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Article ; Online: Progress on the Prevention and Treatment of Hantavirus Disease.

Brocato, Rebecca L / Hooper, Jay W

2019 Volume 11, Issue 7

Abstract: Hantaviruses, members of the ... ...

Abstract	Hantaviruses, members of the order
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Amides/therapeutic use ; Animals ; Antiviral Agents/therapeutic use ; Clinical Trials as Topic ; Hantavirus/classification ; Hantavirus/genetics ; Hantavirus/immunology ; Hantavirus Infections/drug therapy ; Hantavirus Infections/prevention & control ; Hantavirus Infections/virology ; Hantavirus Pulmonary Syndrome/virology ; Hemorrhagic Fever with Renal Syndrome/virology ; Humans ; Immunotherapy ; Lactoferrin/therapeutic use ; Models, Animal ; Nucleosides/therapeutic use ; Piperidines/therapeutic use ; Pyrazines/therapeutic use ; Quinazolines/therapeutic use ; Recombinant Proteins ; Ribavirin/therapeutic use ; Triazoles/therapeutic use ; Vaccines, Synthetic ; Viral Vaccines
Chemical Substances	1-ribofuranosyl-3-ethynyl-(1,2,4)triazole ; Adrenal Cortex Hormones ; Amides ; Antiviral Agents ; Nucleosides ; Piperidines ; Pyrazines ; Quinazolines ; Recombinant Proteins ; Triazoles ; Vaccines, Synthetic ; Viral Vaccines ; Ribavirin (49717AWG6K) ; Lactoferrin (EC 3.4.21.-) ; favipiravir (EW5GL2X7E0) ; vandetanib (YO460OQ37K)
Language	English
Publishing date	2019-07-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v11070610
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Progress on the Prevention and Treatment of Hantavirus Disease

Brocato, Rebecca L / Hooper, Jay W

Viruses. 2019 July 04, v. 11, no. 7

2019

Abstract: Hantaviruses, members of the order Bunyavirales, family Hantaviridae, have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic ... ...

Abstract	Hantaviruses, members of the order Bunyavirales, family Hantaviridae, have a world-wide distribution and are responsible for greater than 150,000 cases of disease per year. The spectrum of disease associated with hantavirus infection include hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) also known as hantavirus cardiopulmonary syndrome (HCPS). There are currently no FDA-approved vaccines or treatments for these hantavirus diseases. This review provides a summary of the status of vaccine and antiviral treatment efforts including those tested in animal models or human clinical trials.
Keywords	Orthohantavirus ; animal models ; clinical trials ; fever ; humans ; vaccines
Language	English
Dates of publication	2019-0704
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v11070610
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study.

Paulsen, Grant C / Frenck, Robert / Tomashek, Kay M / Alarcon, Rodolfo M / Hensel, Elizabeth / Lowe, Ashley / Brocato, Rebecca L / Kwilas, Steve A / Josleyn, Matthew D / Hooper, Jay W

The Journal of infectious diseases

2023 Volume 229, Issue 1, Page(s) 30–38

Abstract: Background: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated.: Methods: Phase 1, double-blind, dose-escalation trial randomly assigned ... ...

Abstract	Background: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated. Methods: Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50). Results: While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197. Conclusions: This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response. Clinical Trials Registration. NCT03682107.
MeSH term(s)	Adult ; Humans ; Orthohantavirus ; Vaccines, DNA/adverse effects ; Antibodies, Neutralizing ; Hantavirus Pulmonary Syndrome ; DNA ; Immunogenicity, Vaccine ; Double-Blind Method ; Antibodies, Viral
Chemical Substances	Vaccines, DNA ; Antibodies, Neutralizing ; DNA (9007-49-2) ; Antibodies, Viral
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad235
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Article ; Online: Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters.

Brocato, Rebecca L / Kwilas, Steven A / Kim, Robert K / Zeng, Xiankun / Principe, Lucia M / Smith, Jeffrey M / Hooper, Jay W

NPJ vaccines

2021 Volume 6, Issue 1, Page(s) 16

Abstract: A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of ... ...

Abstract	A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.
Language	English
Publishing date	2021-01-25
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-020-00279-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Comparison of transcriptional responses between pathogenic and nonpathogenic hantavirus infections in Syrian hamsters using NanoString.

Brocato, Rebecca L / Altamura, Louis A / Carey, Brian D / Perley, Casey C / Blancett, Candace D / Minogue, Timothy D / Hooper, Jay W

PLoS neglected tropical diseases

2021 Volume 15, Issue 8, Page(s) e0009592

Abstract: Background: Syrian hamsters infected with Andes virus (ANDV) develop a disease that recapitulates many of the salient features of human hantavirus pulmonary syndrome (HPS), including lethality. Infection of hamsters with Hantaan virus (HTNV) results in ... ...

Abstract	Background: Syrian hamsters infected with Andes virus (ANDV) develop a disease that recapitulates many of the salient features of human hantavirus pulmonary syndrome (HPS), including lethality. Infection of hamsters with Hantaan virus (HTNV) results in an asymptomatic, disseminated infection. In order to explore this dichotomy, we examined the transcriptome of ANDV- and HTNV-infected hamsters. Results: Using NanoString technology, we examined kinetic transcriptional responses in whole blood collected from ANDV- and HTNV-infected hamsters. Of the 770 genes analyzed, key differences were noted in the kinetics of type I interferon sensing and signaling responses, complement activation, and apoptosis pathways between ANDV- and HTNV-infected hamsters. Conclusions: Delayed activation of type I interferon responses in ANDV-infected hamsters represents a potential mechanism that ANDV uses to subvert host immune responses and enhance disease. This is the first genome-wide analysis of hantavirus-infected hamsters and provides insight into potential avenues for therapeutics to hantavirus disease.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Cricetinae ; Female ; Hantavirus/genetics ; Hantavirus/isolation & purification ; Hantavirus/pathogenicity ; Hantavirus Infections/pathology ; Hantavirus Pulmonary Syndrome/pathology ; High-Throughput Nucleotide Sequencing/methods ; Mesocricetus ; Vero Cells
Language	English
Publishing date	2021-08-02
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0009592
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: SARS-CoV-2 Doggybone DNA Vaccine Produces Cross-Variant Neutralizing Antibodies and Is Protective in a COVID-19 Animal Model.

