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  1. Article ; Online: Multiplexing mRNAs builds a "broad-immunity wall" against the flu.

    Catanzaro, Nicholas J / Martinez, David R

    Science immunology

    2023  Volume 8, Issue 79, Page(s) eadg4686

    Abstract: Delivery of mRNAs encoding influenza HA antigens covering all known subtypes and lineages elicits cross-reactive and protective immunity. ...

    Abstract Delivery of mRNAs encoding influenza HA antigens covering all known subtypes and lineages elicits cross-reactive and protective immunity.
    MeSH term(s) Humans ; Influenza, Human ; Orthomyxoviridae Infections ; Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Cross Reactions
    Chemical Substances Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus
    Language English
    Publishing date 2023-01-06
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adg4686
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology.

    Philip, Drake T / Goins, Nigel M / Catanzaro, Nicholas J / Misumi, Ichiro / Whitmire, Jason K / Atkins, Hannah M / Lazear, Helen M

    mBio

    2024  Volume 15, Issue 4, Page(s) e0262323

    Abstract: Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought ...

    Abstract Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen, herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (
    MeSH term(s) Humans ; Mice ; Animals ; Interferon Lambda ; Neutrophils ; Herpes Simplex ; Herpesvirus 1, Human ; Cytokines ; Interferon-alpha ; Mice, Knockout ; Antiviral Agents/pharmacology
    Chemical Substances Interferon Lambda ; Cytokines ; Interferon-alpha ; Antiviral Agents
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.02623-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A nano-luciferase expressing human coronavirus OC43 for countermeasure development.

    Diefenbacher, Meghan V / Baric, Thomas J / Martinez, David R / Baric, Ralph S / Catanzaro, Nicholas J / Sheahan, Timothy P

    Virus research

    2023  Volume 339, Page(s) 199286

    Abstract: The genetic diversity of the coronavirus (CoV) family poses a significant challenge for drug discovery and development. Traditional antiviral drugs often target specific viral proteins from specific viruses which limits their use, especially against ... ...

    Abstract The genetic diversity of the coronavirus (CoV) family poses a significant challenge for drug discovery and development. Traditional antiviral drugs often target specific viral proteins from specific viruses which limits their use, especially against novel emerging viruses. Antivirals with broad-spectrum activity overcome this limitation by targeting highly conserved regions or catalytic domains within viral proteins that are essential for replication. For rapid identification of small molecules with broad antiviral activity, assays with viruses representing family-wide genetic diversity are needed. Viruses engineered to express a reporter gene (i.e. luminescence, fluorescence, etc.) can increase the efficiency, sensitivity or precision of drug screening over classical measures of replication like observation of cytopathic effect or measurement of infectious titers. We have previously developed reporter virus systems for multiple other endemic, pandemic, epidemic and enzootic CoV. Human CoV OC43 (HCoV-OC43) is a human endemic CoV that causes respiratory infection with age-related exacerbations of pathogenesis. Here, we describe the development of a novel recombinant HCoV-OC43 reporter virus that expresses nano-luciferase (HCoV-OC43 nLuc), and its potential application for screening of antivirals against CoV.
    MeSH term(s) Humans ; Coronavirus OC43, Human/genetics ; Coronavirus/genetics ; Coronavirus Infections ; Viral Proteins ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use
    Chemical Substances Viral Proteins ; Antiviral Agents
    Language English
    Publishing date 2023-12-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2023.199286
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1965: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology.

    Philip, Drake T / Goins, Nigel M / Catanzaro, Nicholas J / Misumi, Ichiro / Whitmire, Jason K / Atkins, Hannah M / Lazear, Helen M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought ...

    Abstract Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.11.557277
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.

    Chao, Cara W / Sprouse, Kaitlin R / Miranda, Marcos C / Catanzaro, Nicholas J / Hubbard, Miranda L / Addetia, Amin / Stewart, Cameron / Brown, Jack T / Dosey, Annie / Valdez, Adian / Ravichandran, Rashmi / Hendricks, Grace G / Ahlrichs, Maggie / Dobbins, Craig / Hand, Alexis / Treichel, Catherine / Willoughby, Isabelle / Walls, Alexandra C / McGuire, Andrew T /
    Leaf, Elizabeth M / Baric, Ralph S / Schäfer, Alexandra / Veesler, David / King, Neil P

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and ... ...

    Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.13.584735
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: mRNA-LNP vaccine-induced CD8

    Montoya, Brian / Melo-Silva, Carolina R / Tang, Lingjuan / Kafle, Samita / Lidskiy, Peter / Bajusz, Csaba / Vadovics, Máté / Muramatsu, Hiromi / Abraham, Edit / Lipinszki, Zoltan / Chatterjee, Debotri / Scher, Gabrielle / Benitez, Juliana / Sung, Molly M H / Tam, Ying K / Catanzaro, Nicholas J / Schäfer, Alexandra / Andino, Raul / Baric, Ralph S /
    Martinez, David R / Pardi, Norbert / Sigal, Luis J

    Molecular therapy : the journal of the American Society of Gene Therapy

    2024  

    Abstract: The role of ... ...

