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Article ; Online: Zika virus vertical transmission in interferon receptor1-antagonized Rag1

Winkler, Clayton W / Clancy, Chad S / Rosenke, Rebecca / Peterson, Karin E

2022 Volume 10, Issue 1, Page(s) 46

Abstract: The mechanisms by which vertically transmitted Zika virus (ZIKV) causes postnatal brain development abnormalities and congenital disease remain poorly understood. Here, we optimized the established anti-IFNAR1 treated, ... ...

Abstract	The mechanisms by which vertically transmitted Zika virus (ZIKV) causes postnatal brain development abnormalities and congenital disease remain poorly understood. Here, we optimized the established anti-IFNAR1 treated, Rag1
MeSH term(s)	Animals ; Brain/pathology ; Brain Diseases/complications ; Female ; Homeodomain Proteins ; Interferons ; Mice ; Pregnancy ; Receptor, Interferon alpha-beta ; Zika Virus/physiology ; Zika Virus Infection/complications ; Zika Virus Infection/genetics
Chemical Substances	Homeodomain Proteins ; Ifnar1 protein, mouse ; RAG-1 protein (128559-51-3) ; Receptor, Interferon alpha-beta (156986-95-7) ; Interferons (9008-11-1)
Language	English
Publishing date	2022-04-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-022-01351-6
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Article ; Online: Histopathologic Characterization of Experimental Peracute SARS-CoV-2 Infection in the Syrian Hamster.

Clancy, Chad S / Meade-White, Kimberly / Shaia, Carl / Saturday, Greg / Feldmann, Heinz / Rosenke, Kyle

Veterinary sciences

2023 Volume 10, Issue 9

Abstract: Coronavirus Infectious Disease 2019 (COVID-19) initiated a global pandemic that thus far has resulted in the death of over 6.5 million people internationally. Understanding the viral tropism during the initial, subclinical phase of infection is critical ... ...

Abstract	Coronavirus Infectious Disease 2019 (COVID-19) initiated a global pandemic that thus far has resulted in the death of over 6.5 million people internationally. Understanding the viral tropism during the initial, subclinical phase of infection is critical to develop targeted vaccines and therapeutics. With the continued emergence of variants of concern, particularly those that appear to have a tropism for the upper respiratory tract, understanding the complete pathogenesis is critical to develop more effective interventions. Thus far, the Syrian hamster has served as the most consistent small animal model of SARS-CoV-2 infection for mild to moderate respiratory disease. Herein, we utilize histopathology and immunohistochemistry to characterize the peracute phase of disease initiating at 6-h-post-inoculation in the intranasal inoculation route Syrian hamster model. Inflammation and viral replication initiates in the respiratory epithelium of nasal turbinates as early as 12-h-post-inoculation and moves caudally through the nasal cavity by 36-h-post inoculation. Lower respiratory involvement can be detected as early as 12-h-post inoculation in the intranasal inoculated hamster model. These data highlight the importance of rostral nasal cavity sampling at early timepoints for detection of SARS-CoV-2 in the Syrian hamster model.
Language	English
Publishing date	2023-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci10090536
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Article ; Online: Protection from COVID-19 with a VSV-based vaccine expressing the spike and nucleocapsid proteins.

O'Donnell, Kyle L / Gourdine, Tylisha / Fletcher, Paige / Clancy, Chad S / Marzi, Andrea

Frontiers in immunology

2022 Volume 13, Page(s) 1025500

Abstract: Successful vaccine efforts countering the COVID-19 pandemic are centralized around the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein as viral antigen and have greatly reduced the morbidity and mortality associated with ... ...

Abstract	Successful vaccine efforts countering the COVID-19 pandemic are centralized around the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein as viral antigen and have greatly reduced the morbidity and mortality associated with COVID-19. Since the start of this pandemic, SARS-CoV-2 has evolved resulting in new variants of concern (VOC) challenging the vaccine-established immunologic memory. We show that vaccination with a vesicular stomatitis virus (VSV)-based vaccine expressing the SARS-CoV-2 S plus the conserved nucleocapsid (N) protein was protective in a hamster challenge model when a single dose was administered 28 or 10 days prior to challenge, respectively. In this study, only intranasal vaccination resulted in protection against challenge with multiple VOC highlighting that the addition of the N protein indeed improved protective efficacy. This data demonstrates the ability of a VSV-based dual-antigen vaccine to reduce viral shedding and protect from disease caused by SARS-CoV-2 VOC.
MeSH term(s)	Cricetinae ; Animals ; Humans ; COVID-19/prevention & control ; Nucleocapsid Proteins ; SARS-CoV-2 ; Pandemics ; Viral Vaccines
Chemical Substances	Nucleocapsid Proteins ; Viral Vaccines
Language	English
Publishing date	2022-10-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1025500
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Article ; Online: Establishing a Mouse Model for Sexual Transmission and Male Reproductive Tract Persistence of Ebola Virus.

