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  1. Article ; Online: A Recombinant Vesicular Stomatitis Virus-Based Vaccine Provides Postexposure Protection Against Bundibugyo Ebolavirus Infection.

    Woolsey, Courtney / Strampe, Jamie / Fenton, Karla A / Agans, Krystle N / Martinez, Jasmine / Borisevich, Viktoriya / Dobias, Natalie S / Deer, Daniel J / Geisbert, Joan B / Cross, Robert W / Connor, John H / Geisbert, Thomas W

    The Journal of infectious diseases

    2023  Volume 228, Issue Suppl 7, Page(s) S712–S720

    Abstract: Background: The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector ... ...

    Abstract Background: The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector that expresses Ebola virus (EBOV) glycoprotein (GP). Ervebo was shown to rapidly protect against fatal Ebola disease in clinical trials; however, the vaccine is only indicated against EBOV. Recent outbreaks of other filoviruses underscore the need for additional vaccine candidates, particularly for BDBV infections.
    Methods: To examine whether the rVSV vaccine candidate rVSVΔG/BDBV-GP could provide therapeutic protection against BDBV, we inoculated seven cynomolgus macaques with 1000 plaque-forming units of BDBV, administering rVSVΔG/BDBV-GP vaccine to 6 of them 20-23 minutes after infection.
    Results: Five of the treated animals survived infection (83%) compared to an expected natural survival rate of 21% in this macaque model. All treated animals showed an early circulating immune response, while the untreated animal did not. Surviving animals showed evidence of both GP-specific IgM and IgG production, while animals that succumbed did not produce significant IgG.
    Conclusions: This small, proof-of-concept study demonstrated early treatment with rVSVΔG/BDBV-GP provides a survival benefit in this nonhuman primate model of BDBV infection, perhaps through earlier initiation of adaptive immunity.
    MeSH term(s) Animals ; Hemorrhagic Fever, Ebola ; Ebolavirus ; Vesicular Stomatitis/prevention & control ; Antibodies, Viral ; Vesiculovirus/genetics ; Glycoproteins/genetics ; Viral Vaccines ; Macaca fascicularis ; Immunoglobulin G ; Ebola Vaccines
    Chemical Substances Antibodies, Viral ; Glycoproteins ; Viral Vaccines ; Immunoglobulin G ; Ebola Vaccines
    Language English
    Publishing date 2023-06-08
    Publishing country United States
    Document type 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/jiad207
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Viral immunity: Basic mechanisms and therapeutic applications-a Keystone Symposia report.

    Cable, Jennifer / Balachandran, Siddharth / Daley-Bauer, Lisa P / Rustagi, Arjun / Antony, Ferrin / Frere, Justin J / Strampe, Jamie / Kedzierska, Katherine / Cannon, Judy L / McGargill, Maureen A / Weiskopf, Daniela / Mettelman, Robert C / Niessl, Julia / Thomas, Paul G / Briney, Bryan / Valkenburg, Sophie A / Bloom, Jesse D / Bjorkman, Pamela J / Iketani, Sho /
    Rappazzo, C Garrett / Crooks, Chelsea M / Crofts, Kali F / Pöhlmann, Stefan / Krammer, Florian / Sant, Andrea J / Nabel, Gary J / Schultz-Cherry, Stacey

    Annals of the New York Academy of Sciences

    2023  Volume 1521, Issue 1, Page(s) 32–45

    Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses ... ...

    Abstract Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.
    MeSH term(s) Humans ; Pandemics ; Influenza, Human/epidemiology
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Viral immunity

    Cable, Jennifer / Balachandran, Siddharth / Daley-Bauer, Lisa P. / Rustagi, Arjun / Antony, Ferrin / Frere, Justin J. / Strampe, Jamie / Kedzierska, Katherine / Cannon, Judy L. / McGargill, Maureen A. / Weiskopf, Daniela / Mettelman, Robert C. / Niessl, Julia / Thomas, Paul G. / Briney, Bryan / Valkenburg, Sophie A. / Bloom, Jesse D. / Bjorkman, Pamela J. / Iketani, Sho /
    Rappazzo, C. Garrett / Crooks, Chelsea M. / Crofts, Kali F. / Pöhlmann, Stefan / Krammer, Florian / Sant, Andrea J. / Nabel, Gary J. / Schultz-Cherry, Stacey

    Annals of the New York Academy of Sciences

    Basic mechanisms and therapeutic applications - A Keystone Symposia report

    2023  Volume 1521, Issue 1, Page(s) 32–45

    Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses ... ...

