Nanoparticles are excellent carriers for drug and protein, and have the potential to be used in vaccine delivery system. Here, we prepared different structures silica nanoparticles such as silica nanorattles (SNs), mesoporous silica nanoparticles (MSNs) and solid silica nanoparticles (SSNs), and chosen ovalbumin (OVA) as model protein to study the potential application of silica nanoparticles in protein vaccine delivery system. The results showed that silica nanoparticles were efficient in protein loading and dependent on structure, size and incubation medium. According to the three structure particles, SNs were favorable to be used as protein carriers. Furthermore, we proved low cytotoxicity of silica nanorattle on RAW 264.7 cell line and biocompatibility in vivo. In addition, SNs was capable to up-regulate the humoral immunity reaction when mice were vaccinated with SNs-OVA formulation. Taken together, SNs was excellent carriers for protein vaccine and has the potential to be used as adjuvant. (C) 2013 Elsevier Inc. All rights reserved.