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  1. Article ; Online: Low level of tonic interferon signalling is associated with enhanced susceptibility to SARS-CoV-2 variants of concern in human lung organoids.

    Flagg, Meaghan / Goldin, Kerry / Pérez-Pérez, Lizzette / Singh, Manmeet / Williamson, Brandi N / Pruett, Nathanael / Hoang, Chuong D / de Wit, Emmie

    Emerging microbes & infections

    2023  Volume 12, Issue 2, Page(s) 2276338

    Abstract: There is tremendous heterogeneity in the severity of COVID-19 disease in the human population, and the mechanisms governing the development of severe disease remain incompletely understood. The emergence of SARS-CoV-2 variants of concern (VOC) Delta (B.1. ...

    Abstract There is tremendous heterogeneity in the severity of COVID-19 disease in the human population, and the mechanisms governing the development of severe disease remain incompletely understood. The emergence of SARS-CoV-2 variants of concern (VOC) Delta (B.1.617.2) and Omicron (B.1.1.529) further compounded this heterogeneity. Virus replication and host cell damage in the distal lung is often associated with severe clinical disease, making this an important site to consider when evaluating pathogenicity of SARS-CoV-2 VOCs. Using distal human lung organoids (hLOs) derived from multiple human donors, we compared the fitness and pathogenicity of SARS-CoV-2 VOC Delta and Omicron, along with an ancestral clade B variant D614G, and evaluated donor-dependent differences in susceptibility to infection. We observed substantial attenuation of Omicron in hLOs and demonstrated enhanced susceptibility to Omicron and D614G replication in hLOs from one donor. Transcriptomic analysis revealed that increased susceptibility to SARS-CoV-2 infection in these hLOs was associated with reduced tonic interferon signaling activity at baseline. We show that hLOs can be used to model heterogeneity of SARS-CoV-2 pathogenesis in humans, and propose that variability in tonic interferon signaling set point may impact susceptibility to SARS-CoV-2 VOCs and subsequent COVID-19 disease progression.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Organoids ; Interferons/genetics
    Chemical Substances Interferons (9008-11-1)
    Language English
    Publishing date 2023-11-16
    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 10.1080/22221751.2023.2276338
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Late remdesivir treatment initiation partially protects African green monkeys from lethal Nipah virus infection.

    de Wit, Emmie / Williamson, Brandi N / Feldmann, Friederike / Goldin, Kerry / Lo, Michael K / Okumura, Atsushi / Lovaglio, Jamie / Bunyan, Elaine / Porter, Danielle P / Cihlar, Tomas / Saturday, Greg / Spiropoulou, Christina F / Feldmann, Heinz

    Antiviral research

    2023  Volume 216, Page(s) 105658

    Abstract: Remdesivir is a nucleotide prodrug with preclinical efficacy against lethal Nipah virus infection in African green monkeys when administered 1 day post inoculation (dpi) (Lo et al., 2019). Here, we determined whether remdesivir treatment was still ... ...

    Abstract Remdesivir is a nucleotide prodrug with preclinical efficacy against lethal Nipah virus infection in African green monkeys when administered 1 day post inoculation (dpi) (Lo et al., 2019). Here, we determined whether remdesivir treatment was still effective when treatment administration initiation was delayed until 3 dpi. Three groups of six African green monkeys were inoculated with a lethal dose of Nipah virus, genotype Bangladesh. On 3 dpi, one group received a loading dose of 10 mg/kg remdesivir followed by daily dosing with 5 mg/kg for 11 days, one group received 10 mg/kg on 12 consecutive days, and the remaining group received an equivalent volume of vehicle solution. Remdesivir treatment initiation on 3 dpi provided partial protection from severe Nipah virus disease that was dose dependent, with 67% of animals in the high dose group surviving the challenge. However, remdesivir treatment did not prevent clinical disease, and surviving animals showed histologic lesions in the brain. Thus, early administration seems critical for effective remdesivir treatment during Nipah virus infection.
    MeSH term(s) Animals ; Chlorocebus aethiops ; Henipavirus Infections/drug therapy ; Henipavirus Infections/prevention & control ; Brain ; Adenosine Monophosphate/pharmacology ; Adenosine Monophosphate/therapeutic use ; Alanine/pharmacology ; Alanine/therapeutic use ; Nipah Virus
    Chemical Substances remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2023-06-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2023.105658
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1627: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: ChAdOx1 NiV vaccination protects against lethal Nipah Bangladesh virus infection in African green monkeys.