Clancy, Chad S / Smart, Gabrielle / Rhoderick, J Fred / O'Donnell, Kyle L / Rosenke, Rebecca / Schäfer, Alexandra / Marzi, Andrea

The Journal of infectious diseases

2023 Volume 228, Issue Suppl 7, Page(s) S554–S558

Abstract: Ebola virus disease (EVD) has resulted in the death of over 15 000 people since its discovery in 1976. At least 1 incident of re-emergence of EVD has been associated with persistent male reproductive tract infection in a patient surviving EVD greater ... ...

Abstract	Ebola virus disease (EVD) has resulted in the death of over 15 000 people since its discovery in 1976. At least 1 incident of re-emergence of EVD has been associated with persistent male reproductive tract infection in a patient surviving EVD greater than 500 days prior. To date, animal models of Ebola virus (EBOV) infection have failed to fully characterize the pathogenesis of reproductive tract infection. Furthermore, no animal model of sexual transmission of EBOV exists. In this study, we describe a roadmap to modeling sexual transmission of EBOV using a mouse-adapted EBOV isolate in immunocompetent male mice and female Ifnar-/- mice.
MeSH term(s)	Animals ; Humans ; Male ; Female ; Ebolavirus ; Hemorrhagic Fever, Ebola ; Reproductive Tract Infections ; Disease Models, Animal
Language	English
Publishing date	2023-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad118
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Article ; Online: Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine.

O'Donnell, Kyle L / Feldmann, Friederike / Kaza, Benjamin / Clancy, Chad S / Hanley, Patrick W / Fletcher, Paige / Marzi, Andrea

EBioMedicine

2023 Volume 89, Page(s) 104463

Abstract: Background: Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD) which has a case fatality rate up to ∼90% in humans. Recently, there were cases reported in Guinea and Ghana highlighting this virus as a high-consequence pathogen ... ...

Abstract	Background: Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD) which has a case fatality rate up to ∼90% in humans. Recently, there were cases reported in Guinea and Ghana highlighting this virus as a high-consequence pathogen potentially threatening global public health. There are no licensed treatments or vaccines available today. We used a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV-Angola glycoprotein (VSV-MARV) as the viral antigen. Previously, a single dose of 1 × 10 Methods: As we sought to lower the vaccination dose to achieve a higher number of vaccine doses per vial, we administered 1 × 10 Results: Vaccination resulted in uniform protection with no detectable viremia. Antigen-specific IgG responses were induced by both vaccine concentrations and were sustained until the study endpoint. Neutralizing antibody responses and antibody-dependent cellular phagocytosis were observed. The cellular response after vaccination was characterized by an early induction of NK cell activation. Additionally, antigen-specific memory T cell subsets were detected in all vaccination cohorts indicating that while the primary protective mechanism of VSV-MARV is the humoral response, a functional cellular response is also induced. Interpretation: Overall, this data highlights VSV-MARV as a viable and fast-acting MARV vaccine candidate suitable for deployment in emergency outbreak situations and supports its clinical development. Funding: This work was funded by the Intramural Research Program NIAID, NIH.
MeSH term(s)	Animals ; Humans ; Marburg Virus Disease/prevention & control ; Viral Vaccines ; Macaca fascicularis ; Vaccination ; Antibodies, Neutralizing
Chemical Substances	Viral Vaccines ; Antibodies, Neutralizing
Language	English
Publishing date	2023-02-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104463
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Article ; Online: Camelid Inoculation With Middle East Respiratory Syndrome Coronavirus: Experimental Models of Reservoir Host Infection.

Adney, Danielle R / Clancy, Chad S / Bowen, Richard A / Munster, Vincent J

Viruses

2020 Volume 12, Issue 12

Abstract: Within the past two decades, three zoonotic betacoronaviruses have been associated with outbreaks causing severe respiratory disease in humans. Of these, Middle East respiratory s yndrome coronavirus (MERS-CoV) is the only zoonotic coronavirus that is ... ...

