys exposed to Ebola virus Kikwit strain demonstrates the reliability of this non-human primate model for Ebola virus disease.

Niemuth, Nancy A / Fallacara, Dawn / Triplett, Cheryl A / Tamrakar, Sanjay M / Rajbhandari, Alisha / Florence, Clint / Ward, Lucy / Griffiths, Anthony / Carrion, Ricardo / Goez-Gazi, Yenny / Alfson, Kendra J / Staples, Hilary M / Brasel, Trevor / Comer, Jason E / Massey, Shane / Smith, Jeanon / Kocsis, Andrew / Lowry, Jake / Johnston, Sara C /

Nalca, Aysegul / Goff, Arthur J / Shurtleff, Amy C / Pitt, Margaret L / Trefry, John / Fay, Michael P

PloS one

2021 Volume 16, Issue 7, Page(s) e0252874

Abstract: Filoviruses (Family Filoviridae genera Ebolavirus and Marburgvirus) are negative-stranded RNA viruses that cause severe health effects in humans and non-human primates, including death. Except in outbreak settings, vaccines and other medical ... ...

Abstract	Filoviruses (Family Filoviridae genera Ebolavirus and Marburgvirus) are negative-stranded RNA viruses that cause severe health effects in humans and non-human primates, including death. Except in outbreak settings, vaccines and other medical countermeasures against Ebola virus (EBOV) will require testing under the FDA Animal Rule. Multiple vaccine candidates have been evaluated using cynomolgus monkeys (CM) exposed to EBOV Kikwit strain. To the best of our knowledge, however, animal model development data supporting the use of CM in vaccine research have not been submitted to the FDA. This study describes a large CM database (122 CM, 62 female and 60 male, age 2 to 9 years) and demonstrates the consistency of the CM model through time to death models and descriptive statistics. CMs were exposed to EBOV doses of 0.1 to 100,000 PFU in 33 studies conducted at three Animal Biosafety Level 4 facilities, by three exposure routes. Time to death was modeled using Cox proportional hazards models with a frailty term that incorporated study-to-study variability. Despite significant differences attributed to exposure variables, all CMs exposed to the 100 to 1,000 pfu doses commonly used in vaccine studies died or met euthanasia criteria within 21 days of exposure, median 7 days, 93% between 5 and 12 days of exposure. Moderate clinical signs were observed 4 to 5 days after exposure and preceded death or euthanasia by approximately one day. Viremia was detected within a few days of infection. Hematology indices were indicative of viremia and the propensity for hemorrhage with progression of Ebola viremia. Changes associated with coagulation parameters and platelets were consistent with coagulation disruption. Changes in leukocyte profiles were indicative of an acute inflammatory response. Increased liver enzymes were observed shortly after exposure. Taken together, these factors suggest that the cynomolgus monkey is a reliable animal model for human disease.
MeSH term(s)	Animals ; Disease Models, Animal ; Disease Outbreaks ; Ebolavirus/physiology ; Female ; Hemorrhagic Fever, Ebola ; Macaca fascicularis ; Male ; Reproducibility of Results ; Viral Load
Language	English
Publishing date	2021-07-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0252874
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Article ; Online: Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis.

Blair, Paul W / Keshtkar-Jahromi, Maryam / Psoter, Kevin J / Reisler, Ronald B / Warren, Travis K / Johnston, Sara C / Goff, Arthur J / Downey, Lydia G / Bavari, Sina / Cardile, Anthony P

Viruses

2018 Volume 10, Issue 11

Abstract: Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a ... ...

Abstract	Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.
MeSH term(s)	Animals ; Disease Models, Animal ; Injections, Intramuscular ; Macaca ; Marburg Virus Disease/pathology ; Marburgvirus/pathogenicity ; Retrospective Studies ; Survival Analysis ; United States ; Virulence
Language	English
Publishing date	2018-11-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v10110658
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Article ; Online: Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates.

Smith, Darci R / Johnston, Sara C / Piper, Ashley / Botto, Miriam / Donnelly, Ginger / Shamblin, Joshua / Albariño, César G / Hensley, Lisa E / Schmaljohn, Connie / Nichol, Stuart T / Bird, Brian H

PLoS neglected tropical diseases

2018 Volume 12, Issue 5, Page(s) e0006474

Abstract: Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this ...

Abstract	Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; Callithrix/immunology ; Callithrix/virology ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Humans ; Rift Valley Fever/immunology ; Rift Valley Fever/prevention & control ; Rift Valley Fever/virology ; Rift Valley fever virus/genetics ; Rift Valley fever virus/immunology ; Sequence Deletion ; Vaccination ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/immunology ; Viral Nonstructural Proteins/administration & dosage ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/immunology ; Viral Vaccines/administration & dosage ; Viral Vaccines/genetics ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Viral ; Vaccines, Attenuated ; Viral Nonstructural Proteins ; Viral Vaccines
Language	English
Publishing date	2018
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0006474
Database	MEDical Literature Analysis and Retrieval System OnLINE

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