Mucker, Eric M / Brocato, Rebecca L / Principe, Lucia M / Kim, Robert K / Zeng, Xiankun / Smith, Jeffrey M / Kwilas, Steven A / Kim, Sungwon / Horton, Helen / Caproni, Lisa / Hooper, Jay W

Vaccines

2022 Volume 10, Issue 7

Abstract: To combat the COVID-19 pandemic, an assortment of vaccines has been developed. Nucleic acid vaccines have the advantage of rapid production, as they only require a viral antigen sequence and can readily be modified to detected viral mutations. Doggybone™ ...

Abstract	To combat the COVID-19 pandemic, an assortment of vaccines has been developed. Nucleic acid vaccines have the advantage of rapid production, as they only require a viral antigen sequence and can readily be modified to detected viral mutations. Doggybone™ DNA vaccines targeting the spike protein of SARS-CoV-2 have been generated and compared with a traditionally manufactured, bacterially derived plasmid DNA vaccine that utilizes the same spike sequence. Administered to Syrian hamsters by jet injection at two dose levels, the immunogenicity of both DNA vaccines was compared following two vaccinations. Immunized hamsters were then immunosuppressed and exposed to SARS-CoV-2. Significant differences in body weight were observed during acute infection, and lungs collected at the time of euthanasia had significantly reduced viral RNA, infectious virus, and pathology compared with irrelevant DNA-vaccinated controls. Moreover, immune serum from vaccinated animals was capable of neutralizing SARS-CoV-2 variants of interest and importance in vitro. These data demonstrate the efficacy of a synthetic DNA vaccine approach to protect hamsters from SARS-CoV-2.
Language	English
Publishing date	2022-07-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines10071104
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Article ; Online: Corrigendum to "Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses".

Golden, Joseph W / Hammerbeck, Christopher D / Mucker, Eric M / Brocato, Rebecca L

BioMed research international

2015 Volume 2015, Page(s) 313190

Language	English
Publishing date	2015
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2015/313190
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies.

eLife

2023 Volume 12

Abstract: Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% ... ...

Abstract	Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.
MeSH term(s)	Animals ; Humans ; Orthohantavirus ; Antibodies, Neutralizing ; Antibodies, Viral ; Hantavirus Infections/prevention & control ; Hantaan virus ; Communicable Diseases ; Rodentia
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-03-27
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.81743
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Article ; Online: SARS-CoV-2 Doggybone DNA Vaccine Produces Cross-Variant Neutralizing Antibodies and Is Protective in a COVID-19 Animal Model

Eric M. Mucker / Rebecca L. Brocato / Lucia M. Principe / Robert K. Kim / Xiankun Zeng / Jeffrey M. Smith / Steven A. Kwilas / Sungwon Kim / Helen Horton / Lisa Caproni / Jay W. Hooper

Vaccines, Vol 10, Iss 7, p

2022 Volume 1104

Abstract	To combat the COVID-19 pandemic, an assortment of vaccines has been developed. Nucleic acid vaccines have the advantage of rapid production, as they only require a viral antigen sequence and can readily be modified to detected viral mutations. Doggybone™ DNA vaccines targeting the spike protein of SARS-CoV-2 have been generated and compared with a traditionally manufactured, bacterially derived plasmid DNA vaccine that utilizes the same spike sequence. Administered to Syrian hamsters by jet injection at two dose levels, the immunogenicity of both DNA vaccines was compared following two vaccinations. Immunized hamsters were then immunosuppressed and exposed to SARS-CoV-2. Significant differences in body weight were observed during acute infection, and lungs collected at the time of euthanasia had significantly reduced viral RNA, infectious virus, and pathology compared with irrelevant DNA-vaccinated controls. Moreover, immune serum from vaccinated animals was capable of neutralizing SARS-CoV-2 variants of interest and importance in vitro. These data demonstrate the efficacy of a synthetic DNA vaccine approach to protect hamsters from SARS-CoV-2.
Keywords	doggybone DNA vaccine ; nucleic acid ; vaccine ; SARS-CoV-2 ; COVID-19 ; immunogenicity ; Medicine ; R
Subject code	612
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines.

Brocato, Rebecca L / Kwilas, Steven A / Josleyn, Matthew D / Long, Simon / Zeng, Xiankun / Perley, Casey C / Principe, Lucia M / Somerville, Brandon / Cohen, Melanie V / Hooper, Jay W

Vaccine

2021 Volume 39, Issue 7, Page(s) 1101–1110

Abstract: DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine ... ...

Abstract	DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.
MeSH term(s)	Animals ; Cricetinae ; Hantavirus/genetics ; Hantavirus Infections/prevention & control ; Immunogenicity, Vaccine ; Injections, Jet ; Vaccination/methods ; Vaccines, DNA/administration & dosage ; Viral Vaccines/administration & dosage
Chemical Substances	Vaccines, DNA ; Viral Vaccines
Language	English
Publishing date	2021-01-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2021.01.002
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