    Title translation Virale Immunität: Grundlegende Mechanismen und therapeutische Anwendungen - Ein Bericht des Keystone-Symposiums
    Abstract Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.
    Keywords Antibodies ; Antikörper ; COVID-19 ; Drohung ; Epidemics ; Epidemien ; Immune System ; Immunity (Disease) ; Immunität (Krankheit) ; Immunsystem ; Infectious Disorders ; Infektionskrankheiten ; Pandemics ; Pandemie ; Public Health ; Threat ; Viral Infections ; Viruserkrankungen ; Öffentliche Gesundheit
    Language English
    Document type Article
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14960
    Database PSYNDEX

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  4. Article ; Online: Factors associated with progression to death in patients with Lassa fever in Nigeria: an observational study.

    Strampe, Jamie / Asogun, Danny A / Speranza, Emily / Pahlmann, Meike / Soucy, Ali / Bockholt, Sabrina / Pallasch, Elisa / Becker-Ziaja, Beate / Duraffour, Sophie / Bhadelia, Nahid / Ighodalo, Yemisi / Oyakhilome, Jennifer / Omomoh, Emmanuel O / Olokor, Thomas / Adomeh, Donatus I / Ikponwonsa, Odia / Aire, Chris / Tobin, Ekaete / Akpede, Nosa /
    Okokhere, Peter O / Okogbenin, Sylvanus A / Akpede, George O / Muñoz-Fontela, César / Ogbaini-Emovon, Ephraim / Günther, Stephan / Connor, John H / Oestereich, Lisa

    The Lancet. Infectious diseases

    2021  Volume 21, Issue 6, Page(s) 876–886

    Abstract: Background: Lassa fever is endemic in several west African countries. Case-fatality rates ranging from 21% to 69% have been reported. The pathophysiology of the disease in humans and determinants of mortality remain poorly understood. We aimed to ... ...

    Abstract Background: Lassa fever is endemic in several west African countries. Case-fatality rates ranging from 21% to 69% have been reported. The pathophysiology of the disease in humans and determinants of mortality remain poorly understood. We aimed to determine host protein biomarkers capable of determining disease outcome.
    Methods: In this observational study, we analysed left-over blood samples from patients who tested positive for Lassa fever at Irrua Specialist Teaching Hospital, Nigeria, between January, 2014, and April, 2017. We measured viral load, concentrations of clinical chemistry parameters, and levels of 62 circulating proteins involved in inflammation, immune response, and haemostasis. Patients with a known outcome (survival or death) and at least 200 μL of good-quality diagnostic sample were included in logistic regression modelling to assess the correlation of parameters with Lassa fever outcome. Individuals who gave consent could further be enrolled into a longitudinal analysis to assess the association of parameters with Lassa fever outcome over time. Participants were divided into two datasets for the statistical analysis: a primary dataset (samples taken between Jan 1, 2014, and April 1, 2016), and a secondary dataset (samples taken between April 1, 2016, and April 1, 2017). Biomarkers were ranked by area under the receiver operating characteristic curve (AUC) from highest (most predictive) to lowest (least predictive).
    Findings: Of 554 patients who tested positive for Lassa fever during the study period, 201 (131 in the primary dataset and 70 in the secondary dataset) were included in the biomarker analysis, of whom 74 (49 in the primary dataset and 25 in the secondary dataset) had died and 127 (82 in the primary dataset and 45 in the secondary dataset) had survived. Cycle threshold values (indicating viral load) and levels of 18 host proteins at the time of admission to hospital were significantly correlated with fatal outcome. The best predictors of outcome in both datasets were plasminogen activator inhibitor-1 (PAI-1; AUC 0·878 in the primary dataset and 0·876 in the secondary dataset), soluble thrombomodulin (TM; 0·839 in the primary dataset and 0·875 in the secondary dataset), and soluble tumour necrosis factor receptor superfamily member 1A (TNF-R1; 0·807 in the primary dataset and 0·851 in the secondary dataset), all of which had higher prediction accuracy than viral load (0·774 in the primary dataset and 0·837 in the secondary dataset). Longitudinal analysis (150 patients, of whom 36 died) showed that of the biomarkers that were predictive at admission, PAI-1 levels consistently decreased to normal levels in survivors but not in those who died.
    Interpretation: The identification of PAI-1 and soluble TM as markers of fatal Lassa fever at admission, and of PAI-1 as a marker of fatal Lassa fever over time, suggests that dysregulated coagulation and fibrinolysis and endothelial damage have roles in the pathophysiology of Lassa fever, providing a mechanistic explanation for the association of Lassa fever with oedema and bleeding. These novel markers might aid in clinical risk stratification and disease monitoring.
    Funding: German Research Foundation, Leibniz Association, and US National Institutes of Health.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Humans ; Lassa Fever/diagnosis ; Lassa Fever/epidemiology ; Lassa Fever/mortality ; Lassa Fever/physiopathology ; Lassa virus/isolation & purification ; Logistic Models ; Male ; Middle Aged ; Mortality ; Nigeria/epidemiology ; Survival Rate ; Viral Load
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-01-20
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(20)30737-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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