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  1. Artikel ; Online: Monoclonal antibody therapy demonstrates increased virulence of a lineage VII strain of Lassa virus in nonhuman primates.

    Woolsey, Courtney / Cross, Robert W / Prasad, Abhishek N / Agans, Krystle N / Borisevich, Viktoriya / Deer, Daniel J / Dobias, Natalie S / Fears, Alyssa C / Harrison, Mack B / Heinrich, Megan L / Fenton, Karla A / Garry, Robert F / Branco, Luis M / Geisbert, Thomas W

    Emerging microbes & infections

    2024  Band 13, Heft 1, Seite(n) 2301061

    Abstract: Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) ...

    Abstract Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the
    Mesh-Begriff(e) Humans ; Animals ; Lassa virus ; Lassa Fever ; Virulence ; Macaca fascicularis ; Antibodies, Monoclonal/pharmacology
    Chemische Substanzen Antibodies, Monoclonal
    Sprache Englisch
    Erscheinungsdatum 2024-01-22
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2023.2301061
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Oral administration of obeldesivir protects nonhuman primates against

    Cross, Robert W / Woolsey, Courtney / Chu, Victor C / Babusis, Darius / Bannister, Roy / Vermillion, Meghan S / Geleziunas, Romas / Barrett, Kimberly T / Bunyan, Elaine / Nguyen, Anh-Quan / Cihlar, Tomas / Porter, Danielle P / Prasad, Abhishek N / Deer, Daniel J / Borisevich, Viktoriya / Agans, Krystle N / Martinez, Jasmine / Harrison, Mack B / Dobias, Natalie S /
    Fenton, Karla A / Bilello, John P / Geisbert, Thomas W

    Science (New York, N.Y.)

    2024  Band 383, Heft 6688, Seite(n) eadk6176

    Abstract: Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS- ... ...

    Abstract Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV). We also report that once-daily oral ODV treatment of cynomolgus monkeys for 10 days beginning 24 hours after SUDV exposure confers 100% protection against lethal infection. Transcriptomics data show that ODV treatment delayed the onset of inflammation and correlated with antigen presentation and lymphocyte activation. Our results offer promise for the further development of ODV to control outbreaks of filovirus disease more rapidly.
    Mesh-Begriff(e) Animals ; Administration, Oral ; Ebolavirus/drug effects ; Hemorrhagic Fever, Ebola/drug therapy ; Hemorrhagic Fever, Ebola/prevention & control ; Macaca fascicularis ; Nucleosides/administration & dosage ; Nucleosides/pharmacology ; Adenosine Monophosphate/administration & dosage ; Adenosine Monophosphate/pharmacology ; Alanine/administration & dosage ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Prodrugs/administration & dosage ; Prodrugs/pharmacology ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacology
    Chemische Substanzen Nucleosides ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX) ; Prodrugs ; GS-441524 (1BQK176DT6) ; Antiviral Agents
    Sprache Englisch
    Erscheinungsdatum 2024-03-15
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adk6176
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: A Highly Attenuated Panfilovirus VesiculoVax Vaccine Rapidly Protects Nonhuman Primates Against Marburg Virus and 3 Species of Ebola Virus.

    Woolsey, Courtney / Borisevich, Viktoriya / Agans, Krystle N / O'Toole, Rachel / Fenton, Karla A / Harrison, Mack B / Prasad, Abhishek N / Deer, Daniel J / Gerardi, Cheryl / Morrison, Nneka / Cross, Robert W / Eldridge, John H / Matassov, Demetrius / Geisbert, Thomas W

    The Journal of infectious diseases

    2023  Band 228, Heft Suppl 7, Seite(n) S660–S670

    Abstract: Background: The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are considered the ... ...

    Abstract Background: The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are considered the deadliest. The vaccine, Ervebo, was shown to rapidly protect humans against Ebola disease, but is indicated only for EBOV infections with limited cross-protection against other filoviruses. Whether multivalent formulations of similar recombinant vesicular stomatitis virus (rVSV)-based vaccines could likewise confer rapid protection is unclear.
    Methods: Here, we tested the ability of an attenuated, quadrivalent panfilovirus VesiculoVax vaccine (rVSV-Filo) to elicit fast-acting protection against MARV, EBOV, SUDV, and BDBV. Groups of cynomolgus monkeys were vaccinated 7 days before exposure to each of the 4 viral pathogens. All subjects (100%) immunized 1 week earlier survived MARV, SUDV, and BDBV challenge; 80% survived EBOV challenge. Survival correlated with lower viral load, higher glycoprotein-specific immunoglobulin G titers, and the expression of B-cell-, cytotoxic cell-, and antigen presentation-associated transcripts.
    Conclusions: These results demonstrate multivalent VesiculoVax vaccines are suitable for filovirus outbreak management. The highly attenuated nature of the rVSV-Filo vaccine may be preferable to the Ervebo "delta G" platform, which induced adverse events in a subset of recipients.
    Mesh-Begriff(e) Humans ; Animals ; Ebolavirus ; Hemorrhagic Fever, Ebola ; Marburgvirus ; Vaccines, Attenuated ; Macaca fascicularis ; Viral Vaccines ; Vesiculovirus/genetics ; Vesicular stomatitis Indiana virus ; Antibodies, Viral ; Ebola Vaccines
    Chemische Substanzen Vaccines, Attenuated ; Viral Vaccines ; Antibodies, Viral ; Ebola Vaccines
    Sprache Englisch
    Erscheinungsdatum 2023-05-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad157
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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