Biomimetic Apatite Nanoparticles and Microcrystalline Tyrosine as Biocompatible Vaccine Adjuvants: Performance in a...

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.