162449 20251017144644.0 doi 10.1021/acsami.5c10402 sideral 145020 ART-2025-145020 eng Pérez, Estela Biomimetic apatite nanoparticles and microcrystalline tyrosine as biocompatible vaccine adjuvants: performance in a bluetongue virus sheep model 2025 Access copy available to the general public Unrestricted Aluminum oxyhydroxide (AlOOH) is the most widely used vaccine adjuvant, but its known adverse effects prompt the finding of other, safer alternative adjuvants. This study compares in sheep the global performance and safety of vaccine prototypes against bluetongue virus (BTV) formulated with AlOOH, biomimetic apatite nanoparticles (ApNPs), and microcrystalline tyrosine (MCT). Five groups of 6 sheep were included in the study: control, BTV serotype 4 alone, and BTV-4 combined either with AlOOH, ApNPs, or MCT. Adjuvants were fully characterized. Group specific antibodies against BTV-4 were observed in all treatment groups, including BTV-4 alone. After booster inoculation, ApNPs or MCT groups responded immediately, and it was delayed for BTV-4 and AlOOH groups. Comparable neutralizing antibody responses were observed in all treatment groups but were earlier for BTV-4, ApNPs, and MCT groups when compared with the AlOOH group. No significant systemic alterations were observed during the study. The AlOOH group developed more pronounced local reactions that persisted throughout the 133-day study and were evident as post-mortem granulomas. ApNPs and MCT are biocompatible, safer, and viable alternative adjuvants for sheep vaccines. BTV alone might also be suitable for this purpose. This work is the first demonstrating the suitability of biocompatible alternative adjuvants in sheep vaccines. info:eu-repo/grantAgreement/ES/MICINN/CEX2023-001286-S info:eu-repo/grantAgreement/ES/MICINN/PID2021-127847OB-I00 info:eu-repo/grantAgreement/ES/MICINN/RTI2018-096172-B-C33 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sebastián, Víctor Universidad de Zaragoza (orcid)0000-0002-6873-5244 Rodríguez-Largo, Ana (orcid)0000-0002-2685-1730 de Miguel, Ricardo Gómez, Álex Universidad de Zaragoza (orcid)0000-0002-9723-9004 Kramer, Matthias F. Graessel, Anke Parra-Torrejón, Belén Delgado-López, José Manuel Utrilla-Trigo, Sergio Jiménez-Cabello, Luis Ortego, Javier de Blas, Ignacio Universidad de Zaragoza (orcid)0000-0002-1204-4356 Reina, Ramsés Pérez, Marta Luján, Lluís Universidad de Zaragoza (orcid)0000-0002-2053-9842 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 17, 32 (2025), 45538-45554 ACS appl. mater. interfaces ACS applied materials & interfaces 1944-8244 15491428 http://zaguan.unizar.es/record/162449/files/texto_completo.pdf Versión publicada 3168554 http://zaguan.unizar.es/record/162449/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:162449 articulos driver 2025-10-17-14:33:25 ARTICLE