{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:14:36Z","timestamp":1792181676944,"version":"4.4.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI119185, R01-AI132323"],"award-info":[{"award-number":["R01-AI119185, R01-AI132323"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30-GM103516"],"award-info":[{"award-number":["P30-GM103516"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UC7-AI094660"],"award-info":[{"award-number":["UC7-AI094660"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Ebola (EBOV), Marburg (MARV) and Sudan (SUDV) viruses are the three filoviruses which have caused the most fatalities in humans. Transmission from animals into the human population typically causes outbreaks of limited scale in endemic regions. In contrast, the 2013-16 outbreak in several West African countries claimed more than 11,000 lives revealing the true epidemic potential of filoviruses. This is further emphasized by the difficulty seen with controlling the 2018-2020 outbreak of EBOV in the Democratic Republic of Congo (DRC), despite the availability of two emergency use-approved vaccines and several experimental therapeutics targeting EBOV. Moreover, there are currently no vaccine options to protect against the other epidemic filoviruses. Protection of a monovalent EBOV vaccine against other filoviruses has never been demonstrated in primate challenge studies substantiating a significant void in capability should a MARV or SUDV outbreak of similar magnitude occur. Herein we show progress on developing vaccines based on recombinant filovirus glycoproteins (GP) from EBOV, MARV and SUDV produced using the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    S2 platform. The highly purified recombinant subunit vaccines formulated with CoVaccine HT\u2122 adjuvant have not caused any safety concerns (no adverse reactions or clinical chemistry abnormalities) in preclinical testing. Candidate formulations elicit potent immune responses in mice, guinea pigs and non-human primates (NHPs) and consistently produce high antigen-specific IgG titers. Three doses of an EBOV candidate vaccine elicit full protection against lethal EBOV infection in the cynomolgus challenge model while one of four animals infected after only two doses showed delayed onset of Ebola Virus Disease (EVD) and eventually succumbed to infection while the other three animals survived challenge. The monovalent MARV or SUDV vaccine candidates completely protected cynomolgus macaques from infection with lethal doses of MARV or SUDV. It was further demonstrated that combinations of MARV or SUDV with the EBOV vaccine can be formulated yielding bivalent vaccines retaining full efficacy. The recombinant subunit vaccine platform should therefore allow the development of a safe and efficacious multivalent vaccine candidate for protection against Ebola, Marburg and Sudan Virus Disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.703986","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T04:19:49Z","timestamp":1629260389000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":52,"title":["Recombinant Protein Filovirus Vaccines Protect Cynomolgus Macaques From Ebola, Sudan, and Marburg Viruses"],"prefix":"10.3389","volume":"12","author":[{"given":"Axel T.","family":"Lehrer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanore","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhuri","family":"Namekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin A.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri Ann S.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Lieberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Granados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Misamore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Yalley-Ogunro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan B.","family":"Geisbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle N.","family":"Agans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Cross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Geisbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medmal.2014.08.005","article-title":"Case Fatality Rates of Ebola Virus Diseases: A Meta-Analysis of World Health Organization Data","volume":"44","author":"Lefebvre","year":"2014","journal-title":"Med Mal Infect"},{"key":"B2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1093\/labmed\/lmy046","article-title":"Marburgviruses: An Update","volume":"50","author":"Miraglia","year":"2019","journal-title":"Lab Med"},{"key":"B3","unstructured":"World Health OrganizationEbola Virus Disease \u2013 Democratic Republic of the Congo2020"},{"key":"B4","unstructured":"CunninghamA\n          Science NewsIn a First, an Ebola Vaccine Wins Approval From the FDA2019"},{"key":"B5","unstructured":"McKeeS\n          US Approves Merck\u2019s Ebola Vaccine. PharmaTimes2019"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)32621-6","article-title":"Efficacy and Effectiveness of an rVSV-Vectored Vaccine in Preventing Ebola Virus Disease: Final Results From the Guinea Ring Vaccination, Open-Label, Cluster-Randomised Trial (Ebola \u00c7a Suffit!)","volume":"389","author":"Henao-Restrepo","year":"2017","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2020.09.011","article-title":"Preservation of Quaternary Structure in Thermostable, Lyophilized Filovirus Glycoprotein Vaccines: A Search for Stability-Indicating Assays","volume":"109","author":"Preston","year":"2020","journal-title":"J Pharm Sci"},{"key":"B8","unstructured":"EzeanolueE\n          Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.01.068","article-title":"Recombinant Proteins of Zaire Ebolavirus Induce Potent Humoral and Cellular Immune Responses and Protect Against Live Virus Infection in Mice","volume":"36","author":"Lehrer","year":"2018","journal-title":"Vaccine"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.06.035","article-title":"Recombinant