Abstract	Within the past two decades, three zoonotic betacoronaviruses have been associated with outbreaks causing severe respiratory disease in humans. Of these, Middle East respiratory s yndrome coronavirus (MERS-CoV) is the only zoonotic coronavirus that is known to consistently result in frequent zoonotic spillover events from the proximate reservoir host-the dromedary camel. A comprehensive understanding of infection in dromedaries is critical to informing public health recommendations and implementing intervention strategies to mitigate spillover events. Experimental models of reservoir disease are absolutely critical in understanding the pathogenesis and transmission, and are key to testing potential dromedary vaccines against MERS-CoV. In this review, we describe experimental infections of dromedary camels as well as additional camelid models used to further understand the camel's role in MERS-CoV spillover to humans.
MeSH term(s)	Animals ; Camelus/virology ; Coronavirus Infections/pathology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Disease Reservoirs/virology ; Humans ; Middle East Respiratory Syndrome Coronavirus/pathogenicity ; Middle East Respiratory Syndrome Coronavirus/physiology ; Models, Biological ; Vaccination/veterinary ; Virus Shedding ; Zoonoses/prevention & control ; Zoonoses/transmission ; Zoonoses/virology
Language	English
Publishing date	2020-11-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12121370
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Article: VSV-Based Vaccines Reduce Virus Shedding and Viral Load in Hamsters Infected with SARS-CoV-2 Variants of Concern.

O'Donnell, Kyle L / Gourdine, Tylisha / Fletcher, Paige / Shifflett, Kyle / Furuyama, Wakako / Clancy, Chad S / Marzi, Andrea

Vaccines

2022 Volume 10, Issue 3

Abstract: The continued progression of the COVID-19 pandemic can partly be attributed to the ability of SARS-CoV-2 to mutate and introduce new viral variants. Some of these variants with the potential to spread quickly and conquer the globe are termed variants of ... ...

Abstract	The continued progression of the COVID-19 pandemic can partly be attributed to the ability of SARS-CoV-2 to mutate and introduce new viral variants. Some of these variants with the potential to spread quickly and conquer the globe are termed variants of concern (VOC). The existing vaccines implemented on a global scale are based on the ancestral strain, which has resulted in increased numbers of breakthrough infections as these VOC have emerged. It is imperative to show protection against VOC infection with newly developed vaccines. Previously, we evaluated two vesicular stomatitis virus (VSV)-based vaccines expressing the SARS-CoV-2 spike protein alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV) and demonstrated their fast-acting potential. Here, we prolonged the time to challenge; we vaccinated hamsters intranasally (IN) or intramuscularly 28 days prior to infection with three SARS-CoV-2 VOC-the Alpha, Beta, and Delta variants. IN vaccination with either the VSV-SARS2 or VSV-SARS2-EBOV resulted in the highest protective efficacy as demonstrated by decreased virus shedding and lung viral load of vaccinated hamsters. Histopathologic analysis of the lungs revealed the least amount of lung damage in the IN-vaccinated animals regardless of the challenge virus. This data demonstrates the ability of a VSV-based vaccine to not only protect from disease caused by SARS-CoV-2 VOC but also reduce viral shedding.
Language	English
Publishing date	2022-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines10030435
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Article ; Online: Incomplete Urethral Duplication Associated with a Dermoid Cyst within a Vascular Hamartoma in a Female Dog.

Clancy, Chad S / Hullinger, Gordon A / Van Wettere, Arnaud J

Veterinary sciences

2019 Volume 6, Issue 2

Abstract: A seven-year-old spayed female Labrador retriever presented for necropsy following an acute history of thrombocytopenia, anemia, leukocytosis and abdominal effusion. A 2 × 3 × 10 cm, cylindrical to tubular, mottled red-to-tan mass extended from the ... ...

Abstract	A seven-year-old spayed female Labrador retriever presented for necropsy following an acute history of thrombocytopenia, anemia, leukocytosis and abdominal effusion. A 2 × 3 × 10 cm, cylindrical to tubular, mottled red-to-tan mass extended from the caudal pelvic cavity caudally and ventrally under the dermis along the caudal aspect of the left pelvic limb adjacent to the semimembranosus and semitendinosus musculature. Histologic examination of the mass revealed a singular central lumen lined by urothelium that multifocally transitioned into non-keratinizing, stratified squamous epithelium associated with few hair follicles and sweat glands. The lumen was surrounded by a dense collagenous stroma containing numerous, variably sized blood vessels. The combination of lesions was consistent with a diagnosis of incomplete urethral duplication associated with a dermoid cyst and vascular hamartoma. To the authors' knowledge, this is the first report of an incomplete urethral duplication associated with a dermoid cyst within a vascular hamartoma.
Language	English
Publishing date	2019-05-30
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci6020050
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Article: Histologic pulmonary lesions of SARS-CoV-2 in 4 nonhuman primate species: An institutional comparative review

Clancy, Chad S. / Shaia, Carl / Munster, Vincent / de Wit, Emmie / Hawman, David / Okumura, Atsushi / Feldmann, Heinz / Saturday, Greg / Scott, Dana

Veterinary pathology. 2022 July, v. 59, no. 4

2022

Abstract: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emergent, amphixenotic infection that resulted in a pandemic declaration in March 2020. A rapid search for appropriate animal models of ...

