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  • 1
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    Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-04-23
    Description: The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467030/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467030/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thi, Emily P -- Mire, Chad E -- Lee, Amy C H -- Geisbert, Joan B -- Zhou, Joy Z -- Agans, Krystle N -- Snead, Nicholas M -- Deer, Daniel J -- Barnard, Trisha R -- Fenton, Karla A -- MacLachlan, Ian -- Geisbert, Thomas W -- U19 AI109711/AI/NIAID NIH HHS/ -- U19AI109711/AI/NIAID NIH HHS/ -- England -- Nature. 2015 May 21;521(7552):362-5. doi: 10.1038/nature14442. Epub 2015 Apr 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tekmira Pharmaceuticals, Burnaby, British Columbia V5J 5J8, Canada. ; 1] Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas 77550, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77550, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25901685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Disease Models, Animal ; Ebolavirus/classification/*drug effects/*genetics ; Female ; Hemorrhagic Fever, Ebola/pathology/prevention & control/*therapy/*virology ; Humans ; Macaca mulatta/virology ; Male ; Nanoparticles/*administration & dosage ; RNA, Small Interfering/*administration & dosage/pharmacology/*therapeutic use ; Survival Analysis ; Time Factors ; Treatment Outcome ; Viral Load/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-04-09
    Description: The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629916/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629916/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mire, Chad E -- Matassov, Demetrius -- Geisbert, Joan B -- Latham, Theresa E -- Agans, Krystle N -- Xu, Rong -- Ota-Setlik, Ayuko -- Egan, Michael A -- Fenton, Karla A -- Clarke, David K -- Eldridge, John H -- Geisbert, Thomas W -- R01 AI098817/AI/NIAID NIH HHS/ -- R01AI09881701/AI/NIAID NIH HHS/ -- U19 AI109711/AI/NIAID NIH HHS/ -- England -- Nature. 2015 Apr 30;520(7549):688-91. doi: 10.1038/nature14428. Epub 2015 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas 77550, USA [2] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77550, USA. ; Department of Virology and Vaccine Vectors, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA. ; Department of Immunology, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA. ; 1] Department of Virology and Vaccine Vectors, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA [2] Department of Immunology, Profectus BioSciences, Inc., Tarrytown, New York 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25853476" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Animals ; Antibodies, Viral/immunology ; Democratic Republic of the Congo/epidemiology ; Ebola Vaccines/*administration & dosage/genetics/*immunology ; Ebolavirus/classification/*immunology ; Female ; Genetic Vectors/genetics ; Hemorrhagic Fever, Ebola/immunology/*prevention & control/*virology ; Humans ; Immunoglobulin G/immunology ; Kinetics ; Macaca fascicularis ; Male ; Survival Analysis ; Vaccination ; Vaccines, Attenuated/administration & dosage/genetics/*immunology ; Vesiculovirus/*genetics/growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Monoclonal therapy of Argentine hemorrhagic fever [Immunology and Inflammation] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-04-20
    Description: Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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