Subunit Vaccines Protect Guinea Pigs From Lethal Ebola Virus Challenge","volume":"37","author":"Lehrer","year":"2019","journal-title":"Vaccine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2019.01.019","article-title":"Thermostable Ebola Virus Vaccine Formulations Lyophilized in the Presence of Aluminum Hydroxide","volume":"136","author":"Chisholm","year":"2019","journal-title":"Eur J Pharm Biopharm"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00576-17","article-title":"Recombinant Zika Virus Subunits Are Immunogenic and Efficacious in Mice","volume":"3","author":"To","year":"2018","journal-title":"mSphere"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007614","article-title":"Serological Evidence of Ebola Virus Exposure in Dogs From Affected Communities in Liberia: A Preliminary Report","volume":"13","author":"Haun","year":"2019","journal-title":"PloS neglected Trop Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131958","article-title":"Quadrivalent VesiculoVax Vaccine Protects Nonhuman Primates From Viral-Induced Hemorrhagic Fever and Death","volume":"130","author":"Cross","year":"2020","journal-title":"J Clin Invest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv284","article-title":"Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection","volume":"212","author":"Geisbert","year":"2015","journal-title":"J\u00a0Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2013.00267","article-title":"Animal Models for Ebola and Marburg Virus Infections","volume":"4","author":"Nakayama","year":"2013","journal-title":"Front Microbiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63591-2","article-title":"Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques: Evidence That Dendritic Cells Are Early and Sustained Targets of Infection","volume":"163","author":"Geisbert","year":"2003","journal-title":"Am J Pathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711250303","article-title":"The Pathology of Experimental Ebola Virus Infection in Monkeys","volume":"125","author":"Baskerville","year":"1978","journal-title":"J Pathol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15012-X","article-title":"Treatment of Ebola Virus Infection With a Recombinant Inhibitor of Factor VIIa\/tissue Factor: A Study in Rhesus Monkeys","volume":"362","author":"Geisbert","year":"2003","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"16142","DOI":"10.1038\/nmicrobiol.2016.142","article-title":"Rescue of Non-Human Primates From Advanced Sudan Ebolavirus Infection With Lipid Encapsulated siRNA","volume":"1","author":"Thi","year":"2016","journal-title":"Nat Microbiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1086\/520608","article-title":"Marburg Virus Angola Infection of Rhesus Macaques: Pathogenesis and Treatment With Recombinant Nematode Anticoagulant Protein C2","volume":"196","author":"Geisbert","year":"2007","journal-title":"J Infect Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv532","article-title":"Stability of a Vesicular Stomatitis Virus-Vectored Ebola Vaccine","volume":"213","author":"Arnemo","year":"2016","journal-title":"J Infect Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2018.06.001","article-title":"Stability and Suitability for Storage and Distribution of Ad26.ZEBOV\/MVA-BN\u00ae-Filo Heterologous Prime-Boost Ebola Vaccine","volume":"129","author":"Capelle","year":"2018","journal-title":"Eur J Pharm Biopharm"},{"key":"B24","first-page":"1942","volume-title":"Handbook of Biologically Active Peptides","author":"Kastin","year":"2013"},{"key":"B25","unstructured":"World Health OrganizationVaccine Safety Basics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(18)31710-0","article-title":"Prevention of Ebola Virus Disease Through Vaccination: Where We Are in 2018","volume":"392","author":"L\u00e9vy","year":"2018","journal-title":"Lancet"},{"key":"B27","volume-title":"HIV and AIDS Estimates West and Central Africa Unaids","year":"2019"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198703123161106","article-title":"Disseminated Vaccinia in a Military Recruit With Human Immunodeficiency Virus (HIV) Disease","volume":"316","author":"Redfield","year":"1987","journal-title":"New Engl J Med"},{"key":"B29","first-page":"1691","volume-title":"Plotkin\u2019s Vaccines","author":"Plotkin","year":"2018"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis592","article-title":"Pregnancy Modifies the Antibody Response to Trivalent Influenza Immunization","volume":"206","author":"Schlaudecker","year":"2012","journal-title":"J Infect Dis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2012.07.011","article-title":"The Safety of Adjuvants in Influenza Vaccines During Pregnancy: What do We Know and Why do We Need Them","volume":"207","author":"Jamieson","year":"2012","journal-title":"Am J obstetrics gynecol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3402\/gha.v7.25287","article-title":"The Interconnected and Cross-Border Nature of Risks Posed by Infectious Diseases","volume":"7","author":"Suk","year":"2014","journal-title":"Global Health Action"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00077-3","article-title":"Sequelae of Ebola Virus Disease: The Emergency Within the Emergency","volume":"16","author":"Vetter","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60179-9","article-title":"West African Ebola Crisis and Orphans","volume":"385","author":"Evans","year":"2015","journal-title":"Lancet"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.703986\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T04:20:22Z","timestamp":1629260422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.703986\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":34,"alternative-id":["10.3389\/fimmu.2021.703986"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.703986","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]},"article-number":"703986"}}