Abstract	Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emergent, amphixenotic infection that resulted in a pandemic declaration in March 2020. A rapid search for appropriate animal models of this newly emergent viral respiratory disease focused initially on traditional nonhuman primate research species. Nonhuman primate models have previously been shown to be valuable in evaluation of emerging respiratory coronaviruses with pandemic potential (ie, SARS-CoV and Middle East respiratory syndrome coronavirus). In this article, we review the pulmonary histopathologic characteristics and immunohistochemical evaluation of experimental SARS-CoV-2 infection in the rhesus macaque, pigtail macaque, African green monkey, and squirrel monkey. Our results indicate that all evaluated nonhuman primate species developed variably severe histopathologic changes typical of coronavirus respiratory disease characterized by interstitial pneumonia with or without syncytial cell formation, alveolar fibrin, and pulmonary edema that progressed to type II pneumocyte hyperplasia. Lesion distribution was multifocal, frequently subpleural, and often more severe in lower lung lobes. However, squirrel monkeys showed the least severe and least consistent lesions of the evaluated nonhuman primates. Additionally, our results highlight the disparate physical relationship between viral antigen and foci of pulmonary lesions. While classic respiratory coronaviral lesions were observed in the lungs of all nonhuman primates evaluated, none of the primates exhibited severe lesions or evidence of diffuse alveolar damage and therefore are unlikely to represent the severe form of SARS-CoV-2 infection observed in fatal human cases.
Keywords	COVID-19 infection ; Cercopithecus aethiops ; Macaca mulatta ; Middle East respiratory syndrome coronavirus ; Saimiri ; Severe acute respiratory syndrome coronavirus 2 ; animal pathology ; edema ; fibrin ; histopathology ; humans ; hyperplasia ; immunohistochemistry ; pandemic ; pneumocytes ; pneumonia ; squirrels ; viral antigens
Language	English
Dates of publication	2022-07
Size	p. 673-680.
Publishing place	SAGE Publications
Document type	Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/03009858211067468
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Single-dose VSV-based vaccine protects cynomolgus macaques from disease after Taï Forest virus infection.

Fletcher, Paige / O'Donnell, Kyle L / Doratt, Brianna M / Malherbe, Delphine C / Clancy, Chad S / Rhoderick, Joseph F / Feldmann, Friederike / Hanley, Patrick W / Ksiazek, Thomas G / Geisbert, Thomas W / Messaoudi, Ilhem / Marzi, Andrea

Emerging microbes & infections

2023 Volume 12, Issue 2, Page(s) 2239950

Abstract: Taï Forest virus (TAFV) is a lesser-known ebolavirus that causes lethal infections in chimpanzees and is responsible for a single human case. Limited research has been done on this human pathogen; however, with the recent emergence of filoviruses in West ...

Abstract	Taï Forest virus (TAFV) is a lesser-known ebolavirus that causes lethal infections in chimpanzees and is responsible for a single human case. Limited research has been done on this human pathogen; however, with the recent emergence of filoviruses in West Africa, further investigation and countermeasure development against this virus is warranted. We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the TAFV glycoprotein as the viral antigen and assessed it for protective efficacy in nonhuman primates (NHPs). Following a single high-dose vaccination, NHPs developed antigen-specific binding and neutralizing antibodies as well as modest T cell responses. Importantly, all vaccinated NHPs were uniformly protected from disease after lethal TAFV challenge while the naïve control group succumbed to the disease. Histopathologic lesions consistent with filovirus disease were present in control NHPs but were not observed in vaccinated NHPs. Transcriptional analysis of whole blood samples obtained after vaccination and challenge was performed to gain insight into molecular underpinnings conferring protection. Differentially expressed genes (DEG) detected 7 days post-vaccination were enriched to processes associated with innate immunity and antiviral responses. Only a small number of DEG was detected in vaccinated NHPs post-challenge while over 1,000 DEG were detected in control NHPs at end-stage disease which mapped to gene ontology terms indicative of defense responses and inflammation. Taken together, this data demonstrates the effective single-dose protection of the VSV-TAFV vaccine, and its potential for use in outbreaks.
MeSH term(s)	Animals ; Humans ; Ebolavirus ; Hemorrhagic Fever, Ebola ; Macaca fascicularis ; Viral Vaccines ; Antibodies, Viral ; Forests
Chemical Substances	Viral Vaccines ; Antibodies, Viral
Language	English
Publishing date	2023-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2023.2239950
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