{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:52:36Z","timestamp":1780411956341,"version":"3.54.1"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Lazio and Italian Ministry of research"},{"name":"Gates Foundation","award":["INV-059646 (ReiThera Srl)"],"award-info":[{"award-number":["INV-059646 (ReiThera Srl)"]}]},{"name":"Gates Foundation","award":["INV-008696"],"award-info":[{"award-number":["INV-008696"]}]},{"name":"Gates Foundation","award":["INV-064567 (Ragon Institute)"],"award-info":[{"award-number":["INV-064567 (Ragon Institute)"]}]},{"name":"Gates Foundation","award":["INV-007375"],"award-info":[{"award-number":["INV-007375"]}]},{"name":"Gates Foundation","award":["INV-065025 (IAVI)"],"award-info":[{"award-number":["INV-065025 (IAVI)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: The rapid development of safe and efficacious vaccines is often hindered by extensive, mandated non-clinical safety evaluations in animals. With the aim to provide scientific evidence supporting a \u201cvaccine platform approach\u201d, here we present the complete non-clinical studies for two investigational vaccines, GRAd-COV2 and GRAdHIVNE1, based on GRAd, a gorilla-derived group C adenoviral vector. Methods: The biodistribution of GRAd genomes following the intramuscular administration of the vaccines was assessed in rats by a sensitive qPCR method. Local tolerance and systemic toxic effects were evaluated in single- and repeated-dose toxicity studies in rabbits. Results: GRAd-COV2 and GRAdHIVNE1 were well-tolerated. Distribution was highly confined to the injection site and draining lymph nodes, and toxicity profile consisted of transient, non-adverse inflammatory responses, while the expected immune responses to the encoded antigens were successfully induced. Notably, both vaccines demonstrated a consistent safety profile despite transgene and backbone differences, comparable to other replication-defective adenoviral vectors. Conclusions: The established non-clinical safety profile of the GRAd platform provides a robust foundation for a more efficient and streamlined regulatory pathway. By leveraging this prior knowledge, future GRAd-based vaccines can achieve accelerated clinical development while fully adhering to the ethical principles of replacement, reduction, and refinement of animal use in research.<\/jats:p>","DOI":"10.3390\/vaccines14020157","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:33:50Z","timestamp":1770384830000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-Clinical Safety of GRAd Vector-Based COVID-19 and HIV Vaccines Supports a Platform Regulatory Approach"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0008-3475","authenticated-orcid":false,"given":"Reji","family":"Paalangara","sequence":"first","affiliation":[{"name":"International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Gohin","sequence":"additional","affiliation":[{"name":"Charles River Laboratories Evreux, 27930 Miserey, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Menard","sequence":"additional","affiliation":[{"name":"Charles River Laboratories Evreux, 27930 Miserey, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Amy","sequence":"additional","affiliation":[{"name":"Charles River Laboratories Evreux, 27930 Miserey, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahiba","family":"Berrabah","sequence":"additional","affiliation":[{"name":"Charles River Laboratories Evreux, 27930 Miserey, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rogue","sequence":"additional","affiliation":[{"name":"Charles River Laboratories Evreux, 27930 Miserey, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4172-2187","authenticated-orcid":false,"given":"Matthew A.","family":"Getz","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aljawharah","family":"Alrubayyi","sequence":"additional","affiliation":[{"name":"Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Battella","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6748-0307","authenticated-orcid":false,"given":"Angelo","family":"Raggioli","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Gentile","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthea","family":"Di Rita","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Noto","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Miselli","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Grazioli","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Napolitano","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhurata","family":"Sowcik","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-5844","authenticated-orcid":false,"given":"Marco","family":"Soriani","sequence":"additional","affiliation":[{"name":"ReiThera Srl, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4470-218X","authenticated-orcid":false,"given":"Benjamin","family":"Chmielewski","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lebohang","family":"Molife","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-3999","authenticated-orcid":false,"given":"Vincent","family":"Muturi-Kioi","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative (IAVI), New York, NY 10004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-1470","authenticated-orcid":false,"given":"Azure Tariro","family":"Makadzange","sequence":"additional","affiliation":[{"name":"Mutala Trust, Harare, Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6875-4472","authenticated-orcid":false,"given":"Gaurav D.","family":"Gaiha","sequence":"additional","affiliation":[{"name":"Ragon 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