{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:15:33Z","timestamp":1792181733518,"version":"4.4.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Janssen Vaccines & Prevention B.V."},{"name":"National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services","award":["HHSN272200800056C"],"award-info":[{"award-number":["HHSN272200800056C"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Though clinically similar, Ebola virus disease and Marburg virus disease are caused by different viruses. Of the 30 documented outbreaks of these diseases in sub-Saharan Africa, eight were major outbreaks (\u2265200 cases; five caused by <jats:italic>Zaire ebolavirus<\/jats:italic> [EBOV], two by <jats:italic>Sudan ebolavirus<\/jats:italic> [SUDV], and one by <jats:italic>Marburg virus<\/jats:italic> [MARV]). Our purpose is to develop a multivalent vaccine regimen protecting against each of these filoviruses. This first-in-human study assessed the safety and immunogenicity of several multivalent two-dose vaccine regimens that contain Ad26.Filo and MVA-BN-Filo.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Ad26.Filo combines three vaccines encoding the glycoprotein (GP) of EBOV, SUDV, and MARV. MVA-BN-Filo is a multivalent vector encoding EBOV, SUDV, and MARV GPs, and Ta\u00ef Forest nucleoprotein. This Phase 1, randomized, double-blind, placebo-controlled study enrolled healthy adults (18\u201350 years) into four groups, randomized 5:1 (active:placebo), to assess different Ad26.Filo and MVA-BN-Filo vaccine directionality and administration intervals. The primary endpoint was safety; immune responses against EBOV, SUDV, and MARV GPs were also assessed.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Seventy-two participants were randomized, and 60 (83.3%) completed the study. All regimens were well tolerated with no deaths or vaccine-related serious adverse events (AEs). The most frequently reported solicited local AE was injection site pain\/tenderness. Solicited systemic AEs most frequently reported were headache, fatigue, chills, and myalgia; most solicited AEs were Grade 1\u20132. Solicited\/unsolicited AE profiles were similar between regimens. Twenty-one days post-dose 2, 100% of participants on active regimen responded to vaccination and exhibited binding antibodies against EBOV, SUDV, and MARV GPs; neutralizing antibody responses were robust against EBOV (85.7\u2013100%), but lower against SUDV (35.7\u2013100%) and MARV (0\u201357.1%) GPs. An Ad26.Filo booster induced a rapid further increase in humoral responses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study demonstrates that heterologous two-dose vaccine regimens with Ad26.Filo and MVA-BN-Filo are well tolerated and immunogenic in healthy adults.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>ClinicalTrials.gov<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02860650\" xlink:type=\"simple\">NCT02860650<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0274906","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T17:27:47Z","timestamp":1664990867000},"page":"e0274906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["First-in-human study to evaluate safety, tolerability, and immunogenicity of heterologous regimens using the multivalent filovirus vaccines Ad26.Filo and MVA-BN-Filo administered in different sequences and schedules: A randomized, controlled study"],"prefix":"10.1371","volume":"17","author":[{"given":"Viki","family":"Bockstal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgi","family":"Shukarev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3548-3482","authenticated-orcid":true,"given":"Chelsea","family":"McLean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Bart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auguste","family":"Gaddah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickson","family":"Anumenden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen N.","family":"Stoop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Marit de Groot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G.","family":"Pau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Hendriks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"De Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen W.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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