    van Doremalen, Neeltje / Avanzato, Victoria A / Goldin, Kerry / Feldmann, Friederike / Schulz, Jonathan E / Haddock, Elaine / Okumura, Atsushi / Lovaglio, Jamie / Hanley, Patrick W / Cordova, Kathleen / Saturday, Greg / de Wit, Emmie / Lambe, Teresa / Gilbert, Sarah C / Munster, Vincent J

    NPJ vaccines

    2022  Volume 7, Issue 1, Page(s) 171

    Abstract: Nipah virus (NiV) is a highly pathogenic and re-emerging virus, which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal ... ...

    Abstract Nipah virus (NiV) is a highly pathogenic and re-emerging virus, which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal challenge with NiV Bangladesh (NiV-B) in hamsters. Here, we investigated the efficacy of ChAdOx1 NiV in the lethal African green monkey (AGM) NiV challenge model. AGMs were vaccinated either 4 weeks before challenge (prime vaccination), or 8 and 4 weeks before challenge with ChAdOx1 NiV (prime-boost vaccination). A robust humoral and cellular response was detected starting 14 days post-initial vaccination. Upon challenge, control animals displayed a variety of signs and had to be euthanized between 5 and 7 days post inoculation. In contrast, vaccinated animals showed no signs of disease, and we were unable to detect infectious virus in tissues and all but one swab. No to limited antibodies against fusion protein or nucleoprotein antigen could be detected 42 days post challenge, suggesting that vaccination induced a very robust protective immune response preventing extensive virus replication.
    Language English
    Publishing date 2022-12-21
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-022-00592-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Distinct VSV-based Nipah virus vaccines expressing either glycoprotein G or fusion protein F provide homologous and heterologous protection in a nonhuman primate model.

    de Wit, Emmie / Feldmann, Friederike / Cronin, Jacqueline / Goldin, Kerry / Mercado-Hernandez, Reinaldo / Williamson, Brandi N / Meade-White, Kimberly / Okumura, Atsushi / Callison, Julie / Weatherman, Sarah / Rosenke, Rebecca / Avanzato, Victoria A / Lovaglio, Jamie / Scott, Dana P / Marzi, Andrea / Feldmann, Heinz

    EBioMedicine

    2022  Volume 87, Page(s) 104405

    Abstract: Background: Nipah virus (NiV) causes recurrent outbreaks of lethal respiratory and neurological disease in Southeast Asia. The World Health Organization considers the development of an effective vaccine against NiV a priority.: Methods: We produced ... ...

    Abstract Background: Nipah virus (NiV) causes recurrent outbreaks of lethal respiratory and neurological disease in Southeast Asia. The World Health Organization considers the development of an effective vaccine against NiV a priority.
    Methods: We produced two NiV vaccine candidates using the licensed VSV-EBOV vaccine as a backbone and tested its efficacy against lethal homologous and heterologous NiV challenge with Nipah virus Bangladesh and Nipah virus Malaysia, respectively, in the African green monkey model.
    Findings: The VSV-EBOV vaccine expressing NiV glycoprotein G (VSV-NiVG) induced high neutralising antibody titers and afforded complete protection from homologous and heterologous challenge. The VSV-EBOV vaccine expressing NiV fusion protein F (VSV-NiVF) induced a lower humoral response and afforded complete homologous protection, but only partial heterologous protection. Both vaccines reduced virus shedding from the upper respiratory tract, and virus replication in the lungs and central nervous system. None of the protected animals vaccinated with VSV-NiVG or VSV-NiVF showed histological lesions in the CNS, but one VSV-NiVF-vaccinated animal that was not protected developed severe meningoencephalitis.
    Interpretation: The VSV-NiVG vaccine offers broad protection against NiV disease.
    Funding: This study was supported by the Intramural Research Program, NIAID, NIH.
    MeSH term(s) Animals ; Chlorocebus aethiops ; Nipah Virus/genetics ; Viral Vaccines/genetics ; Virus Replication ; Primates ; Bangladesh
    Chemical Substances Viral Vaccines
    Language English
    Publishing date 2022-12-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104405
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7090: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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