{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:03:27Z","timestamp":1785402207535,"version":"3.56.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100020098","name":"Innovative Health Initiative","doi-asserted-by":"publisher","award":["116068"],"award-info":[{"award-number":["116068"]}],"id":[{"id":"10.13039\/100020098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020098","name":"Innovative Health Initiative","doi-asserted-by":"publisher","award":["115842"],"award-info":[{"award-number":["115842"]}],"id":[{"id":"10.13039\/100020098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The recombinant vesicular stomatitis virus\u2013vectored Zaire Ebola virus glycoprotein (rVSV\u0394G-ZEBOV-GP) vaccine, while effective and well-tolerated, exhibits notable reactogenicity, manifesting in expected adverse events (AEs), such as fever, headache, and pain, along with rare, unexpected AEs, including skin lesions, cutaneous vasculitis, and transient arthritis. The presence or absence of AEs following rVSV\u0394G-ZEBOV-GP vaccination is associated with a specific innate plasma signature. This study aims to elucidate\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      the tropism of the vaccine for different cell types derived from tissues previously reported to be involved in the unexpected AEs. Upon\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      infection with rVSV\u0394G-ZEBOV-GP, various cell types, such as synoviocytes, fibroblasts, keratinocytes, and endothelial cells (except chondrocytes), demonstrate productive infection, which in dermal fibroblasts triggered the release of many innate plasma signature markers, including keratinocytes\u2019 pro-inflammatory and proapoptotic cytokines such as OSM and TRAIL. Infected monocytes from buffy coats, activated by infection, produce most innate plasma signature markers. In co-culture, rVSV\u0394G-ZEBOV-GP-infected monocytes serve as a source to synoviocyte infection, resulting in distinct kinetics modulation in innate biomarkers (transcription and secretion) and upregulation of specific genes, such as\n                      <jats:italic toggle=\"yes\">NEDD8<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SIGLEC-1<\/jats:italic>\n                      , which have been associated with inflammatory arthritis in animal models. Altogether, our work, based on\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      studies, provides insights into the possible mechanisms of rVSV\u0394G-ZEBOV-GP underlying the observed reactogenicity by showing tropism of the vaccine for off-target cells derived from AE-affected compartments (skin, joints, vessels). Furthermore,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      interaction with infected monocytes modulates the innate response of synoviocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Our study expanded knowledge about the cellular tropism of rVSV\u0394G-ZEBOV-GP vaccine toward peripheral blood mononuclear cells and cell lines derived from tissues (skin, vessels, and joints) associated with unexpected AEs, as well as their possible contribution to the vaccine-induced innate response. Using\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      infection and co-culture techniques, we showed that rVSV\u0394G-ZEBOV-GP-infected monocytes can transmit the virus to synoviocytes, and how infection affects human monocytes and synoviocytes at the protein and transcriptomic levels. Our findings provide insights into the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      off-target infection dynamics and innate immune response triggered by rVSV\u0394G-ZEBOV-GP vaccine. While these results may enhance understanding of rVSV-based vectors,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      relevance remains unclear, as does whether the effects come from the VSV backbone or Ebola GP. These findings support the evaluation of off-target effects of rVSV-based vaccine candidates, including those under development for hemorrhagic fever viruses, such as Marburg virus, Sudan virus, and Lassa virus, especially if similar AEs are observed.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00408-25","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T13:03:38Z","timestamp":1774357418000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>In vitro<\/i>\n                    cellular tropism and immunomodulatory response to rVSV\u0394G-ZEBOV-GP in human cells derived from tissues associated with adverse events"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0888-3867","authenticated-orcid":true,"given":"Paola","family":"Martinez-Murillo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4247-2837","authenticated-orcid":true,"given":"Catia","family":"Alvarez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3052-3518","authenticated-orcid":true,"given":"Francesco","family":"Santoro","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnologies, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Novedrati","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnologies, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sonnati","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnologies, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Montesi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnologies, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Lucchesi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnologies, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donata","family":"Medaglini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnologies, University of Siena","place":["Siena, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Eckerle","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire-Anne","family":"Siegrist","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"Center of Vaccinology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Geneva Medical School","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the VEBCON, VSV-EBOVAC, and VSV-EBOPLUS Consortia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"WHO. 2016. 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