Versatile Functionalization of Ferritin Nanoparticles by Intein-Mediated Trans-Splicing for Antigen/Adjuvant Co-delivery

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Abstract
Self-assembling protein nanoparticles are extensively and increasingly engineered to integrate adjuvants with antigens to elicit potent and long-term immunity due to uniform architecture, inherent biocompatibility and excellent plasticity. However, functionalization of nanoparticles by surface tailoring has two common problems: (1) disassembly caused by loaded cargoes; and (2) inconvenient to co-deliver adjuvant with antigen by genetic fusion. Here, we report an intein-mediated trans-splicing approach that overcomes the detrimental effects of loaded proteins on ferritin nanoparticle stability, and allows concurrent display of antigen and adjuvant in a facile, efficient and site-specific manner. An immunization study with epitope-based model antigen reveals that antigen and adjuvant co-delivery nanoparticles induce most potent protective immunity than other formulations. Our results demonstrate that protein engineering represents an intriguing approach for antigen/adjuvant co-delivery to potentiate antigen-associated immune responses.
Funding Information
  • Ministry of Science and Technology of the People's Republic of China (2016YFA0502101)
  • National Natural Science Foundation of China (81371826, 31570169, 31300148, 81572002)
  • the Chinese Academy of Sciences ?100 Talents? program (Y214P1109)

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