    Abstract The role of CD8
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2024.04.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5640: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Human ACE2 expression, a major tropism determinant for SARS-CoV-2, is regulated by upstream and intragenic elements.

    Snouwaert, John N / Jania, Leigh A / Nguyen, Trang / Martinez, David R / Schäfer, Alexandra / Catanzaro, Nicholas J / Gully, Kendra L / Baric, Ralph S / Heise, Mark / Ferris, Martin T / Anderson, Elizabeth / Pressey, Katia / Dillard, Jacob A / Taft-Benz, Sharon / Baxter, Victoria K / Ting, Jenny P-Y / Koller, Beverly H

    PLoS pathogens

    2023  Volume 19, Issue 2, Page(s) e1011168

    Abstract: Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines in which the Ace2 locus has been humanized by syntenic ...

    Abstract Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines in which the Ace2 locus has been humanized by syntenic replacement, we show that regulation of basal and interferon induced ACE2 expression, relative expression levels of different ACE2 transcripts, and sexual dimorphism in ACE2 expression are unique to each species, differ between tissues, and are determined by both intragenic and upstream promoter elements. Our results indicate that the higher levels of expression of ACE2 observed in the lungs of mice relative to humans may reflect the fact that the mouse promoter drives expression of ACE2 in populous airway club cells while the human promoter drives expression in alveolar type 2 (AT2) cells. In contrast to transgenic mice in which human ACE2 is expressed in ciliated cells under the control of the human FOXJ1 promoter, mice expressing ACE2 in club cells under the control of the endogenous Ace2 promoter show a robust immune response after infection with SARS-CoV-2, leading to rapid clearance of the virus. This supports a model in which differential expression of ACE2 determines which cell types in the lung are infected, and this in turn modulates the host response and outcome of COVID-19.
    MeSH term(s) Animals ; Humans ; Mice ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/genetics ; Mice, Transgenic ; Receptors, Virus/genetics ; SARS-CoV-2 ; Viral Tropism
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Receptors, Virus ; ACE2 protein, human (EC 3.4.17.23)
    Language English
    Publishing date 2023-02-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011168
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  8. Article ; Online: Mapping of susceptibility loci for Ebola virus pathogenesis in mice.

    Schäfer, Alexandra / Marzi, Andrea / Furuyama, Wakako / Catanzaro, Nicholas J / Nguyen, Cameron / Haddock, Elaine / Feldmann, Friederike / Meade-White, Kimberly / Thomas, Tina / Hubbard, Miranda L / Gully, Kendra L / Leist, Sarah R / Hock, Pablo / Bell, Timothy A / De la Cruz, Gabriela E / Midkiff, Bentley R / Martinez, David R / Shaw, Ginger D / Miller, Darla R /
    Vernon, Michael J / Graham, Rachel L / Cowley, Dale O / Montgomery, Stephanie A / Schughart, Klaus / de Villena, Fernando Pardo Manuel / Wilkerson, Gregory K / Ferris, Martin T / Feldmann, Heinz / Baric, Ralph S

    Cell reports

    2024  Volume 43, Issue 5, Page(s) 114127

    Abstract: Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference ... ...

    Abstract Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.
    Language English
    Publishing date 2024-04-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.114127
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  9. Article ; Online: Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice.

    Martinez, David R / Schäfer, Alexandra / Gavitt, Tyler D / Mallory, Michael L / Lee, Esther / Catanzaro, Nicholas J / Chen, Haiyan / Gully, Kendra / Scobey, Trevor / Korategere, Pooja / Brown, Alecia / Smith, Lena / Parks, Robert / Barr, Maggie / Newman, Amanda / Bowman, Cindy / Powers, John M / Soderblom, Erik J / Mansouri, Katayoun /
    Edwards, Robert J / Baric, Ralph S / Haynes, Barton F / Saunders, Kevin O

    Cell reports

    2023  Volume 42, Issue 10, Page(s) 113248

    Abstract: The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active ... ...

    Abstract The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.
    MeSH term(s) Animals ; Humans ; Mice ; Middle East Respiratory Syndrome Coronavirus ; COVID-19 Vaccines ; Severe acute respiratory syndrome-related coronavirus ; Antibodies, Viral ; Antibodies, Neutralizing ; SARS-CoV-2
    Chemical Substances COVID-19 Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Vaccine-mediated protection against merbecovirus and sarbecovirus challenge in mice.

    Martinez, David R / Schafer, Alexandra / Gavitt, Tyler D / Mallory, Michael L / Lee, Esther / Catanzaro, Nicholas J / Chen, Haiyan / Gully, Kendra / Scobey, Trevor / Korategere, Pooja / Brown, Alecia / Smith, Lena / Parks, Rob / Barr, Maggie / Newman, Amanda / Bowman, Cindy / Powers, John M / Mansouri, Katayoun / Edwards, Robert J /
    Baric, Ralph S / Haynes, Barton F / Saunders, Kevin O

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The emergence of three distinct highly pathogenic human coronaviruses - SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019 - underlines the need to develop broadly active vaccines against ... ...

    Abstract The emergence of three distinct highly pathogenic human coronaviruses - SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019 - underlines the need to develop broadly active vaccines against the
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.22.540829
    Database MEDical Literature Analysis and Retrieval System OnLINE

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