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This study evaluated the immunogenicity and safety of novel inactivated RVF vaccines in sheep, enhanced with zinc oxide nanoparticles (ZnNPs) and selenium nanoparticles (SeNPs) as co-adjuvants, compared to an aluminum hydroxide gel (ALHV) adjuvanted vaccine alone. Our findings demonstrate that nanoparticle-formulated ALHV elicited a markedly faster onset of protection, achieving protective neutralizing antibody titers within 3\u20134 days post-vaccination, significantly accelerating immunity compared to approximately two weeks with ALHV alone. Furthermore, these enhanced formulations induced more robust and sustained humoral and IFN-\u03b3 responses, indicating superior activation of both antibody-mediated and cell-mediated immunity. The nanoparticle-enhanced vaccines also maintained long-lasting protection, extending the duration of protective antibody titers up to 11 months, compared to 10 months for ALHV alone. Beyond immunological benefits, these vaccines were safe, stable, and associated with improved growth performance in vaccinated sheep, particularly with ZnNPs. Biochemical analyses confirmed the absence of adverse effects on liver and kidney function, while showing beneficial increases in total protein and globulin levels. This study underscores the potential of SeNPs and ZnNPs as potent adjuvants for inactivated RVF vaccines, offering a promising strategy for developing more effective, rapidly protective, and durable vaccines against RVF and potentially other zoonotic diseases.<\/jats:p>","DOI":"10.1007\/s11250-025-04783-z","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T10:51:21Z","timestamp":1766573481000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ZnNPs and senps co-adjuvants deliver superior and long-lasting protection: first report in inactivated Rift Valley fever vaccines for sheep"],"prefix":"10.1007","volume":"58","author":[{"given":"Sally Zaki Abdelrahman","family":"Hafez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel Abdelazim","family":"Fayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taradi Abdelfattah","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany Dieb","family":"Bahr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"Kamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"4783_CR1","first-page":"22","volume":"5","author":"E Abd","year":"2020","unstructured":"Abd E, Rahman SE, Abul Magd DM, Atwa MH, Soliman SM (2020) Evaluation of cellular and humeral immune response of sheep vaccinated with inactivated rift Valley fever vaccine adjuvanted with Montanide gel. 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